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Sample records for b-cell lymphoblastic lymphoma

  1. Primary lymphoblastic B-cell lymphoma of the stomach: A case report

    Institute of Scientific and Technical Information of China (English)

    Miao-Xia He; Ming-Hua Zhu; Wei-Qiang Liu; Li-Li Wu; Xiong-Zeng Zhu

    2008-01-01

    Primary stomach lymphoblastic B-cell lymphoma (B-LBL) is a rare tumor. We describe a primary stomach B-LBL in a 38 years old female who presented with nonspecific complaints of fatigue and vomiting for 2 mo.Gastrofiberscopy revealed a large gastric ulcer, which was successfully resected. Pathology showed a lymphoblastic cell lymphoma arising from the stomach, and there was no evidence of disease at any extrastomach site.Immunohistochemical staining and gene rearrangement studies supported that the stomach tumor was a clonal B-cell lymphoma. Therefore, the diagnosis of B-LBL was made based on the stomach specimen.

  2. Acute kidney injury and bilateral symmetrical enlargement of the kidneys as first presentation of B-cell lymphoblastic lymphoma.

    Science.gov (United States)

    Shi, Su-fang; Zhou, Fu-de; Zou, Wan-zhong; Wang, Hai-yan

    2012-12-01

    Lymphoblastic lymphoma is an uncommon subtype of lymphoid neoplasm in adults. Acute kidney injury at initial presentation due to lymphoblastic lymphoma infiltration of the kidneys has rarely been described. We report a 19-year-old woman who presented with acute kidney injury due to massive lymphomatous infiltration of the kidneys. The diagnosis of B-cell lymphoblastic lymphoma was established by immunohistochemical study of the biopsied kidney. The patient had an excellent response to the VDCLP protocol (vincristine, daunomycin, cyclophosphamide, asparaginase, and dexamethasone) with sustained remission. We recommend that lymphomatous infiltration be considered in patients presenting with unexplained acute kidney injury and enlarged kidneys.

  3. SLP65 deficiency results in perpetual V(D)J recombinase activity in pre-B-lymphoblastic leukemia and B-cell lymphoma cells.

    Science.gov (United States)

    Sprangers, M; Feldhahn, N; Liedtke, S; Jumaa, H; Siebert, R; Müschen, M

    2006-08-24

    Perpetual V(D)J recombinase activity involving multiple DNA double-strand break events in B-cell lineage leukemia and lymphoma cells may introduce secondary genetic aberrations leading towards malignant progression. Here, we investigated defective negative feedback signaling through the (pre-) B-cell receptor as a possible reason for deregulated V(D)J recombinase activity in B-cell malignancy. On studying 28 cases of pre-B-lymphoblastic leukemia and 27 B-cell lymphomas, expression of the (pre-) B-cell receptor-related linker molecule SLP65 (SH2 domain-containing lymphocyte protein of 65 kDa) was found to be defective in seven and five cases, respectively. SLP65 deficiency correlates with RAG1/2 expression and unremitting V(H) gene rearrangement activity. Reconstitution of SLP65 expression in SLP65-deficient leukemia and lymphoma cells results in downregulation of RAG1/2 expression and prevents both de novo V(H)-DJ(H) rearrangements and secondary V(H) replacement. We conclude that iterative V(H) gene rearrangement represents a frequent feature in B-lymphoid malignancy, which can be attributed to SLP65 deficiency in many cases.

  4. Intravascular large B cell lymphoma

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    Ricardo García-Muñoz

    2014-01-01

    Full Text Available Intravascular large B cell lymphoma (IVBCL is a rare type of extranodal large B cell lymphoma characterized by selective growth of lymphoma cells within the microvasculature. We present an illustrative case of intravascular B cell lymphoma suspected by the presence of a very small monoclonal B cell population identified by immunophenotype and polymerase chain reaction in bone marrow. The diagnosis was confirmed by skin biopsy.

  5. Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma

    Science.gov (United States)

    2015-11-23

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  6. 皮肤原发性B淋巴母细胞淋巴瘤一例%A case of primary cutaneous B-cell lymphoblastic lymphoma

    Institute of Scientific and Technical Information of China (English)

    曲延刚; 唐爱萍; 王红莉; 李虹; 陈甦

    2013-01-01

    A 56-year old man developed a raised nodule on the left forearm half a year before 2006,which gradually enlarged.Skin examination revealed a mass measuring 3 cm in diameter at the extensor aspect of left forearm,which was fixed,slightly deep-colored,adherent to the skin with an unclear margin.There was a postoperative scar measuring 2.5 cm in length.Histopathological examination revealed small-to mediumsized round or oval lymphocytes with fine chromatin,unclear nucleoli,a small amount of lightly stained cytoplasm.Immunophenotype analysis showed that the tumor cells were positive for terminal deoxynucleotidyl transferase (TDT),leucocyte common antigen (LCA),PAX5 (paired box 5),C D79a,CD10,Ki-67 (50%),but negative for CD20,CD3,CD30,epithelial membrane antigen (EMA),CD5,CD23 and CD56.He was pathologically diagnosed with cutaneous B-cell lymphoblastic lymphoma,and given combination chemotherapy with cyclophosphamide,doxorubicin,vincristine and prednisone.Unfortunately,the condition was poorly controlled,and the patient died 4 years and 9 months later.%患者男,56岁.2006年发现左前臂隆起性结节半年,渐增大.皮肤科检查:左前臂外侧可见一直径3 cm的肿物,其皮肤表面颜色略深,可见手术瘢痕长2.5 cm,肿物与皮肤粘连,固定,边界不清.组织病理学检查:瘤细胞圆形、卵圆形,小至中等大的淋巴母细胞,染色质细腻,核仁不明显,胞质少而淡染,弥漫分布.免疫组化:末端脱氧核苷酸转移酶(TDT)+、LCA+、CD20-、CD79a+、转录因子PAX5+、CD3-、CD30-、Ki-67阳性细胞数50%、上皮膜抗原(EMA)-、CD5-、CD10+、CD23-、CD56-.病理诊断:皮肤B淋巴母细胞淋巴瘤.治疗:给予环磷酰胺+多柔比星+长春新碱+泼尼松(CHOP)方案化疗,病情反复,随访4年9个月时患者死亡.

  7. Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

    Science.gov (United States)

    2016-07-12

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  8. Primary Hepatosplenic Large B-Cell Lymphoma

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    M.R. Morales-Polanco

    2008-03-01

    Full Text Available Diffuse large B-cell lymphoma is the most common form of lymphoma. It usually begins in the lymph nodes; up to 40% may have an extranodal presentation. According to a definition of primary extranodal lymphoma with presentation only in extranodal sites, there are reports of large B-cell lymphomas limited to liver or spleen as separate entities, and to date there have been only three documented cases of primary hepatosplenic presentation. This paper reports a fourth case. Due to a review of the literature and the clinical course of the case reported, we conclude that primary hepatosplenic large B-cell lymphoma has been found predominantly in females older than 60 years. The patients reported had <2 months of evolution prior to diagnosis, prominent B symptoms, splenomegaly in three and hepatomegaly in two, none with lymph node involvement. All had thrombocytopenia and abnormal liver function tests; three had anemia and elevated serum lactic dehydrogenase levels, two with hemophagocytosis in bone marrow. Because of the previously mentioned data, it can be stated that primary hepatosplenic lymphoma is an uncommon and aggressive form of disease that requires immediate recognition and treatment.

  9. Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T Cells for B-cell Leukemia/Lymphoma

    Science.gov (United States)

    2016-08-22

    Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  10. Intravascular Large B-Cell Lymphoma

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    Maria S. Khan MD, FACP

    2014-03-01

    Full Text Available Case Presentation. A 69-year-old Hispanic male, with a past history of diabetes and coronary disease, was admitted for fever, diarrhea, and confusion of 4 weeks duration. Physical examination showed a disoriented patient with multiple ecchymoses, possible ascites, and bilateral scrotal swelling. Hemoglobin was 6.7, prothrombin time (PT 21.4 seconds with international normalized ratio 2.1, partial thromboplastin time (PTT 55.6 seconds, fibrin split 10 µg/L, and lactate dehydrogenase (LDH 1231 IU/L. Except for a positive DNA test for Epstein–Barr virus (EBV infection, extensive diagnostic workup for infections, malignancy, or a neurological cause was negative. Mixing studies revealed a nonspecific inhibitor of PT and PTT but Factor VIII levels were normal. The patient was empirically treated with antibiotics but developed hypotension and died on day 27 of admission. At autopsy, patient was found to have intravascular diffuse large B-cell lymphoma involving skin, testes, lung, and muscles. The malignant cells were positive for CD20, CD791, Mum-1, and Pax-5 and negative for CD3, CD5, CD10, CD30, and Bcl-6. The malignant cells were 100% positive for Ki-67. Discussion. Intravascular large cell B-cell lymphoma (IVLBCL is rare form of diffuse large B-cell lymphoma and tends to proliferate within small blood vessels, particularly capillaries and postcapillary venules. The cause of its affinity for vascular bed remains unknown. In many reports, IVLBCL was associated with HIV, HHV8, and EBV infections. The fact that our case showed evidence of EBV infection lends support to the association of this diagnosis to viral illness. The available literature on this subject is scant, and in many cases, the diagnosis was made only at autopsy. The typical presentation of this disorder is with B symptoms, progressive neurologic deficits, and skin findings. Bone marrow, spleen, and liver are involved in a minority of patients. Nearly all patients have elevated LDH

  11. Primary marginal zone B-cell lymphoma of appendix

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    Radha S

    2008-07-01

    Full Text Available Primary lymphomas of appendix are extremely rare tumors. The first case of primary lymphoma of appendix was reported by Warren in the year 1898. Incidence of primary lymphoma of appendix is 0.015% of all gastrointestinal lymphomas. This is a report of primary marginal zone B-cell lymphoma of appendix which presented as appendicular mass. As some cases are incidentally discovered, this case emphasizes that histological examination of all appendicectomy specimens is mandatory.

  12. Genetic alterations in B-cell non-Hodgkin's lymphoma

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    Magić Zvonko

    2005-01-01

    Full Text Available Background. Although the patients with diagnosed B-NHL are classified into the same disease stage on the basis of clinical, histopathological, and immunological parameters, they respond significantly different to the applied treatment. This points out the possibility that within the same group of lymphoma there are different diseases at molecular level. For that reason many studies deal with the detection of gene alterations in lymphomas to provide a better framework for diagnosis and treatment of these hematological malignancies. Aim. To define genetic alterations in the B-NHL with highest possibilities for diagnostic purposes and molecular detection of MRD. Methods. Formalin fixed and paraffin embedded lymph node tissues from 45 patients were examined by different PCR techniques for the presence of IgH and TCR γ gene rearrangement; K-ras and H-ras mutations; c-myc amplification and bcl-2 translocation. There were 34 cases of B-cell non-Hodgkin’s lymphoma (B-NHL, 5 cases of T-cell non-Hodgkin’s lymphoma (T-NHL and 6 cases of chronic lymphadenitis (CL. The mononuclear cell fraction of the peripheral blood of 12 patients with B-NHL was analyzed for the presence of monoclonality at the time of diagnosis and in 3 to 6 months time intervals after an autologous bone marrow transplantation (BMT. Results. The monoclonality of B-lymphocytes, as evidenced by DNA fragment length homogeneity, was detected in 88 % (30/34 of B-NHL, but never in CL, T-NHL, or in normal PBL. Bcl-2 translocation was detected in 7/31 (22.6% B-NHL specimens, c-myc amplification 9/31 (29%, all were more than doubled, K-ras mutations in 1/31 (3.23% and H-ras mutations in 2/31 (6.45% of the examined B-NHL samples. In the case of LC and normal PBL, however, these gene alterations were not detected. All the patients (12 with B-NHL had dominant clone of B-lymphocyte in the peripheral blood at the time of diagnosis while only in 2 of 12 patients MRD was detected 3 or 6 months after

  13. Mediastinal involvement in adults with lymphoblastic lymphoma

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    Schwartz, E.E.; Conroy, J.F.; Bonner, H.

    Radiologic, clinical, and pathologic findings are described in 6 young adults with lymphoblastic lymphoma (LBL), an aggressive tumor which has recently become recognized as a serious threat to adults as well as to children. Each patient presented with a mediastinal mass, three of them developing cardiac tamponade and one a superior vena cava syndrome. CT scanning and echocardiography were particularly helpful in defining the lesions. The rapid dissemination of LBL, and its early progression to a leukemic phase call for promt diagnosis and treatment.

  14. Novel Therapies for Aggressive B-Cell Lymphoma

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    Kenneth A. Foon

    2012-01-01

    Full Text Available Aggressive B-cell lymphoma (BCL comprises a heterogeneous group of malignancies, including diffuse large B-cell lymphoma (DLBCL, Burkitt lymphoma, and mantle cell lymphoma (MCL. DLBCL, with its 3 subtypes, is the most common type of lymphoma. Advances in chemoimmunotherapy have substantially improved disease control. However, depending on the subtype, patients with DLBCL still exhibit substantially different survival rates. In MCL, a mature B-cell lymphoma, the addition of rituximab to conventional chemotherapy regimens has increased response rates, but not survival. Burkitt lymphoma, the most aggressive BCL, is characterized by a high proliferative index and requires more intensive chemotherapy regimens than DLBCL. Hence, there is a need for more effective therapies for all three diseases. Increased understanding of the molecular features of aggressive BCL has led to the development of a range of novel therapies, many of which target the tumor in a tailored manner and are summarized in this paper.

  15. Obinutuzumab, Venetoclax, and Lenalidomide in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-03-01

    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  16. Ibrutinib Before and After Stem Cell Transplant in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

    Science.gov (United States)

    2016-10-20

    Activated B-Cell-Like Diffuse Large B-Cell Lymphoma; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  17. Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas

    Science.gov (United States)

    2017-03-13

    Activated B-Cell-Like Diffuse Large B-Cell Lymphoma; ALK-Positive Large B-Cell Lymphoma; Atypical Burkitt/Burkitt-Like Lymphoma; Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Epstein-Barr Virus Positive Diffuse Large B-Cell Lymphoma of the Elderly; Epstein-Barr Virus-Positive Mucocutaneous Ulcer; Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma; High-Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements; Human Herpesvirus-8-Positive Neoplastic Cells Present; Intravascular Large B-Cell Lymphoma; MYC-Negative B-Cell Lymphoma With 11q Aberration Resembling Burkitt Lymphoma; Plasmablastic Lymphoma; Primary Cutaneous Diffuse Large B-Cell Lymphoma; Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Primary Effusion Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Lymphomatoid Granulomatosis; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Skin Ulcer; Small Intestinal B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

  18. Sinonasal Lymphoma Presenting as a Probable Sanctuary Site for Relapsed B Acute Lymphoblastic Leukaemia: A Case Report and Review of the Literature

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    W. Y. Lim

    2015-01-01

    Full Text Available Sinonasal lymphoma is a non-Hodgkin lymphoma (NHL representing 1.5% of all lymphomas. It presents as an unremitting ulceration with progressive destruction of midline sinonasal and surrounding structures. Poor prognosis warrants early treatment although diagnosis is challenging and frequently delayed. It is usually primary in origin and to our knowledge the sinonasal region has never been reported as a sanctuary site in leukaemia/lymphoma relapse. We present a unique case of B-cell ALL (acute lymphoblastic leukaemia with late relapse to the nasal septum as a sinonasal lymphoblastic lymphoma and with genetic support for this as a sanctuary site.

  19. Profiling of diffuse large B-cell lymphoma by immunohistochemistry

    DEFF Research Database (Denmark)

    Sjö, Lene Dissing; Poulsen, Christian Bjørn; Hansen, Mads;

    2007-01-01

    Diffuse large B-cell lymphoma (DLBCL) is a frequent lymphoma subtype with a heterogeneous behavior and a variable response to conventional chemotherapy. This clinical diversity is believed to reflect differences in the molecular pathways leading to lymphomagenesis. In this study, we have analyzed...

  20. New B-cell Lymphomas in the Setting of a Previous Rare Breast Implant–Associated B-cell Lymphoma

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    Messer, Alison; Wang, Wei; Duvic, Madeleine

    2016-01-01

    Summary: We present a follow-up of a patient who underwent right-sided subtotal mastectomy and placement of right-sided saline implant in 1968 for a phyllodes tumor and then in 2012 was diagnosed with a rare B-cell type lymphoma of the right breast. In 2015, she was diagnosed with diffuse large B-cell lymphoma involvement of the left breast and left leg and experienced subsequent self-regression of leg lesions without therapy. PMID:27975038

  1. Microenvironment-Centred Dynamics in Aggressive B-Cell Lymphomas

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    Matilde Cacciatore

    2012-01-01

    Full Text Available Aggressive B-cell lymphomas share high proliferative and invasive attitudes and dismal prognosis despite heterogeneous biological features. In the interchained sequence of events leading to cancer progression, neoplastic clone-intrinsic molecular events play a major role. Nevertheless, microenvironment-related cues have progressively come into focus as true determinants for this process. The cancer-associated microenvironment is a complex network of nonneoplastic immune and stromal cells embedded in extracellular components, giving rise to a multifarious crosstalk with neoplastic cells towards the induction of a supportive milieu. The immunological and stromal microenvironments have been classically regarded as essential partners of indolent lymphomas, while considered mainly negligible in the setting of aggressive B-cell lymphomas that, by their nature, are less reliant on external stimuli. By this paper we try to delineate the cardinal microenvironment-centred dynamics exerting an influence over lymphoid clone progression in aggressive B-cell lymphomas.

  2. Primary Testicular B-cell Lymphoma

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    Aykut Buğra Şentürk

    2015-12-01

    Full Text Available Primary testicular lymphoma constitutes only 1-7% of all testicular neoplasms and less than 1% of all non-Hodgkin lymphoma. We report a 69-year-old man who presented with a painful right testicular mass. Treatment modalities consist of surgical excision, chemotherapy and radiation therapy, however there are no standardized treatment options.

  3. The spectrum of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a description of 10 cases.

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    Gualco, Gabriela; Natkunam, Yasodha; Bacchi, Carlos E

    2012-05-01

    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, is a diagnostic provisional category in the World Health Organization (WHO) 2008 classification of lymphomas. This category was designed as a measure to accommodate borderline cases that cannot be reliably classified into a single distinct disease entity after all available morphological, immunophenotypical and molecular studies have been performed. Typically, these cases share features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, or include characteristics of both lymphomas. The rarity of such cases poses a tremendous challenge to both pathologists and oncologists because its differential diagnosis has direct implications for management strategies. In this study, we present 10 cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma and have organized the criteria described by the WHO into four patterns along with detailed clinical, morphological and immunophenotypic characterization and outcome data. Our findings show a male preponderance, median age of 37 years and a mediastinal presentation in 80% of cases. All cases expressed at least two markers associated with B-cell lineage and good response to combination chemotherapy currently employed for non-Hodgkin lymphomas.

  4. Lenalidomide in Diffuse Large B-Cell Lymphoma

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    Catherine Thieblemont; Marie-Hélène Delfau-Larue; Bertrand Coiffier

    2012-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma (NHL) in adults. Even if the natural history of DLBCL has been improved with the advent of immunochemotherapy, the survival results obtained with current treatment options clearly indicate that new agents or novel approaches are needed. Lenalidomide (Revlimid, Celgene Corporation, Summit, NJ, USA), an analogue of thalidomide, is an immunomodulatory drug with pleiotropic mechanisms of action potentially add...

  5. High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

    Science.gov (United States)

    2016-07-08

    Post-Transplant Lymphoproliferative Disorder; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  6. Lack of TERT Promoter Mutations in Human B-Cell Non-Hodgkin Lymphoma

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    Gary Lam

    2016-10-01

    Full Text Available Non-Hodgkin lymphomas (NHL are a heterogeneous group of immune cell neoplasms that comprise molecularly distinct lymphoma subtypes. Recent work has identified high frequency promoter point mutations in the telomerase reverse transcriptase (TERT gene of different cancer types, including melanoma, glioma, liver and bladder cancer. TERT promoter mutations appear to correlate with increased TERT expression and telomerase activity in these cancers. In contrast, breast, pancreatic, and prostate cancer rarely demonstrate mutations in this region of the gene. TERT promoter mutation prevalence in NHL has not been thoroughly tested thus far. We screened 105 B-cell lymphoid malignancies encompassing nine NHL subtypes and acute lymphoblastic leukemia, for TERT promoter mutations. Our results suggest that TERT promoter mutations are rare or absent in most NHL. Thus, the classical TERT promoter mutations may not play a major oncogenic role in TERT expression and telomerase activation in NHL.

  7. Lack of TERT Promoter Mutations in Human B-Cell Non-Hodgkin Lymphoma

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    Lam, Gary; Xian, Rena R.; Li, Yingying; Burns, Kathleen H.; Beemon, Karen L.

    2016-01-01

    Non-Hodgkin lymphomas (NHL) are a heterogeneous group of immune cell neoplasms that comprise molecularly distinct lymphoma subtypes. Recent work has identified high frequency promoter point mutations in the telomerase reverse transcriptase (TERT) gene of different cancer types, including melanoma, glioma, liver and bladder cancer. TERT promoter mutations appear to correlate with increased TERT expression and telomerase activity in these cancers. In contrast, breast, pancreatic, and prostate cancer rarely demonstrate mutations in this region of the gene. TERT promoter mutation prevalence in NHL has not been thoroughly tested thus far. We screened 105 B-cell lymphoid malignancies encompassing nine NHL subtypes and acute lymphoblastic leukemia, for TERT promoter mutations. Our results suggest that TERT promoter mutations are rare or absent in most NHL. Thus, the classical TERT promoter mutations may not play a major oncogenic role in TERT expression and telomerase activation in NHL. PMID:27792139

  8. Prognostic Assessment in Patients with Indolent B-Cell Lymphomas

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    Luca Arcaini

    2012-01-01

    Full Text Available Follicular lymphoma (FL is an indolent lymphoma with long median survival. Many studies have been performed to build up prognostic scores potentially useful to identify patients with poorer outcome. In 2004, an international consortium coordinated by the International Follicular Lymphoma Prognostic Factor project was established and a new prognostic study was launched (FLIPI2 using progression-free survival (PFS as main endpoint and integrating all the modern parameters prospectively collected. Low-grade non-Hodgkin lymphomas were once considered as a heterogenous group of lymphomas characterized by an indolent clinical course. Each entity is characterized by unique clinicobiologic features. Some studies have been focused on prognostic factors in single lymphoma subtypes, with the development of specific-entity scores based on retrospective series, for instance splenic marginal zone lymphoma (SMZL. A widely accepted prognostic tool for clinical usage for indolent non-follicular B-cell lymphomas is largely awaited. In this paper we summarized the current evidence regarding prognostic assessment of indolent follicular and non-follicular lymphomas.

  9. B cell lymphomas express CX3CR1 a non-B cell lineage adhesion molecule

    DEFF Research Database (Denmark)

    Andreasson, U.; Ek, S.; Merz, H.

    2008-01-01

    To study the differential expression of cell membrane-bound receptors and their potential role in growth and/or survival of the tumor cells, highly purified follicular lymphoma cells were analyzed, using gene expression analysis, and compared to non-malignant B cell populations. Filtering...... the genome for overexpressed genes coding for cell membrane-bound proteins/receptors resulted in a hit list of 27 identified genes. Among these, we have focused on the aberrant over expression of CX3CR1, in different types of B cell lymphoma, as compared to non-malignant B cells. We show that CX3CR1, which...... normally is not expressed on B cells, is expressed both at the mRNA and protein level in several subtypes of lymphoma. CX3CR1 has also shown to be involved in the homing to specific tissues that express the ligand, CX3CL1, in breast and prostate cancer and may thus be involved in dissemination of lymphoma...

  10. Immune Thrombocytopenia in a Child with T Cell Lymphoblastic Lymphoma

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    Kayo Tokeji

    2016-01-01

    Full Text Available We describe the case of a 13-year-old boy who presented with persistent thrombocytopenia during maintenance chemotherapy with mercaptopurine and methotrexate for T cell lymphoblastic lymphoma. He was diagnosed with immune thrombocytopenia (ITP after thorough investigations for the relapse of lymphoma and was successfully treated with immunoglobulin and steroids. ITP is known to be associated with chronic lymphocytic leukemia, Hodgkin lymphoma, and various types of non-Hodgkin lymphoma but rarely with T cell non-Hodgkin lymphoma or in children. Diagnosis of ITP with lymphoma is challenging due to the many factors affecting platelet counts, and ITP often complicates the diagnosis or treatment course of lymphoma. The underlying mechanism of ITP with NHL is still unclear. Drug-induced immunomodulation with a reduction of regulatory T cells might have contributed to the development of ITP in our case.

  11. Anthropometrics and Prognosis in Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    Bendtsen, Mette Dahl; Munksgaard, Peter Svenssen; Severinsen, Marianne Tang;

    2016-01-01

    OBJECTIVE: The impact of body mass index (BMI) and body surface area (BSA) on survival in diffuse large B-cell lymphoma (DLBCL) is controversial. Recent studies show superior outcomes for overweight and obese patients. PATIENTS AND METHODS: 653 R-CHOP(-like) treated DLBCL patients were included...

  12. Diffuse Large B Cell Lymphoma Mimicking Granulomatosis with Polyangiitis

    Directory of Open Access Journals (Sweden)

    Mohammad E. Naffaa

    2016-01-01

    Full Text Available In a patient with systemic multiorgan disease with overlapping features, the differential diagnosis included infectious diseases, malignancies, and systemic autoimmune or inflammatory diseases. We present an unusual case of a young male with B cell lymphoma who presented with symptoms mimicking systemic vasculitis and review the existing literature.

  13. Diffuse Large B Cell Lymphoma Mimicking Granulomatosis with Polyangiitis

    Science.gov (United States)

    Horowitz, Netanel; Ben-Itzhak, Ofer; Braun-Moscovici, Yolanda

    2016-01-01

    In a patient with systemic multiorgan disease with overlapping features, the differential diagnosis included infectious diseases, malignancies, and systemic autoimmune or inflammatory diseases. We present an unusual case of a young male with B cell lymphoma who presented with symptoms mimicking systemic vasculitis and review the existing literature. PMID:27293945

  14. Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma.

    Science.gov (United States)

    Cardenas, Mariano G; Yu, Wenbo; Beguelin, Wendy; Teater, Matthew R; Geng, Huimin; Goldstein, Rebecca L; Oswald, Erin; Hatzi, Katerina; Yang, Shao-Ning; Cohen, Joanna; Shaknovich, Rita; Vanommeslaeghe, Kenno; Cheng, Huimin; Liang, Dongdong; Cho, Hyo Je; Abbott, Joshua; Tam, Wayne; Du, Wei; Leonard, John P; Elemento, Olivier; Cerchietti, Leandro; Cierpicki, Tomasz; Xue, Fengtian; MacKerell, Alexander D; Melnick, Ari M

    2016-09-01

    Diffuse large B cell lymphomas (DLBCLs) arise from proliferating B cells transiting different stages of the germinal center reaction. In activated B cell DLBCLs (ABC-DLBCLs), a class of DLBCLs that respond poorly to current therapies, chromosomal translocations and amplification lead to constitutive expression of the B cell lymphoma 6 (BCL6) oncogene. The role of BCL6 in maintaining these lymphomas has not been investigated. Here, we designed small-molecule inhibitors that display higher affinity for BCL6 than its endogenous corepressor ligands to evaluate their therapeutic efficacy for targeting ABC-DLBCL. We used an in silico drug design functional-group mapping approach called SILCS to create a specific BCL6 inhibitor called FX1 that has 10-fold greater potency than endogenous corepressors and binds an essential region of the BCL6 lateral groove. FX1 disrupted formation of the BCL6 repression complex, reactivated BCL6 target genes, and mimicked the phenotype of mice engineered to express BCL6 with corepressor binding site mutations. Low doses of FX1 induced regression of established tumors in mice bearing DLBCL xenografts. Furthermore, FX1 suppressed ABC-DLBCL cells in vitro and in vivo, as well as primary human ABC-DLBCL specimens ex vivo. These findings indicate that ABC-DLBCL is a BCL6-dependent disease that can be targeted by rationally designed inhibitors that exceed the binding affinity of natural BCL6 ligands.

  15. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Burkitt's lymphoma: A case report and review

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    Tabita Joy Chettiankandy

    2016-01-01

    Full Text Available B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL and classical Burkitt's lymphoma (BL, is a diagnostic provisional category in the World Health Organization 2008 classification of lymphomas. This category was designed as a measure to accommodate borderline cases that cannot be reliably classified into a single distinct disease entity after all available morphological, immunophenotypical and molecular studies have been performed. Typically, these cases share features intermediate between DLBCL and classical BL or include characteristics of both lymphomas. The rarity of such cases poses a tremendous challenge to both pathologists and oncologists because its differential diagnosis has direct implications for management strategies. In this article, we present a “classical unclassifiable lymphoma with features intermediate between DLBCL and BL” in a young male patient and review of literature.

  16. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Shah, S.; Schrader, K.A.; Waanders, E.; Timms, A.E.; Vijai, J.; Miething, C.; Wechsler, J.; Yang, J.; Hayes, J.; Klein, R.J.; Zhang, Jinghui; Wei, L.; Wu, G.; Rusch, M.; Nagahawatte, P.; Ma, J; Chen, S.C.; Song, G.; Cheng, J.; Meyers, P.; Bhojwani, D.; Jhanwar, S.; Maslak, P.; Fleisher, M.; Littman, J.; Offit, L.; Rau-Murthy, R.; Fleischut, M.H.; Corines, M.; Murali, R.; Gao, X.; Manschreck, C.; Kitzing, T.; Murty, V.V.; Raimondi, S.C.; Kuiper, R.P.; Simons, A.; Schiffman, J.D.; Onel, K.; Plon, S.E.; Wheeler, D.A.; Ritter, D.; Ziegler, D.S.; Tucker, K.; Sutton, R.; Chenevix-Trench, G.; Li, J.; Huntsman, D.G.; Hansford, S.; Senz, J.; Walsh, T.; Lee, M. van der; Hahn, C.N.; Roberts, K.G.; King, M.C.; Lo, S.M.; Levine, R.L.; Viale, A.; Socci, N.D.; Nathanson, K.L.; Scott, H.S.; Daly, M.; Lipkin, S.M.; Lowe, S.W.; Downing, J.R.; Altshuler, D.; Sandlund, J.T.; Horwitz, M.S.; Mullighan, C.G.; Offit, K.

    2013-01-01

    Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL), but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly1

  17. TP53 dysfunction in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Lu, Ting-Xun; Young, Ken H; Xu, Wei; Li, Jian-Yong

    2016-01-01

    The aberrations of TP53 gene and dysregulation of the TP53 pathway are important in the pathogenesis of many human cancers, including malignant lymphomas, especially for diffuse large B cell lymphoma (DLBCL). By regulating many downstream target genes or molecules, TP53 governs major defenses against tumor growth and promotes cellular DNA repair, apoptosis, autophagy, cell cycle arrest, signaling, transcription, immune or inflammatory responses and metabolism. Dysfunction of TP53, including microRNA regulations, copy number alterations of TP53 pathway and TP53 itself, dysregulation of TP53 regulators, and somatic mutations by abnormal TP53 function modes, play an important role in lymphoma generation, progression and invasion. The role of TP53 in DLBCL has been widely explored recently. In this review, we summarized recent advances on different mechanisms of TP53 in DLBCL and new therapeutic approaches to overcome TP53 inactivation.

  18. Prognostic Significance of B-cell Differentiation Genes Encoding Proteins in Diffuse Large B-cell Lymphoma and Follicular Lymphoma Grade 3

    Science.gov (United States)

    Borovečki, Ana; Korać, Petra; Nola, Marin; Ivanković, Davor; Jakšić, Branimir; Dominis, Mara

    2008-01-01

    Aim To define prognostic significance of B-cell differentiation genes encoding proteins and BCL2 and BCL6 gene abnormalities in diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern. Methods In 53 patients with diffuse large B-cell lymphoma and 20 patients with follicular lymphoma grade 3 with >75% follicular growth pattern the following was performed: 1) determination of protein expression of BCL6, CD10, MUM1/IRF4, CD138, and BCL2 by immunohistochemistry; 2) subclassification into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) groups according to the results of protein expression; 3) detection of t(14;18)(q32;q21)/IgH-BCL2 and BCL6 abnormalities by fluorescent in situ hybridization in diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern as well as in GCB and ABC groups; and 4) assessment of the influence of the analyzed characteristics and clinical prognostic factors on overall survival. Results Isolated BCL6 expression was more frequently found in follicular lymphoma grade 3 with >75% follicular growth pattern than in diffuse large B-cell lymphoma (P = 0.030). There were no differences in BCL2 and BCL6 gene abnormalities between diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern. Diffuse large B-cell lymphoma and follicular lymphoma grade 3 with >75% follicular growth pattern patients were equally distributed in GCB and ABC groups. t(14;18)(q32;q21) was more frequently recorded in GCB group, and t(14;18)(q32;q21) with BCL2 additional signals or only BCL2 and IgH additional signals in ABC group (P = 0.004). The GCB and ABC groups showed no difference in BCL6 gene abnormalities. There was no overall survival difference between the patients with diffuse large B-cell lymphoma or follicular lymphoma grade 3 with >75% follicular growth pattern, however, GCB group had longer overall survival than ABC group (P

  19. Primary T-cell lymphoblastic lymphoma in the middle ear.

    Science.gov (United States)

    Li, Bo; Liu, Shixi; Yang, Hui; Wang, Weiya

    2016-03-01

    T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma characterized by precursor T-cell malignancy and lymphadenopathy or mediastinal involvement. We present the case of an 11-year-old boy with a diagnosis of middle ear T-LBL, which manifested as a headache, hearing loss and peripheral facial paralysis. The child was given intensive chemotherapy and had a complete response. To our knowledge, this is the first case reported in the literature of T-LBL originating in the middle ear. This case aims to help clinicians to be vigilant about the possibility of primary lesions at atypical sites in some special diseases.

  20. Lenalidomide in Diffuse Large B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Annalisa Chiappella

    2012-01-01

    Full Text Available Diffuse Large B-cell Lymphomas (DLBCL are the most frequent Non-Hodgkin Lymphomas (NHL. The addition of Rituximab to the standard chemotherapy CHOP improved the outcome in this patients, but so far 40% of patients experienced relapse or progressive disease. Lenalidomide, an immunomodulatory agent, had direct tumoricidal and antiangiogenetic actions on tumor cells and was able to modulate tumor-cell microenvironment, with the restoration of impaired T-cell activity and the formation of immuno-synapsis. Based on these actions, lenalidomide represented an active drug on aggressive relapsed NHL. In this review, the most relevant clinical trials for the use of lenalidomide in DLBCL were reported. Monotherapy with lenalidomide showed an activity in term of overall response rate, with acceptable hematological and extrahematological toxicities in relapsed/refractory aggressive NHL. The role of lenalidomide as salvage therapy in both cell of origin patterns in DLBCL (germinal center B-cell/activated B-cell was reported in preliminary data. Preliminary data regarding the role of lenalidomide in addition to chemoimmunotherapy (R-CHOP in first line clinical trials were discussed; data of safety, feasibility and efficacy were promising.

  1. A B-cell lymphoma case that is unclassifiable, and intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma of lacrimal gland

    Science.gov (United States)

    Yunoki, Tatsuya; Murakami, Jun; Imagawa, Yukihiro; Nakajima, Takahiko; Hayashi, Atsushi

    2017-01-01

    A 60-year-old woman presented with acute eyelid swelling and a subcutaneous hemorrhage in the right eye. Magnetic resonance imaging showed a spherical tumor of the lacrimal gland. The tumor was removed by the Kroenlein method. We diagnosed as a B-cell lymphoma that is unclassifiable, and intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) (intermediate DLBCL/BL) based on its immunohistopathological examination and c-MYC/IgH rearrangement. We administered six cycles of dose-adjusted-EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin hydrochloride, and rituximab) therapy, and remission of the lymphoma was obtained. This is the first case of an intermediate DLBCL/BL of a lacrimal gland. PMID:28203109

  2. Lenalidomide in Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Catherine Thieblemont

    2012-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is the most common form of non-Hodgkin's lymphoma (NHL in adults. Even if the natural history of DLBCL has been improved with the advent of immunochemotherapy, the survival results obtained with current treatment options clearly indicate that new agents or novel approaches are needed. Lenalidomide (Revlimid, Celgene Corporation, Summit, NJ, USA, an analogue of thalidomide, is an immunomodulatory drug with pleiotropic mechanisms of action potentially adding to immunochemotherapy. We present here the biological rational for the use of lenalidomide in DLBCL in light of recent advances in the pathophysiology of the disease and the therapeutic results of the most recent trials published in literature or reported in meetings in relapsed/refractory situations as well as in first-line treatment.

  3. Lenalidomide in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Thieblemont, Catherine; Delfau-Larue, Marie-Hélène; Coiffier, Bertrand

    2012-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma (NHL) in adults. Even if the natural history of DLBCL has been improved with the advent of immunochemotherapy, the survival results obtained with current treatment options clearly indicate that new agents or novel approaches are needed. Lenalidomide (Revlimid, Celgene Corporation, Summit, NJ, USA), an analogue of thalidomide, is an immunomodulatory drug with pleiotropic mechanisms of action potentially adding to immunochemotherapy. We present here the biological rational for the use of lenalidomide in DLBCL in light of recent advances in the pathophysiology of the disease and the therapeutic results of the most recent trials published in literature or reported in meetings in relapsed/refractory situations as well as in first-line treatment.

  4. [Posterior uveitis caused by highly malignant B cell lymphoma].

    Science.gov (United States)

    Held, R; Eckardt, C; Brix, F; Feller, A C

    1989-01-01

    A diagnostic vitrectomy was performed on three patients with posterior uveitis of unknown origin and whose vitrous body was markedly affected. In all cases, cells of high-grade B-cell lymphoma (earlier referred to as reticulum cell sarcoma) were identified by cytological analysis of the specimen. In addition to the ocular findings, one of the three patients showed clinical and radiological evidence of a tumorous mass in the area of the right thalamus at the time of diagnosis. This was interpreted as a cerebral manifestation of the lymphoma. Initially, the other two patients did not show any cerebral involvement. One of them, however, developed clinical symptoms 9 months after diagnosis, which were radiologically verified as tumor infiltration of the cerebellum and the diencephalon. Under radiation therapy, the ocular findings disappeared within a few weeks.

  5. Cytologic Phenotypes of B-Cell Acute Lymphoblastic Leukemia-

    Directory of Open Access Journals (Sweden)

    Ramyar Asghar

    2009-06-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a malignant disorder of lymphoid precursor cells, which could be classified according to morphological and cytochemical methods as well as immunophenotyping. Twenty patients with ALL, who had been referred to the Children's Medical Center Hospital, during the year 2007, were enrolled in this study in order to evaluate the morphologic and immunophenotypic profile of these patients. Cytologic analysis of blood and bone marrow samples revealed that the frequency of ALL-L1 was 70%, followed by ALL-L2 and ALL-L3. The onset age of the patients with ALL-L1 was significantly lower than the patients with L2/L3. Severe anemia was significantly detected more in L1 group. Flow cytometic study of bone marrow showed that 10 cases had Pre-B1 ALL and 7 cases had Pre-B2 ALL, while three cases had Pro-B ALL. Comparisons of the characteristics and clinical manifestations among these groups did not show any appreciable difference. There were an increase percentage of CD20+ cells and a decrease CD10+ cells in pre-B2 group in comparison with pre-B1 group. Fifteen patients were in standard risk and five were in high risk. Although standard risk patients were more common in the group of pre-B1, this was not significant. Our results confirm the previous reports indicating heterogeneity of ALL. Immunophenotyping is not the only diagnostic test of importance, while morphological assessment still can be used in the diagnosis and classification of the disease.

  6. The Role of c-MYC in B-Cell Lymphomas: Diagnostic and Molecular Aspects.

    Science.gov (United States)

    Nguyen, Lynh; Papenhausen, Peter; Shao, Haipeng

    2017-04-05

    c-MYC is one of the most essential transcriptional factors, regulating a diverse array of cellular functions, including proliferation, growth, and apoptosis. Dysregulation of c-MYC is essential in the pathogenesis of a number of B-cell lymphomas, but is rarely reported in T-cell lymphomas. c-MYC dysregulation induces lymphomagenesis by loss of the tight control of c-MYC expression, leading to overexpression of intact c-MYC protein, in contrast to the somatic mutations or fusion proteins seen in many other oncogenes. Dysregulation of c-MYC in B-cell lymphomas occurs either as a primary event in Burkitt lymphoma, or secondarily in aggressive lymphomas such as diffuse large B-cell lymphoma, plasmablastic lymphoma, mantle cell lymphoma, or double-hit lymphoma. Secondary c-MYC changes include gene translocation and gene amplification, occurring against a background of complex karyotype, and most often confer aggressive clinical behavior, as evidenced in the double-hit lymphomas. In low-grade B-cell lymphomas, acquisition of c-MYC rearrangement usually results in transformation into highly aggressive lymphomas, with some exceptions. In this review, we discuss the role that c-MYC plays in the pathogenesis of B-cell lymphomas, the molecular alterations that lead to c-MYC dysregulation, and their effect on prognosis and diagnosis in specific types of B-cell lymphoma.

  7. B-cell lymphomas with features intermediate between distinct pathologic entities. From pathogenesis to pathology.

    Science.gov (United States)

    Carbone, Antonino; Gloghini, Annunziata; Aiello, Antonella; Testi, Adele; Cabras, Antonello

    2010-05-01

    Published in September 2008, the updated World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues introduces provisional borderline categories for lymphoma cases that demonstrate overlapping clinical, morphological, and/or immunophenotypic features between well-established entities. These overlapping features pose real diagnostic challenges especially in identifying atypical cases of diffuse large B-cell lymphoma, Hodgkin lymphoma, and Burkitt lymphoma. Lymphoma cases showing borderline features between T-cell/histiocyte-rich large B-cell lymphoma and nodular lymphocyte predominant Hodgkin lymphoma are not included within the borderline categories provisionally recognized by the updated classification. Within the borderline categories, there are cases combining features of primary mediastinal large B-cell lymphoma and classical Hodgkin lymphoma. Many of these cases resemble classical Hodgkin lymphoma but have a large number of tumor cells expressing CD20, CD45, and B-cell transcription factors. Alternatively, these cases may resemble primary mediastinal large B-cell lymphoma but contain tumor cells resembling Reed-Sternberg cells and displaying an aberrant phenotype such as CD20(-), CD15(-/+) CD45(+), CD30(+), Pax5(+), OCT2(+/-), and BOB1(+/-). Another new borderline category defining B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, represents a biologically heterogeneous group. Cases with morphologic features intermediate and with CD10/BCL6 coexpression should be placed in diffuse large B-cell lymphoma/Burkitt lymphoma category if tumor cells also show strong BCL2 staining and/or a Ki67 proliferation index of less than 90%. When MYC rearrangements are present in these cases, the lymphomas often have atypical features, including concurrent rearrangements of BCL2 and/or BCL6 genes (so-called double/triple-hit lymphomas) and more aggressive behavior. For the

  8. T-cell leukemia 1 expression in nodal Epstein-Barr virus-negative diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma.

    Science.gov (United States)

    Gualco, Gabriela; Weiss, Lawrence M; Barber, Glen N; Bacchi, Carlos E

    2010-09-01

    The physiologic expression of the product of the proto-oncogene TCL1 (T-cell leukemia 1) is primarily restricted to early embryonic cells. In nonneoplastic B cells, the expression of TCL1 is determined by the differentiation step with silencing at the germinal center stage. TCL1 protein is overexpressed in a wide variety of human diseases. It has been shown that TCL1 is a powerful B-cell oncogene, which has been implicated in the pathogenesis of various types of mature B-cell lymphomas. There is no comparative information in the literature addressing the expression of TCL1 in pediatric and adult nodal diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma. We studied 55 cases of adult and pediatric diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma to analyze the phenotypic profile of these lymphomas, including TCL1 expression, and its relationship with clinical outcome in different age groups. The cases were analyzed by immunohistochemistry for the expression of TCL1, CD10, BCL-2, BCL-6, and MUM1. We also evaluated c-MYC translocation by fluorescence in situ hybridization. TCL1 was observed in 11 cases, 5 pediatric and 6 adult cases, all but one diffuse large B-cell lymphoma. Pediatric cases showed a significant association between TCL1 expression, high proliferative index, and presence of c-MYC translocation. TCL1 positivity was predominantly found in germinal center phenotype diffuse large B-cell lymphoma. Overall survival was worse in adult TCL1-positive cases than pediatric ones. Primary mediastinal large B-cell lymphomas infrequently expressed TCL1 in both age groups.

  9. Clinicopathological features of aggressive B-cell lymphomas including B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell and Burkitt lymphomas: a study of 44 patients from Argentina.

    Science.gov (United States)

    Bürgesser, María Virginia; Gualco, Gabriela; Diller, Ana; Natkunam, Yasodha; Bacchi, Carlos E

    2013-06-01

    Aggressive B-cell lymphomas incorporate a wide spectrum of lymphomas that pose challenges in diagnosis as well as treatment. We evaluated the clinicopathological features of 44 patients with aggressive B-cell lymphomas which were classified into 3 groups based on the World Health Organization 2008 classification as follows: including 30 cases of diffuse large B-cell lymphoma (DLBCL), 8 cases of Burkitt lymphoma (BL) and 6 cases of B-cell lymphoma, unclassifiable, with features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma (BCLU). Male predominance was observed in BL and BCLU groups and the mean age varied from 29 years in BL, 61 years in DLBCL and 70 years in BCLU. Patients with BCLU presented at more advanced stages and had a higher international prognostic index. By immunohistochemistry, they shared characteristics of both BL (including more frequent expression of SOX11) and DLBCL. FISH analyses showed three cases with more than one rearrangement: one MYC/BCL2 and two BCL2/BCL6, in addition to which one case with BCL2/IGH translocation and another with MYC rearrangement were also detected. The mean follow-up survival time of BCLU was 6.6 months, which was significantly shorter in comparison to DLBCL (31 months) and BL (30 months), respectively. The importance of recognizing this BCLU group relies on its different clinical course, poor prognosis and shorter survival than DLBCL and BL. An accurate diagnosis is critical for risk stratification and to improve therapeutic approaches and outcomes.

  10. Primary intravascular large B-cell lymphoma of pituitary

    Directory of Open Access Journals (Sweden)

    K R Anila

    2012-01-01

    Full Text Available A 68-year-old retired nurse, who was a known hypertensive on medication, presented with prolonged fever of 2-month duration without any clinical evidence of infection. On examination she had altered mental status. She also had other nonspecific complaints such as sleep disturbances, loss of weight, etc. On investigation, she was found to have anemia, thrombocytopenia, raised erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, and lactate dehydrogenase (LDH values. She also had electrolyte imbalance. Radiological evaluation of brain showed mass lesion in the sella turcica, suggestive of pituitary adenoma. Biochemical evaluation showed hypopituitarism. Trans-sphenoidal biopsy was done. Based on histopathological and immunohistochemical findings a diagnosis of intravascular large B-cell lymphoma (IVLBCL of pituitary was made. Our patient′s condition deteriorated rapidly and she succumbed to her illness before therapy could be initiated. We are reporting this case because of the rare subtype of large B-cell lymphoma presenting at an extremely unusual primary site.

  11. Anticancer Effect of Curcumin on B Cell non- Hodgkin's Lymphoma

    Institute of Scientific and Technical Information of China (English)

    SUN Chunyan; LIU Xinyue; CHEN Yan; LIU Fang

    2005-01-01

    To explore the anticancer effect of curcumin on human B cell non-Hodgkin's lymphoma and compare its effects on human B cell non-Hodgkin's lymphoma cells and normal peripheral blood mononuclear cells (NPBMNCs). MTT assay was used to study the effect of curcumin on the growth of Raji cells and NPBMNCs. The effect of curcumin on the apoptosis of Raji cells and NPBMNC were studied by flow cytometry and TDT-mediated dUTP nick and labeling (TUNEL). The effect of curcumin on the cell cycle of Raji cells were examined by propidium iodide staining flow cytometry. The results showed that curcumin strongly inhibited ±1.82 μmol/L and curcumin induced Raji cell apoptosis in a time- and dose-dependent manner. Raji cells treated with curcumin showed curcumin did not demonstrate apparent proliferation inhibition and apoptosis induction in NPBMNCs. It was concluded that curcumin is able to inhibit the proliferation of Raji cells by regulating the cell cycle and inducing the cell apoptosis. Morever, curcumin has low toxicity on NPBMNCs but can selectively induce apoptosis in Raji cells.

  12. Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia or B-Cell Prolymphocytic Leukemia

    Science.gov (United States)

    2016-07-29

    Post-transplant Lymphoproliferative Disorder; B-Cell Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Recurrent Lymphoplasmacytic Lymphoma

  13. Precursor B-cell acute lymphoblastic leukemia presenting as obstructive jaundice: a case report

    Directory of Open Access Journals (Sweden)

    Awasum Michael

    2011-07-01

    Full Text Available Abstract Introduction Acute leukemias very rarely present with jaundice. Herein we report a case of precursor B-cell acute lymphoblastic leukemia that presented with jaundice in an adult. Case presentation A 44-year-old Hispanic man presented with right upper quadrant abdominal pain and jaundice. His initial blood work revealed pancytopenia and hyperbilirubinemia. Direct bilirubin was more than 50% of the total. His imaging studies were unremarkable except for hepatomegaly. All blood screening tests for various hepatocellular etiologies were normal. A diagnosis of precursor B-cell acute lymphoblastic leukemia was made upon liver biopsy. It also showed lymphocytic infiltration of the hepatic parenchyma leading to bile stasis. The diagnosis was subsequently confirmed upon bone marrow biopsy. The patient was treated with a hyperfractionated cyclophosphamide/vincristine/doxorubicin/dexamethasone regimen. Conclusion Acute lymphoblastic leukemia should be one of the differential diagnoses that should be considered when initial work-up for jaundice is inconclusive. Some cases of acute lymphoblastic leukemia have been reported in both adults and children to have presented with the initial manifestation of jaundice, but only a few had no radiographic evidence of biliary obstruction. Such presentation can pose a serious diagnostic dilemma for clinicians. This manuscript attempts to highlight it. Moreover, we believe that if acute lymphoblastic leukemia presentations similar to this case continue to be reported in adults or children, a specific immunophenotypic expression and cytogenetic abnormality may be found to be associated with hepatic infiltration by leukemia. This may substantially contribute to the further understanding of the pathophysiology of this hematologic disease.

  14. Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)

    Science.gov (United States)

    2017-01-24

    B-Cell Chronic Lymphocytic Leukemia; Monoclonal B-Cell Lymphocytosis; Lymhoma, Small Lymphocytic; Chronic Lymphocytic Leukemia; Lymphoplasmacytic Lymphoma; Waldenstrom Macroglobulinemia; Splenic Marginal Zone Lymphoma

  15. Lenalidomide and Combination Chemotherapy (DA-EPOCH-R) in Treating Patients With MYC-Associated B-Cell Lymphomas

    Science.gov (United States)

    2016-08-24

    Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Chronic Lymphocytic

  16. Detection and outcome of occult leptomeningeal disease in diffuse large B-cell lymphoma and Burkitt lymphoma

    NARCIS (Netherlands)

    W.H. Wilson (Wyndham); J.E.C. Bromberg (Jacolien); M. Stetler-Stevenson (Maryalice); S.M. Steinberg (Seth); L. Martin-Martin (Lourdes); C. Muñiz (Carmen); J.M. Sancho (Juan Manuel); L. Caballero; M.A. Davidis (Marjan); R.A. Brooimans (Rik); B. Sanchez-Gonzalez (Blanca); A. Salar (Antonio); E. González-Barca (Eva); J.M. Ribera (Josep Maria); M. Shovlin (Margaret); A. Filie (Armando); K. Dunleavy (Kieron); T. Mehrling (Thomas); M. Spina (Michele); A. Orfao (Alberto)

    2014-01-01

    textabstractThe benefit of intrathecal therapy and systemic rituximab on the outcome of diffuse large B-cell lymphoma at risk of central nervous system disease is controversial. Furthermore, the effect of intrathecal treatment and rituximab in diffuse large B-cell and Burkitt lymphoma with occult le

  17. Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases

    DEFF Research Database (Denmark)

    Miletic, Ana V; Anzelon-Mills, Amy N; Mills, David M

    2010-01-01

    results in lethal T cell lymphomas, we find that animals lacking PTEN or SHIP in B cells show no evidence of malignancy. However, concomitant deletion of PTEN and SHIP (bPTEN/SHIP(-/-)) results in spontaneous and lethal mature B cell neoplasms consistent with marginal zone lymphoma or, less frequently......, follicular or centroblastic lymphoma. bPTEN/SHIP(-/-) B cells exhibit enhanced survival and express more MCL1 and less Bim. These cells also express low amounts of p27(kip1) and high amounts of cyclin D3 and thus appear poised to undergo proliferative expansion. Unlike normal B cells, bPTEN/SHIP(-/-) B cells...... proliferate to the prosurvival factor B cell activating factor (BAFF). Interestingly, although BAFF availability may promote lymphoma progression, we demonstrate that BAFF is not required for the expansion of transferred bPTEN/SHIP(-/-) B cells. This study reveals that PTEN and SHIP act cooperatively...

  18. Heart of Lymphoma: Primary Mediastinal Large B-Cell Lymphoma with Endomyocardial Involvement

    Directory of Open Access Journals (Sweden)

    Elisa Rogowitz

    2013-01-01

    Full Text Available Primary mediastinal B-cell lymphoma (PMBCL is an uncommon aggressive subset of diffuse large B-cell lymphomas. Although PMBCL frequently spreads locally from the thymus into the pleura or pericardium, it rarely invades directly through the heart. Herein, we report a case of a young Mexican female diagnosed with PMBCL with clear infiltration of lymphoma through the cardiac wall and into the right atrium and tricuspid valve leading to tricuspid regurgitation. This was demonstrated by cardiac MRI and transthoracic echocardiogram. In addition, cardiac MRI and CT scan of the chest revealed the large mediastinal mass completely surrounding and eroding into the superior vena cava (SVC wall causing a collar of stokes. The cardiac and SVC infiltration created a significant therapeutic challenge as lymphomas are very responsive to chemotherapy, and treatment could potentially lead to vascular wall rupture and hemorrhage. Despite the lack of conclusive data on chemotherapy-induced hemodynamic compromise in such scenarios, her progressive severe SVC syndrome and respiratory distress necessitated urgent intervention. In addition to the unique presentation of this rare lymphoma, our case report highlights the safety of R-CHOP treatment.

  19. Multifocal Extranodal Involvement of Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Devrim Cabuk

    2013-01-01

    Full Text Available Endobronchial involvement of extrapulmonary malignant tumors is uncommon and mostly associated with breast, kidney, colon, and rectum carcinomas. A 68-year-old male with a prior diagnosis of colon non-Hodgkin lymphoma (NHL was admitted to the hospital with a complaint of cough, sputum, and dyspnea. The chest radiograph showed right hilar enlargement and opacity at the right middle zone suggestive of a mass lesion. Computed tomography of thorax revealed a right-sided mass lesion extending to thoracic wall with the destruction of the third and the fourth ribs and a right hilar mass lesion. Fiberoptic bronchoscopy was performed in order to evaluate endobronchial involvement and showed stenosis with mucosal tumor infiltration in right upper lobe bronchus. The pathological examination of bronchoscopic biopsy specimen reported diffuse large B-cell lymphoma and the patient was accepted as the endobronchial recurrence of sigmoid colon NHL. The patient is still under treatment of R-ICE (rituximab-ifosfamide-carboplatin-etoposide chemotherapy and partial regression of pulmonary lesions was noted after 3 courses of treatment.

  20. Primary Mediastinal Large B-Cell Lymphoma during Pregnancy

    Directory of Open Access Journals (Sweden)

    Cesar A. Perez

    2012-01-01

    Full Text Available Non-Hodgkin’s Lymphoma (NHL rarely presents during pregnancy and primary mediastinal large B-cell lymphoma (PMLBCL accounts for approximately 2.5% of patients with NHL. The case of a 22-year-old woman who was diagnosed with Stage IIA PMLBCL during week 13 of her intrauterine pregnancy is described. The staging consisted in computed tomography (CT of the chest and magnetic resonance imaging (MRI of the abdomen and pelvis. She was managed with R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone for a total of six cycles and, because of the early presentation during the second trimester, she received the entire chemotherapy course during the pregnancy. She delivered a healthy baby at 34 weeks of pregnancy and a 18FDG-PET/CT scan demonstrated complete remission after delivery. After 20 months of follow up she remains with no evidence of disease and her 1-year-old son has shown no developmental delays or physical abnormalities. PMLBCL, although an uncommon subgroup of DLBCL, may present during pregnancy and R-CHOP should be considered as one suitable option in this complex scenario.

  1. Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults

    Directory of Open Access Journals (Sweden)

    Lee KJ

    2016-08-01

    Full Text Available Kum Ja Lee,1 Vivian Chow,1 Ashley Weissman,2 Sunil Tulpule,3 Ibrahim Aldoss,4 Mojtaba Akhtari5 1Department of Clinical Pharmacy and Pharmaceutical Economics and Policy, University of Southern California, 2Department of Pharmacy, University of Southern California Norris Cancer Hospital, Los Angeles, CA, 3Department of Medicine, Raritan Bay Medical Center, Perth Amboy, NJ, 4Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, 5Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA Abstract: Adults with relapsed or refractory B-cell acute lymphoblastic leukemia have a dismal prognosis with a short median overall survival that can be measured in months. Because most patients will have chemotherapy-resistant disease, allogeneic hematopoietic stem cell transplantation remains the only potentially curative treatment. Despite advances in current management, patients continue to have poor outcomes and lack of durable responses. Thus, new therapies with alternative modes of actions are currently being investigated. Blinatumomab is a novel bispecific T-cell engager that simultaneously binds CD3-positive cytotoxic T-cells and CD19-positive B-cells, resulting in selective lysis of tumor cells. It has shown promising results in patients with relapsed or refractory acute lymphoblastic leukemia or those achieving hematologic response with persistent minimum residual disease. Future clinical trials will answer questions regarding its optimal place in the treatment paradigm. Dose-limiting toxicities include immunological toxicities and cytokine release syndrome. However, most patients tolerate the therapy relatively well. This review will focus on the pharmacology, clinical efficacy, and safety of blinatumomab in the treatment of adult B-cell acute lymphoblastic leukemia while highlighting its unique drug

  2. Tumefactive intracranial presentation of precursor B-cell acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Forester, Craig M. [University of Utah, Salt Lake City, UT (United States); Braunreiter, Chi L. [University of Utah, Division of Pediatric Hematology Oncology, Primary Children' s Medical Center, Salt Lake City, UT (United States); Helen DeVos Children' s Hospital, Department of Pediatric Hematology Oncology, Grand Rapids, MI (United States); Yaish, Hasan; Afify, Zeinab [University of Utah, Division of Pediatric Hematology Oncology, Primary Children' s Medical Center, Salt Lake City, UT (United States); Hedlund, Gary L. [Primary Children' s Medical Center, Department of Pediatric Radiology, Salt Lake City, UT (United States)

    2009-11-15

    In children, leukemia is the most common malignancy, and approximately 75% of leukemias are acute lymphoblastic leukemia (ALL). Central nervous system leukemia is found at diagnosis in fewer than 5% of children with ALL. Leukemic intracranial masses have been described with acute myeloid leukemia, but ALL presenting as a mass lesion is rare. We describe a unique case of an intracranial confirmed precursor B cell (pre-B) ALL mass in a 13-year-old girl that was diagnosed by brain CT, MRI and cerebral angiography, and confirmed by biopsy. This report details pertinent history and distinguishing imaging features of an intracranial ALL tumefaction. (orig.)

  3. Essential role of MALT1 protease activity in activated B cell-like diffuse large B-cell lymphoma

    OpenAIRE

    Hailfinger, Stephan; Lenz, Georg; Ngo, Vu; Posvitz-Fejfar, Anita; Rebeaud, Fabien; Guzzardi, Montserrat; Penas, Eva-Maria Murga; Dierlamm, Judith; Chan, Wing C.; Staudt, Louis M.; Thome, Margot

    2009-01-01

    A key element for the development of suitable anti-cancer drugs is the identification of cancer-specific enzymatic activities that can be therapeutically targeted. Mucosa-associated lymphoid tissue transformation protein 1 (MALT1) is a proto-oncogene that contributes to tumorigenesis in diffuse large B-cell lymphoma (DLBCL) of the activated B-cell (ABC) subtype, the least curable subtype of DLBCL. Recent data suggest that MALT1 has proteolytic activity, but it is unknown whether this activity...

  4. Immunohistochemical classification and prognosis of diffuse large B-cell lymphoma in China

    Institute of Scientific and Technical Information of China (English)

    陈燕

    2014-01-01

    Objective To study the immunohistochemical classification and prognosis of diffuse large B-cell lymphoma(DLBCL).Methods A total of 148 cases of DLBCL were classified into germinal center B-cell-like(GCB)and non-GCB/activated B-cell-like(ABC)subtypes by Hans,Choi and Tally immunohistochemical stain algorithms.The clinical features and survival data of GCB

  5. Ran GTPase-activating protein 1 is a therapeutic target in diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Kung-Chao Chang

    Full Text Available Lymphoma-specific biomarkers contribute to therapeutic strategies and the study of tumorigenesis. Diffuse large B-cell lymphoma (DLBCL is the most common type of malignant lymphoma. However, only 50% of patients experience long-term survival after current treatment; therefore, developing novel therapeutic strategies is warranted. Comparative proteomic analysis of two DLBCL lines with a B-lymphoblastoid cell line (LCL showed differential expression of Ran GTPase-activating protein 1 (RanGAP1 between them, which was confirmed using immunoblotting. Immunostaining showed that the majority of DLBCLs (92%, 46/50 were RanGAP1(+, while reactive lymphoid hyperplasia (n = 12 was RanGAP1(+ predominantly in germinal centers. RanGAP1 was also highly expressed in other B-cell lymphomas (BCL, n = 180 with brisk mitotic activity (B-lymphoblastic lymphoma/leukemia: 93%, and Burkitt lymphoma: 95% or cell-cycle dysregulation (mantle cell lymphoma: 83%, and Hodgkin's lymphoma 91%. Interestingly, serum RanGAP1 level was higher in patients with high-grade BCL (1.71 ± 2.28 ng/mL, n = 62 than in low-grade BCL (0.75 ± 2.12 ng/mL, n = 52 and healthy controls (0.55 ± 1.58 ng/mL, n = 75 (high-grade BCL vs. low-grade BCL, p = 0.002; high-grade BCL vs. control, p < 0.001, Mann-Whitney U test. In vitro, RNA interference of RanGAP1 showed no effect on LCL but enhanced DLBCL cell death (41% vs. 60%; p = 0.035 and cell-cycle arrest (G0/G1: 39% vs. 49%, G2/M: 19.0% vs. 7.5%; p = 0.030 along with decreased expression of TPX2 and Aurora kinases, the central regulators of mitotic cell division. Furthermore, ON 01910.Na (Estybon, a multikinase inhibitor induced cell death, mitotic cell arrest, and hyperphosphorylation of RanGAP1 in DLBCL cell lines but no effects in normal B and T cells. Therefore, RanGAP1 is a promising marker and therapeutic target for aggressive B-cell lymphoma, especially DLBCL.

  6. Identification of highly methylated genes across various types of B-cell non-hodgkin lymphoma.

    Directory of Open Access Journals (Sweden)

    Nicole Bethge

    Full Text Available Epigenetic alterations of gene expression are important in the development of cancer. In this study, we identified genes which are epigenetically altered in major lymphoma types. We used DNA microarray technology to assess changes in gene expression after treatment of 11 lymphoma cell lines with epigenetic drugs. We identified 233 genes with upregulated expression in treated cell lines and with downregulated expression in B-cell lymphoma patient samples (n = 480 when compared to normal B cells (n = 5. The top 30 genes were further analyzed by methylation specific PCR (MSP in 18 lymphoma cell lines. Seven of the genes were methylated in more than 70% of the cell lines and were further subjected to quantitative MSP in 37 B-cell lymphoma patient samples (diffuse large B-cell lymphoma (activated B-cell like and germinal center B-cell like subtypes, follicular lymphoma and Burkitt`s lymphoma and normal B lymphocytes from 10 healthy donors. The promoters of DSP, FZD8, KCNH2, and PPP1R14A were methylated in 28%, 67%, 22%, and 78% of the 36 tumor samples, respectively, but not in control samples. Validation using a second series of healthy donor controls (n = 42; normal B cells, peripheral blood mononuclear cells, bone marrow, tonsils and follicular hyperplasia and fresh-frozen lymphoma biopsies (n = 25, confirmed the results. The DNA methylation biomarker panel consisting of DSP, FZD8, KCNH2, and PPP1R14A was positive in 89% (54/61 of all lymphomas. Receiver operating characteristic analysis to determine the discriminative power between lymphoma and healthy control samples showed a c-statistic of 0.96, indicating a possible role for the biomarker panel in monitoring of lymphoma patients.

  7. Study of Safety,Efficacy and Pharmacokinetics of CT-1530 in Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia

    Science.gov (United States)

    2016-12-01

    Relapsed or Refractory B Cell Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Waldenstrom's Macroglobulinemia; Mantle Zone Lymphoma Refractory/Recurrent; Follicle Centre Lymphoma Diffuse; Diffuse Large B Cell Lymphoma

  8. Diagnosis and immunophenotype of 188 pediatric lymphoblastic lymphomas treated within a randomized prospective trial: experiences and preliminary recommendations from the European childhood lymphoma pathology panel.

    NARCIS (Netherlands)

    Oschlies, I.; Burkhardt, B.; Chassagne-Clement, C.; d'Amore, E.S.; Hansson, U.; Hebeda, K.M.; McCarthy, K.; Kodet, R.; Maldyk, J.; Mullauer, L.; Porwit, A.; Schmatz, A.I.; Tinguely, M.; Abramov, D.; Wotherspoon, A.; Zimmermann, M.; Reiter, A.; Klapper, W.

    2011-01-01

    The majority of lymphoblastic (precursor cell) neoplasms presents as leukemias. Consequently, the guidelines for lineage determination and subtyping of precursor cell neoplasms were primarily established for flow cytometry methods. Large-scale studies of nonleukemic lymphoblastic lymphomas are lacki

  9. Deletion of genes encoding PU.1 and Spi-B in B cells impairs differentiation and induces pre-B cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Sokalski, Kristen M; Li, Stephen K H; Welch, Ian; Cadieux-Pitre, Heather-Anne T; Gruca, Marek R; DeKoter, Rodney P

    2011-09-01

    The E26 transformation-specific (Ets) transcription factor PU.1 is required to generate lymphoid progenitor cells from hematopoietic stem cells, but it is not required to generate B cells from committed B-cell lineage progenitors. We hypothesized that PU.1 function in B-cell differentiation is complemented by the related Ets transcription factor Spi-B. To test this hypothesis, mice were generated lacking both PU.1 and Spi-B in the B-cell lineage. Unlike mice lacking PU.1 or Spi-B, mice deficient in both PU.1 and Spi-B in the B-cell lineage had reduced frequencies of B cells as well as impaired B-cell differentiation. Strikingly, all PU.1 and Spi-B-deficient mice developed pre-B cell acute lymphoblastic leukemia before 30 weeks of age. Pre-B cells accumulated in the thymus resulting in massive thymic enlargement and dyspnea. These findings demonstrate that PU.1 and Spi-B are essential transcriptional regulators of B-cell differentiation as well as novel tumor suppressors in the B-cell lineage.

  10. Primary cutaneous diffuse large B-cell lymphoma of the upper limb: A fascinating entity

    Directory of Open Access Journals (Sweden)

    Manoj Madakshira Gopal

    2013-01-01

    Full Text Available Primary cutaneous lymphomas are defined as lymphoid neoplasms that present themselves clinically on the skin and do not have extra-cutaneous disease, when the diagnosis is made or even after 6 months of the diagnosis. Primary cutaneous lymphomas of B-cells are less frequent than lymphomas of T-cells. Primary B-cell lymphomas have a better prognosis than secondary B-cell lymphomas. Primary B-cell cutaneous lymphomas are classified into five types according to the World Health Organization and European Organization for Research and Treatment of Cancer classification. The primary diffuse large B-cell cutaneous lymphoma - leg type corresponds to approximately 5-10% of the B-cell cutaneous lymphomas. It is predominantly seen in elderly people and has a female preponderance. Skin lesions can be single, multiple, and even grouped. A 5-year survival rate ranges from 36 to 100% of the cases. The expression of Bcl-2, presence of multiple lesions, and involvement of both the upper limbs lead to a worse prognosis. Very few cases have been described in the literature.

  11. Farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature B cell lymphomas

    Directory of Open Access Journals (Sweden)

    Refaeli Yosef

    2008-05-01

    Full Text Available Abstract Background We have used a mouse model based on overexpression of c-Myc in B cells genetically engineered to be self-reactive to test the hypothesis that farnesyl transferase inhibitors (FTIs can effectively treat mature B cell lymphomas. FTIs are undergoing clinical trials to treat both lymphoid and non-lymphoid malignancies and we wished to obtain evidence to support the inclusion of B cell lymphomas in future trials. Results We report that two FTIs, L-744,832 and SCH66336, blocked the growth of mature B cell lymphoma cells in vitro and in vivo. The FTI treatment affected the proliferation and survival of the transformed B cells to a greater extent than naïve B cells stimulated with antigen. In syngeneic mice transplanted with the transgenic lymphoma cells, L-744,832 treatment prevented the growth of the tumor cells and the morbidity associated with the resulting lymphoma progression. Tumors that arose from transplantation of the lymphoma cells regressed with as little as three days of treatment with L-744,832 or SCH66336. Treatment of these established lymphomas with L-744,832 for seven days led to long-term remission of the disease in approximately 25% of animals. Conclusion FTI treatment can block the proliferation and survival of self-reactive transformed B cells that overexpress Myc. In mice transplanted with mature B cell lymphomas, we found that FTI treatment led to regression of disease. FTIs warrant further consideration as therapeutic agents for mature B cell lymphomas and other lymphoid tumors.

  12. An Unusual Presentation of B-Cell Lymphoma as a Large Isolated Epiglottic Mass: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Changxing Liu

    2016-01-01

    Full Text Available Extranodal presentation of B-cell lymphoma is uncommon. Isolated primary epiglottic B-cell lymphoma is even rarer. To our knowledge, there has been only one description of isolated B-cell lymphoma presenting as a large epiglottic mass. We report an unusual type of B-cell lymphoma of the epiglottis, as it could not be subtyped based on routine staining and hybridization. The lymphoma presented as a large isolated globular mass pedicled to the epiglottis, occupying most of the oropharynx, but did not have any ball-valving effect or increased respiratory efforts. Initial radiographic findings were nonspecific. The diagnosis of B-cell lymphoma was determined by transoral incisional biopsy under local anesthesia. The condition was treated successfully with chemoradiation. The current standard of treatment for high grade B-cell lymphoma is concurrent chemoradiotherapy, with excellent prognosis. Although rare, B-cell lymphoma should be considered when investigating pedunculated hypopharyngeal masses.

  13. Cerebral infratentorial large B-cell lymphoma presenting as Parkinsonism.

    Science.gov (United States)

    Lin, Chih-Ming; Hong, Kelvin

    2010-03-01

    Though rare, primary intracranial tumors can present with Parkinsonian symptoms, and diagnosis can be delayed unless there is a high index of suspicion. We herein present an 81-year-old man who was seen in our neurology clinic due to acute onset of unsteady gait and altered consciousness. Parkinsonism was initially diagnosed because of the typical manifestations. Levodopa was prescribed; however, there was a limited effect on his symptoms. Upon detail history and neurological examination, left sided hemiparesis was disclosed. Cerebral imaging studies revealed a solid mass over the right infratentorial para-midbrain area leading to reactive obstructive hydrocephalus. Work-up including chest and abdominal CT scanning, upper and lower GI endoscopy, and tumor marker studies failed to uncover any abnormalities. A neurosurgeon was consulted and a shunt procedure and biopsy of the infratentorial mass were performed. Histopathological examination of the biopsy tissue revealed tumor diffusely intermixed with large cells consistent with large B-cell lymphoma. The patient and his family declined further treatment. Though rare, cerebral tumors can present with Parkinsonian features and represent a diagnostic challenge. Clinicians should be aware of the possibility of cerebral neoplasms causing Parkinsonism, and include them in the differential diagnosis, especially for patients presenting with atypical Parkinsonian features, or those not responsive to initial therapy.

  14. Epigenomic evolution in diffuse large B-cell lymphomas.

    Science.gov (United States)

    Pan, Heng; Jiang, Yanwen; Boi, Michela; Tabbò, Fabrizio; Redmond, David; Nie, Kui; Ladetto, Marco; Chiappella, Annalisa; Cerchietti, Leandro; Shaknovich, Rita; Melnick, Ari M; Inghirami, Giorgio G; Tam, Wayne; Elemento, Olivier

    2015-04-20

    The contribution of epigenomic alterations to tumour progression and relapse is not well characterized. Here we characterize an association between disease progression and DNA methylation in diffuse large B-cell lymphoma (DLBCL). By profiling genome-wide DNA methylation at single-base pair resolution in thirteen DLBCL diagnosis-relapse sample pairs, we show that DLBCL patients exhibit heterogeneous evolution of tumour methylomes during relapse. We identify differentially methylated regulatory elements and determine a relapse-associated methylation signature converging on key pathways such as transforming growth factor-β (TGF-β) receptor activity. We also observe decreased intra-tumour methylation heterogeneity from diagnosis to relapsed tumour samples. Relapse-free patients display lower intra-tumour methylation heterogeneity at diagnosis compared with relapsed patients in an independent validation cohort. Furthermore, intra-tumour methylation heterogeneity is predictive of time to relapse. Therefore, we propose that epigenomic heterogeneity may support or drive the relapse phenotype and can be used to predict DLBCL relapse.

  15. The B cell antigen receptor and overexpression of MYC can cooperate in the genesis of B cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Yosef Refaeli

    2008-06-01

    Full Text Available A variety of circumstantial evidence from humans has implicated the B cell antigen receptor (BCR in the genesis of B cell lymphomas. We generated mouse models designed to test this possibility directly, and we found that both the constitutive and antigen-stimulated state of a clonal BCR affected the rate and outcome of lymphomagenesis initiated by the proto-oncogene MYC. The tumors that arose in the presence of constitutive BCR differed from those initiated by MYC alone and resembled chronic B cell lymphocytic leukemia/lymphoma (B-CLL, whereas those that arose in response to antigen stimulation resembled large B-cell lymphomas, particularly Burkitt lymphoma (BL. We linked the genesis of the BL-like tumors to antigen stimulus in three ways. First, in reconstruction experiments, stimulation of B cells by an autoantigen in the presence of overexpressed MYC gave rise to BL-like tumors that were, in turn, dependent on both MYC and the antigen for survival and proliferation. Second, genetic disruption of the pathway that mediates signaling from the BCR promptly killed cells of the BL-like tumors as well as the tumors resembling B-CLL. And third, growth of the murine BL could be inhibited by any of three distinctive immunosuppressants, in accord with the dependence of the tumors on antigen-induced signaling. Together, our results provide direct evidence that antigenic stimulation can participate in lymphomagenesis, point to a potential role for the constitutive BCR as well, and sustain the view that the constitutive BCR gives rise to signals different from those elicited by antigen. The mouse models described here should be useful in exploring further the pathogenesis of lymphomas, and in preclinical testing of new therapeutics.

  16. Intravascular large B-cell lymphoma presenting with fulminant pseudomembranous colitis.

    Science.gov (United States)

    Wang, Tao; Ghaffar, Hasan; Grin, Andrea

    2013-05-01

    Intravascular large B-cell lymphoma is a rare entity that usually presents in late stages with non-specific symptoms. We present a case of an incidentally discovered intravascular large B-cell lymphoma in a 78-year-old man who underwent colectomy for medically refractory pseudomembranous colitis. The malignant lymphocytes were preferentially localized to small colonic submucosal vasculature, without any evidence of an extravascular tumor mass. The gastrointestinal system is an exceeding rare initial diagnostic site for intravascular lymphoma, and presentation with pseudomembranous colitis has not been previously reported. We discuss the current definition of intravascular lymphoma, clinicopathological variants, differential diagnoses, as well as current therapy.

  17. An Open-Label, Multicenter, Phase 1/2 Study of E7438 (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Advanced Solid Tumors or With B-cell Lymphomas

    Science.gov (United States)

    2016-09-01

    B-cell Lymphomas (Phase 1); Advanced Solid Tumors (Phase 1); Diffuse Large B-cell Lymphoma (Phase 2); Follicular Lymphoma (Phase 2); Transformed Follicular Lymphoma; Primary Mediastinal Large B-Cell Lymphoma

  18. Detection and outcome of occult leptomeningeal disease in diffuse large B-cell lymphoma and Burkitt lymphoma.

    Science.gov (United States)

    Wilson, Wyndham H; Bromberg, Jacoline E C; Stetler-Stevenson, Maryalice; Steinberg, Seth M; Martin-Martin, Lourdes; Muñiz, Carmen; Sancho, Juan Manuel; Caballero, Maria Dolores; Davidis, Marjan A; Brooimans, Rik A; Sanchez-Gonzalez, Blanca; Salar, Antonio; González-Barca, Eva; Ribera, Jose Maria; Shovlin, Margaret; Filie, Armando; Dunleavy, Kieron; Mehrling, Thomas; Spina, Michele; Orfao, Alberto

    2014-07-01

    The benefit of intrathecal therapy and systemic rituximab on the outcome of diffuse large B-cell lymphoma at risk of central nervous system disease is controversial. Furthermore, the effect of intrathecal treatment and rituximab in diffuse large B-cell and Burkitt lymphoma with occult leptomeningeal disease detected by flow cytometry at diagnosis is unknown. Untreated diffuse large B-cell (n=246) and Burkitt (n=80) lymphoma at clinical risk of central nervous system disease and having had pre-treatment cerebrospinal fluid were analyzed by flow cytometry and cytology. Spinal fluid involvement was detected by flow cytometry alone (occult) in 33 (13%) diffuse large B-cell and 9 (11%) Burkitt lymphoma patients, and detected by cytology in 11 (4.5%) and 5 (6%) patients, respectively. Diffuse large B-cell lymphoma with occult spinal fluid involvement had poorer survival (P=0.0001) and freedom from central nervous system relapse (Pdisease and not control of central nervous system disease was the principal cause of treatment failure. In diffuse large B-cell lymphoma, systemic rituximab was associated with improved freedom from central nervous system relapse (P=0.003) but not with survival. Our results suggest that patients at risk of central nervous system disease should be evaluated by flow cytometry and that intrathecal prophylaxis/therapy is beneficial.

  19. Outcome of children and adolescents with lymphoblastic lymphoma

    Directory of Open Access Journals (Sweden)

    Maria Christina Lopes Araújo Oliveira

    2015-10-01

    Full Text Available Summary Introduction: lymphoblastic lymphoma (LBL is the second most common subtype of non-Hodgkin lymphoma in children. The aim of this study was to characterize the clinical course of children and adolescents with LBL treated at a tertiary center. Methods: this is a retrospective cohort study of 27 patients aged 16 years or younger with LBL admitted between January 1981 and December 2013. Patients were treated according to the therapy protocol used for acute lymphoblastic leucemia. Diagnosis was based on biopsy of tumor and/or cytological examination of pleural effusions. The overall survival was analyzed using the Kaplan-Meier method. Results: the median age at diagnosis was 11.6 years (interquartile range, 4.6- 13.8. LBL had T-cell origin in 16 patients (59%. The most common primary manifestation in T-cell LBL was mediastinal involvement, in 9 patients (56%. Intra-abdominal tumor was the major site of involvement in patients with precursor B-LBL. Most patients had advanced disease (18 patients – 67% at diagnosis. Twenty-four patients (89% achieved complete clinical remission. After a median follow-up of 43 months (interquartile range, 6.4-95, 22 patients (81% were alive in first complete remission. Five children (18.5% died, three of them soon after admission and two after relapsing. The probability of survival at five years for 20 patients with de novo LBL was 78% (SD 9.4. Conclusion: our findings confirm the favorable prognosis of children with LBL with an intensive chemotherapy regimen derived from ALL therapy.

  20. Diagnostic value of immunoglobulin κ light chain gene rearrangement analysis in B-cell lymphomas.

    Science.gov (United States)

    Kokovic, Ira; Jezersek Novakovic, Barbara; Novakovic, Srdjan

    2015-03-01

    Analysis of the immunoglobulin κ light chain (IGK) gene is an alternative method for B-cell clonality assessment in the diagnosis of mature B-cell proliferations in which the detection of clonal immunoglobulin heavy chain (IGH) gene rearrangements fails. The aim of the present study was to evaluate the added value of standardized BIOMED-2 assay for the detection of clonal IGK gene rearrangements in the diagnostic setting of suspected B-cell lymphomas. With this purpose, 92 specimens from 80 patients with the final diagnosis of mature B-cell lymphoma (37 specimens), mature T-cell lymphoma (26 specimens) and reactive lymphoid proliferation (29 specimens) were analyzed for B-cell clonality. B-cell clonality analysis was performed using the BIOMED-2 IGH and IGK gene clonality assays. The determined sensitivity of the IGK assay was 67.6%, while the determined sensitivity of the IGH assay was 75.7%. The sensitivity of combined IGH+IGK assay was 81.1%. The determined specificity of the IGK assay was 96.2% in the group of T-cell lymphomas and 96.6% in the group of reactive lesions. The determined specificity of the IGH assay was 84.6% in the group of lymphomas and 86.2% in the group of reactive lesions. The comparison of GeneScan (GS) and heteroduplex pretreatment-polyacrylamide gel electrophoresis (HD-PAGE) methods for the analysis of IGK gene rearrangements showed a higher efficacy of GS analysis in a series of 27 B-cell lymphomas analyzed by both methods. In the present study, we demonstrated that by applying the combined IGH+IGK clonality assay the overall detection rate of B-cell clonality was increased by 5.4%. Thus, we confirmed the added value of the standardized BIOMED-2 IGK assay for assessment of B-cell clonality in suspected B-cell lymphomas with inconclusive clinical and cyto/histological diagnosis.

  1. Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Yuan-Fang Liu

    2016-06-01

    Full Text Available Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice. Eight gene expression subgroups associated with characteristic genetic abnormalities were identified, including leukemia with MEF2D and ZNF384 fusions in two distinct clusters. In subgroup G4 which was characterized by ERG deletion, DUX4-IGH fusion was detected in most cases. This comprehensive dataset allowed us to compare the features of molecular pathogenesis between adult and pediatric B-ALL and to identify signatures possibly related to the inferior outcome of adults to that of children. We found that, besides the known discrepancies in frequencies of prognostic markers, adult patients had more cooperative mutations and greater enrichment for alterations of epigenetic modifiers and genes linked to B-cell development, suggesting difference in the target cells of transformation between adult and pediatric patients and may explain in part the disparity in their responses to treatment.

  2. Immunohistochemical patterns of follicular dendritic cell meshwork and Ki-67 in small B-cell lymphomas

    Institute of Scientific and Technical Information of China (English)

    时云飞

    2013-01-01

    Objective To identify the immunohistochemical patterns of follicular dendritic cell(FDC)meshwork and Ki-67labeling index in small B-cell lymphomas(SBLs) and their significance in differential diagnosis.Methods

  3. Antigen selection in B-cell lymphomas--tracing the evidence.

    Science.gov (United States)

    Sutton, Lesley-Ann; Agathangelidis, Andreas; Belessi, Chrysoula; Darzentas, Nikos; Davi, Frederic; Ghia, Paolo; Rosenquist, Richard; Stamatopoulos, Kostas

    2013-12-01

    While signaling through the B cell receptor (BcR) facilitates B cell development and maintenance, it also carries intertwined risks for the development of lymphomas since malignant B cells can exploit these pathways in order to trigger and fuel clonal expansion. This corruption of the normal B cell response to antigens, leading to sustained BcR signaling, has given great impulse to investigate in detail the role of antigen in lymphomas. Suffice it to conclude from such studies, largely immunogenetics based, that the evidence implicating antigens (exogenous or self) in lymphoma development is substantial and that lymphomagenesis is functionally driven and dynamic, rather than a simple stochastic process. As the paradigm of antigen-driven lymphoma evolves, further investigation will be paramount to the identification of the inciting agent(s) that may be responsible for immunoproliferative neoplasms and also for the development of therapeutic agents targeting effectors of the BcR signaling pathway.

  4. Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by CART19

    Science.gov (United States)

    2016-01-26

    Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  5. The predictive significance of CD20 expression in B-cell lymphomas

    Directory of Open Access Journals (Sweden)

    Horvat Mateja

    2011-04-01

    Full Text Available Abstract Background In our recent study, we determined the cut-off value of CD20 expression at the level of 25 000 molecules of equivalent soluble fluorochrome (MESF to be the predictor of response to rituximab containing treatment in patients with B-cell lymphomas. In 17.5% of patients, who had the level of CD20 expression below the cut-off value, the response to rituximab containing treatment was significantly worse than in the rest of the patients with the level of CD20 expression above the cut-off value. The proportion of patients with low CD20 expression who might not benefit from rituximab containing treatment was not necessarily representative. Therefore the aim of this study was to quantify the CD20 expression in a larger series of patients with B-cell lymphomas which might allow us to determine more reliably the proportion of patients with the CD20 expression below the cut-off. Methods Cytological samples of 64 diffuse large B-cell lymphomas (DLBCL, 56 follicular lymphomas (FL, 31 chronic lymphocytic leukemias (CLL, 34 mantle cell lymphomas (MCL, 18 marginal zone lymphomas (MZL and 15 B-cell lymphomas unclassified were analyzed for CD20 expression by quantitative four-color flow cytometric measurements using FACSCalibur flow cytometer (BD Biosciences. Results The range of CD20 expression in different B-cell lymphomas was very broad, varying from 2 737 to 115 623 MESF in CLL and 3 549 to 679 577 MESF in DLBCL. However, when we compared the CD20 expression in the groups of patients with DLBCL, FL, MCL, MZL, CLL and B-cell lymphomas unclassified, it was found to be significantly lower (p = 0.002 only in CLL but did not significantly differ in other lymphoma types (p = NS. Fifty-three out of 218 (24.3% patients with B-cell lymphomas had the CD20 expression below the cut-off value. Conclusions The CD20 expression in CLL is significantly lower than in most histological types of mature B-cell lymphomas in which it appears to be comparable

  6. Metastatic Calcinosis Cutis: A Case in a Child with Acute Pre-B Cell Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Juan Pablo Castanedo-Cázares

    2015-01-01

    Full Text Available Hypercalcemia in children with malignancy is an uncommon condition. It has been described in leukemia patients with impaired renal excretion of calcium or osteolytic lesions. Metastatic calcinosis cutis (MCC may develop if hypercalcemia persists. We report the case of a 5-year-old girl with an atypical dermatosis and unspecific gastrointestinal symptoms. Considered clinical diagnoses were xanthomas, histiocytosis, molluscum contagiosum, and nongenital warts. Cutaneous histological analysis showed amorphous basophilic deposits in the dermis suggestive of calcium deposits. Laboratory tests confirmed serum hypercalcemia. Extensive investigations such as bone marrow biopsy established the diagnosis of an acute pre-B cell lymphoblastic leukemia. Hypercalcemia in hematopoietic malignancies is unusual, especially as initial manifestation of the disease. Careful review of the literature fails to reveal previous reports of these peculiar cutaneous lesions of MCC in children with leukemia.

  7. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    A. Sanjuan-Pla (Alejandra); C. Bueno (C.); C. Prieto (Cristina); P. Acha (Pamela); R.W. Stam (Ronald); R. Marschalek (Rolf); P. Menéndez (Pablo)

    2015-01-01

    textabstractInfant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinicalmanagement and survival (∼85-90%) of childhood B-ALL,

  8. Primary B-cell Lymphoma of the Thyroid Featuring the Different Ultrasonographic Findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Na; Choi, Yoon Jung; Kim, Dong Hoon [Kangbuk Samsung Medical Center, Seoul (Korea, Republic of)

    2009-06-15

    We review here 3 cases of primary thyroid lymphoma that we experienced during the past 5 years (age range: 39-55, all of the patients were female). The clinical and various ultrasonographic characteristics together with the other imaging modalities of primary thyroid lymphomas are described. The clinical features at presentation for one patient were a goiter with rapid growth and this was accompanied by compressive symptoms. The tumors of the other 2 patients were incidentally found during screening thyroid ultrasound exams. The pathologic studies of 2 cases showed a diffuse B-cell lymphoma with associated Hashimoto's thyroiditis and one case was a B-cell lymphoma of the MALT type. An extra-thyroid extension was shown in one case. The treatments included surgery alone for two cases, and chemotherapy and radiation therapy for one case. A US exam of thyroid lymphoma can show various morphological features, and US-CNB is helpful for diagnosing thyroid lymphoma.

  9. Coexistent Nodal Diffuse Large B-Cell Lymphoma With Extrapulmonary Tuberculosis: A Rare Case.

    Science.gov (United States)

    Sachdev, Ritesh; Duggal, Rajan; Agrawal, Krati; Goel, Shalini

    2016-02-01

    Extrapulmonary tuberculosis coexistent with lymphomas in the same organ are rare and have been reported in the literature. The most common organs that are involved are small bowel, bronchus, kidney, and lymph nodes. Interestingly, the lymphoma that is commonly present with extrapulmonary tuberculosis is Hodgkin's lymphoma followed by low-grade non-Hodgkin's lymphoma. In the present study, we report a 60-year-old man with complaints of fever, loss of appetite, and generalized weakness. On investigation, generalized lymphadenopathy was noted, and the biopsy of cervical lymph node revealed coexistence of diffuse large B-cell lymphoma with extrapulmonary tuberculosis. This case is the second reported case of diffuse large B-cell lymphoma with extrapulmonary tuberculosis in the world and the first in India.

  10. Frequent disruption of the RB1 pathway in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Møller, M B; Kania, Per Walter; Ino, Y

    2000-01-01

    In the present study, we analysed 34 de novo diffuse large B cell lymphoma (DLCL) from a population-based lymphoma registry for alterations of the RB1 pathway at the genetic (RB1 and CDK4) and protein (pRb, cyclin D1, cyclin D3, CDK4, and E2F-1) level. The results were correlated with the data fr...

  11. Relationships among hepatitis C virus, hepatocellular carcinoma, and diffuse large B cell lymphoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Hyuk Jun; Kim, Seong Hoon [Dept. of Radiology, Daegu Fatima Hospital, Daegu (Korea, Republic of)

    2015-07-15

    Hepatitis C virus (HCV) is one of the main causes of hepatocellular carcinoma (HCC). Recent studies have reported various associations between HCV and the incidence of non-Hodgkin's lymphoma. We report the radiologic findings in a rare case of simultaneous occurrence of HCC and diffuse large B cell lymphoma in a HCV carrier.

  12. Primary thymic extranodal marginal zone B cell lymphoma as an incidental finding in a Caucasian woman

    DEFF Research Database (Denmark)

    Krogh Petersen, Jeanette; Larsen, Thomas Stauffer; Møller, Michael Boe

    2015-01-01

    Primary thymic extranodal marginal zone B cell lymphoma (TML) is an extremely rare lymphoma strongly associated with autoimmune disease. We report an exceedingly rare case of TML found in a non-Asian population. TML was found incidentally in a 60-year-old Caucasian woman with a short history...

  13. Reactivation of hepatitis D virus after chemotherapy for diffuse large B cell lymphoma despite lamivudine prophylaxis

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Gerstoft, Jan; Weis, Nina Margrethe

    2010-01-01

    We describe a case of reactivation of hepatitis D virus (HDV) in a patient treated with chemotherapy for a diffuse large B cell lymphoma despite lamivudine prophylaxis. This case suggests that previously cleared HDV should be considered when administering chemotherapy to patients with lymphoma....

  14. Chronic inflammatory disease, lymphoid tissue neogenesis and extranodal marginal zone B-cell lymphomas

    NARCIS (Netherlands)

    R.J. Bende; F. van Maldegem; C.J.M. van Noesel

    2009-01-01

    Chronic autoimmune or pathogen-induced immune reactions resulting in lymphoid neogenesis are associated with development of malignant lymphomas, mostly extranodal marginal zone B-cell lymphomas (MZBCLs). In this review we address (i) chemokines and adhesion molecules involved in lymphoid neogenesis;

  15. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

    NARCIS (Netherlands)

    Cerhan, James R.; Berndt, Sonja I.; Vijai, Joseph; Ghesquières, Hervé; McKay, James; Wang, Sophia S.; Wang, Zhaoming; Yeager, Meredith; Conde, Lucia; De Bakker, Paul I W; Nieters, Alexandra; Cox, David; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R.; De Roos, Anneclaire J.; Brooks-Wilson, Angela R.; Lan, Qing; Severi, Gianluca; Melbye, Mads; Gu, Jian; Jackson, Rebecca D.; Kane, Eleanor; Teras, Lauren R.; Purdue, Mark P.; Vajdic, Claire M.; Spinelli, John J.; Giles, Graham G.; Albanes, Demetrius; Kelly, Rachel S.; Zucca, Mariagrazia; Bertrand, Kimberly A.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M.; Link, Brian K.; Novak, Anne J.; Dogan, Ahmet; Asmann, Yan W.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.; Weiner, George J.; Veron, Amelie S.; Zelenika, Diana; Tilly, Hervé; Haioun, Corinne; Molina, Thierry Jo; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans Olov; Bracci, Paige M.; Riby, Jacques; Smith, Martyn T.; Holly, Elizabeth A.; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Tinker, Lesley F.; North, Kari E.; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W. Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.; Villano, Danylo J.; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Kricker, Anne; Turner, Jenny; Southey, Melissa C.; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Trichopoulos, Dimitrios; Vermeulen, Roel C H; Boeing, Heiner; Tjonneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; Birmann, Brenda M.; Laden, Francine; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Sampson, Joshua; Liang, Liming; Park, Ju Hyun; Chung, Charles C.; Weisenburger, Dennis D.; Chatterjee, Nilanjan; Fraumeni, Joseph F.; Slager, Susan L.; Wu, Xifeng; De Sanjose, Silvia; Smedby, Karin E.; Salles, Gilles; Skibola, Christine F.; Rothman, Nathaniel; Chanock, Stephen J.

    2014-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of Euro

  16. Ocular Adnexal Diffuse Large B-cell LymphomaA Multicenter International Study

    DEFF Research Database (Denmark)

    Munch-Petersen, Helga D; Rasmussen, Peter K; Coupland, Sarah E

    2015-01-01

    IMPORTANCE: The clinical features of diffuse large B-cell lymphoma (DLBCL) subtype of ocular adnexal lymphoma have not previously been evaluated in a large cohort to our knowledge. OBJECTIVE: To investigate the clinical features of ocular adnexal DLBCL (OA-DLBCL). DESIGN, SETTING, AND PARTICIPANT...

  17. Antecedent presentation of aplastic anemia in a patient with diffuse large B cell lymphoma

    Directory of Open Access Journals (Sweden)

    Chien-Ting Chen

    2016-12-01

    Full Text Available Immunological manifestation occasionally develops concurrently with lymphoid neoplasms, including immune thrombocytopenia and autoimmune hemolytic anemia, but rarely reported acquired aplastic anemia (AA. Here we present a female case of diffuse large B cell lymphoma (DLBCL with antecedent presentation of AA. Recovery of AA was noted after complete response to lymphoma treatment. Literature regarding this issue was reviewed.

  18. Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals

    NARCIS (Netherlands)

    Limpens, J; Stad, R; Vos, C; de Vlaam, C; de Jong, D; van Ommen, G J; Schuuring, E; Kluin, P M

    1995-01-01

    Successive oncogenic steps are necessary to generate cancer. In many B-cell lymphomas, chromosomal translocations are considered to be an early oncogenic hit. We investigated whether the lymphoma-associated t(14;18) involving the BCL2 oncogene can occur outside the context of malignancy. To this end

  19. B-cell lymphoma of the appendix: A case report and review of literature

    OpenAIRE

    Jagannath Dev Sharma; C. Chonzik; Tonmoy Das; Manigreeva Krishnatreya

    2014-01-01

    Appendicular tumors are rare, and lymphoma of the appendix is rarer. A 50 - year - old female patient presented with vague abdominal discomfort and lump in the right iliac fossa. The diagnosis of diffuse large B - cell lymphoma was made after laparotomy and histopathological examination (HPE) supported by immunohistochemistry study. For appendicular neoplasms diagnosed postoperatively, including lymphoma, a meticulous grossing and HPE cannot be over emph...

  20. Primary gastric T cell lymphoma mimicking marginal zone B cell lymphoma of mucosa-associated lymphoid tissue.

    Science.gov (United States)

    Holanda, Danniele; Zhao, Merry Y; Rapoport, Aaron P; Garofalo, Michael; Chen, Qing; Zhao, X Frank

    2008-07-01

    Primary gastric T cell lymphoma is rare and mostly of large cell type. In this paper, we present a case of gastric T cell lymphoma morphologically similar to the gastric marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT). Morphologically, the cells are small with abundant clear cytoplasm. Lymphoepithelial lesions are readily identified with diffuse destruction of gastric glands. Immunohistochemically, the neoplastic cells are CD3+/CD4+/CD8-/Granzyme B-. Molecular studies revealed monoclonal T cell receptor gamma gene rearrangement. Clinically, the patient responded initially to four cycles of R-CHOP, but then progressed. Because peripheral T cell lymphoma is usually associated with a poor prognosis, whereas marginal zone B cell lymphoma is an indolent lymphoproliferative disorder, this morphologic mimicry should be recognized and completely investigated when atypical small lymphoid infiltrates with lymphoepithelial lesions are encountered in the stomach.

  1. Diffuse large B-cell lymphoma with combined TP53 mutation and MIR34A> methylation

    DEFF Research Database (Denmark)

    Asmar, Fazila; Hother, Christoffer; Kulosman, Gorjan;

    2014-01-01

    MiR34A, B and C have been implicated in lymphomagenesis, but information on their role in normal CD19+ B-cells (PBL-B) and de novo diffuse large B-cell lymphoma (DLBCL) is limited. We show that in normal and activated B-cells miR34A-5p plays a dominant role compared to other miR34 family members....

  2. Burkitt's lymphoma is a malignancy of mature B cells expressing somatically mutated V region genes.

    OpenAIRE

    Klein, U.; Klein, G.; Ehlin-Henriksson, B.; Rajewsky, K.; Küppers, R.

    1995-01-01

    BACKGROUND: The developmental stage from which stems the malignant B cell population in Burkitt's lymphoma (BL) is unclear. An approach to answering this question is provided by the sequence analysis of rear-ranged immunoglobulin (Ig) variable region (V) genes from BL for evidence of somatic mutations, together with a phenotypic characterization. As somatic hypermutation of Ig V region genes occurs in germinal center B cells, somatically mutated Ig genes are found in germinal center B cells a...

  3. TET2 promoter DNA methylation and expression analysis in pediatric B-cell acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ewa Musialik

    2014-03-01

    Full Text Available TET2 is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin. Besides loss-of-function mutations and deletions, hypermethylation of the CpG island at the TET2 promoter was found in human cancer. Previous analysis revealed no TET2 mutations in acute lymphoblastic leukemia (ALL. Since the TET2 promoter methylation status in pediatric ALL has not been reported, the aim of the present study was to determine if promoter hypermethylation may be a mechanism of TET2 inactivation in a group of pediatric ALL cases. Methylation of TET2 promoter region in one (1/45 ALL B-common patient was detected by methylation specific polymerase chain reaction (PCR and subsequently analyzed by bisulfite sequencing. We found no correlation between promoter methylation and gene expression, measured by quantitative reverse transcriptase-PCR, however the level of TET2 expression in ALL group was significantly decreased compared to children’s normal peripheral blood mononuclear cells and isolated B-cells. TET2 promoter hypermethylation seems to have limited clinical relevance in childhood B-cell ALL due to its low frequency.

  4. Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

    Science.gov (United States)

    2015-05-06

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I AIDS-related Lymphoma; Stage II AIDS-related Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  5. Early B-cell Specific Inactivation of ATM Synergizes with Ectopic CyclinD1 Expression to Promote Pre-germinal center B-cell Lymphomas in Mice

    Science.gov (United States)

    Yamamoto, Kenta; Lee, Brian J.; Li, Chen; Dubois, Richard L.; Hobeika, Elias; Bhagat, Govind; Zha, Shan

    2017-01-01

    Ataxia Telangiectasia Mutated (ATM) kinase is a master regulator of the DNA damage response. ATM is frequently inactivated in human B-cell non-Hodgkin Lymphomas (B-NHL), including ~50% of mantle cell lymphomas (MCLs) characterized by ectopic expression of CyclinD1. Here we report that early and robust deletion of ATM in precursor/progenitor B-cells causes cell-autonomous, clonal mature B cell lymphomas of both pre- and post-germinal center (GC) origins. Unexpectedly naïve B cell specific deletion of ATM is not sufficient to induce lymphomas in mice, highlighting the important tumor suppressor function of ATM in immature B cells. While EμCyclinD1 is not sufficient to induce lymphomas, EμCyclinD1 accelerates the kinetics and increased the incidence of clonal lymphomas in ATM-deficient B-cells and skews the lymphomas towards pre-GC derived small lymphocytic neoplasms sharing morphological features of human MCL. This is in part due to CyclinD1-driven expansion of ATM-deficient naïve B cells with genomic instability, which promotes the deletions of additional tumor suppressor genes (i.g. Trp53, Mll2, Rb1 and Cdkn2a). Together these findings define a synergistic function of ATM and CyclinD1 in pre-germinal center B-cell proliferation and lymphomagenesis and provide a prototypic animal model to study the pathogenesis of human MCL. PMID:25676421

  6. Early B-cell-specific inactivation of ATM synergizes with ectopic CyclinD1 expression to promote pre-germinal center B-cell lymphomas in mice.

    Science.gov (United States)

    Yamamoto, K; Lee, B J; Li, C; Dubois, R L; Hobeika, E; Bhagat, G; Zha, S

    2015-06-01

    Ataxia telangiectasia-mutated (ATM) kinase is a master regulator of the DNA damage response. ATM is frequently inactivated in human B-cell non-Hodgkin lymphomas, including ~50% of mantle cell lymphomas (MCLs) characterized by ectopic expression of CyclinD1. Here we report that early and robust deletion of ATM in precursor/progenitor B cells causes cell autonomous, clonal mature B-cell lymphomas of both pre- and post-germinal center (GC) origins. Unexpectedly, naive B-cell-specific deletion of ATM is not sufficient to induce lymphomas in mice, highlighting the important tumor suppressor function of ATM in immature B cells. Although EμCyclinD1 is not sufficient to induce lymphomas, EμCyclinD1 accelerates the kinetics and increases the incidence of clonal lymphomas in ATM-deficient B-cells and skews the lymphomas toward pre-GC-derived small lymphocytic neoplasms, sharing morphological features of human MCL. This is in part due to CyclinD1-driven expansion of ATM-deficient naive B cells with genomic instability, which promotes the deletions of additional tumor suppressor genes (i.e. Trp53, Mll2, Rb1 and Cdkn2a). Together these findings define a synergistic function of ATM and CyclinD1 in pre-GC B-cell proliferation and lymphomagenesis and provide a prototypic animal model to study the pathogenesis of human MCL.

  7. [Primary colorectal lymphoma of diffuse large B-cells: an experience at a general hospital].

    Science.gov (United States)

    Beltran Gárate, Brady; Morales Luna, Domingo; Quiñones Avila, Pilar; Hurtado de Mendoza, Fernando; Riva Gonzales, Luis; Yabar, Alejandro; Portugal Meza, Karem

    2008-01-01

    Primary colorectal lymphoma is a very rare disease. Primary colorectal lymphoma of diffuse large B-cells is a more frequent subtype representing 1% of all colon diseases. In a retrospective study, the clinical characteristics and treatment course of primary colorectal lymphoma of diffuse large B-cells between 1997 and 2003 were reviewed. According to Dawson's criteria, fourteen cases were identified. The average age was 65 and the ratio of men to women was 1:3. The most frequent signs and symptoms were abdominal pain (78%), diarrhea (49%) and abdominal tumor (35%). The most frequently involved regions were the cecum (42%), ascending colon (21%) and rectum (21%). Six were in Stage I, four in Stage II and four in Stage III. The 5-year survival per stage was 26, 11 and 5 months, respectively. Primary colorectal lymphoma of diffuse large B-cells usually affects the right part of the colon in an aggressive manner.

  8. Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Ye, Qing; Xu-Monette, Zijun Y; Tzankov, Alexandar;

    2016-01-01

    and BCL6 in 898 patients with de novo diffuse large B-cell lymphoma treated with standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab). Neither BCL6 translocation alone (more frequent in activated B-cell like diffuse large B-cell lymphoma) nor in combination...

  9. A Case of p63 Positive Diffuse Large B Cell Lymphoma of the Bladder

    Science.gov (United States)

    Jones, Carol

    2016-01-01

    Diffuse large B cell lymphoma (DLBCL), currently the most common type of non-Hodgkin lymphoma (NHL), is an aggressive B cell neoplasm that typically presents in older adults as a rapidly enlarging mass. The enlarging mass typically represents a lymph node, although extranodal disease can occur in a significant percentage (40%) of cases. The most common extranodal sites of involvement include the gastrointestinal tract and skin; primary bladder lymphoma represents only 0.2% of extranodal non-Hodgkin lymphomas. We report a case of diffuse large B cell lymphoma occurring in the bladder of an 83-year-old gentleman with an initial presentation of hematuria. This neoplasm displayed large, atypical cells with vesicular chromatin and prominent nucleoli that involved the bladder mucosa with invasion into muscularis propria, prostate, and urethra. Positive staining for p63 initially raised suspicion for poorly differentiated urothelial carcinoma; however, lack of staining for pancytokeratin and positive staining for LCA, CD20, CD79a, and PAX-5 confirmed the diagnosis of diffuse large B cell lymphoma. Though it does not occur in all cases, p63 can be positive in a significant percentage of cases of DLBCL; therefore, a diagnosis of lymphoma remains an important entity on the differential diagnosis of aggressive and particularly poorly differentiated neoplasms. PMID:27648316

  10. Epigenetic inactivation of Notch-Hes pathway in human B-cell acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Shao-Qing Kuang

    Full Text Available The Notch pathway can have both oncogenic and tumor suppressor roles, depending on cell context. For example, Notch signaling promotes T cell differentiation and is leukemogenic in T cells, whereas it inhibits early B cell differentiation and acts as a tumor suppressor in B cell leukemia where it induces growth arrest and apoptosis. The regulatory mechanisms that contribute to these opposing roles are not understood. Aberrant promoter DNA methylation and histone modifications are associated with silencing of tumor suppressor genes and have been implicated in leukemogenesis. Using methylated CpG island amplification (MCA/DNA promoter microarray, we identified Notch3 and Hes5 as hypermethylated in human B cell acute lymphoblastic leukemia (ALL. We investigated the methylation status of other Notch pathway genes by bisulfite pyrosequencing. Notch3, JAG1, Hes2, Hes4 and Hes5 were frequently hypermethylated in B leukemia cell lines and primary B-ALL, in contrast to T-ALL cell lines and patient samples. Aberrant methylation of Notch3 and Hes5 in B-ALL was associated with gene silencing and was accompanied by decrease of H3K4 trimethylation and H3K9 acetylation and gain of H3K9 trimethylation and H3K27 trimethylation. 5-aza-2'-deoxycytidine treatment restored Hes5 expression and decreased promoter hypermethylation in most leukemia cell lines and primary B-ALL samples. Restoration of Hes5 expression by lentiviral transduction resulted in growth arrest and apoptosis in Hes5 negative B-ALL cells but not in Hes5 expressing T-ALL cells. These data suggest that epigenetic modifications are implicated in silencing of tumor suppressor of Notch/Hes pathway in B-ALL.

  11. Detection of germinal center B-cell lymphoma in archival specimens: critical evaluation of Bcl-6 protein expression in diffuse large B-cell lymphoma of the tonsil.

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    Ree, Howe J; Ohsima, Koichi; Aozasa, Katsuyuki; Takeuchi, Kengo; Kim, Chul Woo; Yang, Woo Ick; Huh, Joor Yung; Lee, Seung-Sook; Ko, Yong-Hye; Kwon, Mi Seon; Cho, Eun Yoon; Choi, Yoon-La; Rhee, Jong Chul; Kikuchi, Masahiro; Mori, Shigeo

    2003-06-01

    Expression of Bcl-6 and CD10, markers for the tumor of the germinal center (GC) B-cell derivation, has been studied in primary diffuse large B-cell lymphomas (DLBCLs) of the lymph node, gastrointestinal tract, and mediastinum. In these studies, the coexpression rate of CD10 and Bcl-6 was relatively constant at 30% approximately 40%, but the frequency of Bcl-6+ tumors varied from 55% to 100%, raising doubts about the usefulness of Bcl-6 expression in identifying the tumor of GC B-cell derivation. Because the expression of Bcl-6 in tumors of non-GC B-cell origin has recently been reported, we critically evaluated the expression of Bcl-6 and CD10 in primary DLBCLs of the tonsil, a relatively common tumor in Japan and Korea. The cases (n = 51) represented a consecutive series for any recent 2-year period at several teaching hospitals in Korea and Japan. Formalin-fixed, paraffin-embedded specimens were used for immunostaining. Staining for Bcl-6 and CD10 was positive in 44 (86%) and 22 cases (45%), respectively. However, among those positive for Bcl-6 (>10% Bcl-6+ tumor cells), 2 basic patterns were recognized: uniform and nonuniform. The uniform pattern was characterized by a dense population (>75%) and a consistent density in any given area, resembling the staining pattern observed in GC or follicular lymphoma (FL) (the "GC/FL" pattern). In contrast, the nonuniform pattern exhibited a varying density from area to area, as well as a less-dense population (51%). All but 1 (95%) of the CD10+ tumors coexpressed Bcl-6, with most (82%) displaying the uniform pattern. We conclude that tumors showing a uniform pattern of Bcl-6 expression should be distinguished from those showing a nonuniform pattern, because the former most likely represent tumors of GC B-cell derivation and the latter most likely represent tumors of non-GC derivation. GC B-cell lymphoma thus defined accounted for 51% of tonsillar DLBCL, a proportion comparable to that of the nodal DLBCL. CD10 expression

  12. B-cell lymphoma of the appendix: A case report and review of literature

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    Jagannath Dev Sharma

    2014-08-01

    Full Text Available Appendicular tumors are rare, and lymphoma of the appendix is rarer. A 50 - year - old female patient presented with vague abdominal discomfort and lump in the right iliac fossa. The diagnosis of diffuse large B - cell lymphoma was made after laparotomy and histopathological examination (HPE supported by immunohistochemistry study. For appendicular neoplasms diagnosed postoperatively, including lymphoma, a meticulous grossing and HPE cannot be over emphasized. In case of wall thickening of >2.50- 3 cm detected by the computed tomogram scan, the possibility of a neoplasm or lymphoma in particular should be included as the differential diagnosis irrespective of the clinical presentation

  13. Primary mediastinal large B-cell lymphoma arising from thyroid in a renal recipient with Hashimoto's thyroiditis.

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    Wu, Fang; Qu, Lu; Li, Dai-Qiang; Hu, Chun-Hong

    2015-01-01

    Primary mediastinal large B-cell lymphoma is a subtype of diffuse large B-cell lymphoma, arising in the mediastinum from putative thymic B-cell origin with distinctive clinical and genetic features. Generally, primary mediastinal large B-cell lymphoma is believed as only deriving in the mediastinum. The current study presents a rare case of primary mediastinal large B-cell lymphoma which arising from thyroid in a renal recipient with Hashimoto's thyroiditis. Moreover, we devoted a discussion to the relationship among primary mediastinal large B-cell lymphoma, immunomodulatory therapy and autoimmune diseases. The immunologic derangement induced by long-term immunomodulatory therapy and Hashimoto's thyroiditis may be the possible cause for the ectopic lymphoma.

  14. Primary diffuse large B cell lymphoma developing at the ileocolonic anastomosis site after right hemicolectomy for adenocarcinoma: A case report

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    Oh, Hye Yeon; Choi, Seung Joon; Kim, Hyung Sik; Kim, Jeong Ho; Choi, Hye Young [Dept. of Radiology, Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2014-04-15

    Lymphoma is rarely associated with ileocolonic surgery. We report the imaging findings of primary diffuse large B-cell lymphoma arising in an ileocolonic anastomosis site, found five years after a right hemicolectomy for adenocarcinoma in the ascending colon.

  15. Two cases of uveitis masquerade syndrome caused by bilateral intraocular large B-cell lymphoma

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    Jovanović Svetlana

    2013-01-01

    Full Text Available Introduction. Sometimes it is not easy to clinically recognize subtle differences between intraocular lymphoma and noninfectious uveitis. The most common lymphoma subtype involving the eye is B-cell lymphoma. Case report. We presented two patients aged 59 and 58 years with infiltration of the subretinal space with a large B-cell non-Hodgkin intraocular lymphoma. The patients originally had clinically masked syndrome in the form of intermediate uveitis. As it was a corticosteroid-resistant uveitis, we focused on the possible diagnosis of neoplastic causes of this syndrome. During hospitalization, the neurological symptoms emerged and multiple subretinal changes accompanied by yellowish white patches of retinal pigment epithelium with signs of vitritis, which made us suspect the intraocular lymphoma. Endocranial magnetic resonance imaging established tumorous infiltration in the region of the left hemisphere of the cerebellum. The histopathological finding confirmed the diagnosis of large B-cell non-Hodgkin lymphoma of risk moderate degree, immunoblast - centroblast cytological type. The other patient had clinical chronic uveitis accompanied by yellowish shaped white echographic changes of the retina and localized changes in the level of the subretina. The diagnosis of lymphoma was made by brain biopsy. Conclusion. Uveitis masquerade syndrome should be considered in all patients over 40 years with idiopathic steroid-resistant uveitis. Treatment begun on time can affect the course and improve the prognosis of uveitis masquerade syndrome (UMS and systemic disease.

  16. A Case of Successful Remission of Extensive Primary Gastric Diffuse Large B Cell Lymphoma: Radiologic, Endoscopic and Pathologic Evidence

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    Mike M. Bismar

    2014-04-01

    Full Text Available Though rare amongst stomach neoplasms, primary gastric diffuse large B cell lymphoma is one of the commonest extranodal non-Hodgkin lymphomas. If left untreated, it can have a devastating progression and life-threatening consequences. We present the case of a successfully treated large antral ulcer confirmed to be large B cell lymphoma as evidenced by radiologic, endoscopic and histopathologic findings. A brief discussion about the types of gastric lymphoma, their Helicobacter pylori relation and therapeutic modalities follows.

  17. High throughput tissue microarray analysis of FHIT expression in diffuse large cell B-cell lymphoma from Saudi Arabia.

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    Al Kuraya, Khawla; Siraj, Abdul Khalid; Bavi, Prashant; Al-Jomah, Naif; El-Solh, Hassan; Ezzat, Adnan; Al-Dayel, Fouad; Belgaumi, Asim; Al-Kofide, Amani; Sabbah, Rajeh; Sheikh, Salwa; Amr, Samir; Simon, Ronald; Sauter, Guido

    2006-08-01

    Recent studies have suggested a potential prognostic role of alterations of the fragile histidine triad (FHIT) gene in diffuse large B-cell lymphoma. To evaluate possible mechanisms of FHIT inactivation and to further clarify its potential prognostic relevance, we analyzed a set of 114 diffuse large B-cell lymphoma with clinical follow-up information. Tissue microarrays were analyzed by immunohistochemistry for protein expression, and corresponding DNA samples were analyzed for FHIT promotor hypermethlyation. Reduced or absent FHIT expression was found in 75 of 114 diffuse large B-cell lymphoma (66%), but was unrelated to clinical tumor stage or patient prognosis. FHIT promotor hypermethylation was observed in 29 of 93 (23%) interpretable diffuse large B-cell lymphoma. Hypermethylation was not significantly correlated to protein expression loss, which could be explained by competing mechanisms for FHIT inactivation in a substantial fraction of non FHIT hypermethylated diffuse large B-cell lymphoma. Hypermethylation was significantly associated with poor prognosis of diffuse large B-cell lymphoma patients and predominantly seen in nongerminal center diffuse large B-cell lymphoma (27%), but less frequent (13%) in germinal center diffuse large B-cell lymphoma. In summary, these data suggest that promotor hypermethylation is responsible for reduced FHIT expression in a substantial subset of diffuse large B-cell lymphoma, which is primarily composed of nongerminal center subtype with poor patient prognosis.

  18. Effects of insulin-like growth factor-1 on B-cell precursor acute lymphoblastic leukemia.

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    Yamada, Hiroyuki; Iijima, Kazutoshi; Tomita, Osamu; Taguchi, Tomoko; Miharu, Masashi; Kobayashi, Kenichiro; Okita, Hajime; Saito, Masahiro; Shimizu, Toshiaki; Kiyokawa, Nobutaka

    2013-01-01

    Insulin-like growth factor-1 (IGF-1) is known to be a major growth factor with effects on various cell types, including hematopoietic cells, as well as neoplasms, and is regulated by IGF-binding proteins (IGFBPs). In this study, we investigated the effects of IGF-1 on B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. When the expression of IGF-1R in clinical samples of BCP-ALL was examined, five of thirty-two cases showed IGF-1R expression, whereas IGF-1R was expressed in most BCP-ALL cell lines. We observed that IGF-1 enhanced the proliferation of BCP-ALL cell lines that can be partially inhibited by IGFBP-1, -3, and -4, but not other IGFBPs. IGF-1 also partially inhibited dexamethasone-induced apoptosis, but not apoptosis mediated by VP-16 and irradiation. Interestingly, the proliferative effect of IGF-1 was partially blocked by inhibitors of MAPK and AKT, whereas the inhibition of dexamethasone-induced apoptosis was completely blocked by both inhibitors. Our data indicate that IGF-1 is involved in cell proliferation and apoptosis regulation in BCP-ALL cells. Since some BCP-ALL cases express IGF-1R, it appears to be a plausible target for prognostic evaluation and may represent a new therapeutic strategy.

  19. Hemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma

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    Katherine Devitt

    2014-01-01

    Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a life-threatening clinical syndrome characterized by dysregulation of the immune system. Impaired function of cytotoxic T cells and natural killer cells is often seen, and T-cell malignancies represent most cases of lymphoma-associated HLH. HLH associated with B-cell lymphoma is rare. We describe a case of a 30-year-old man who presented with fever, splenomegaly, and hyperferritinemia. Bone marrow biopsy revealed T-cell/histiocyte-rich large B-cell lymphoma, a rare, aggressive B-cell malignancy. This case highlights the interplay between a pro-inflammatory cytokine microenvironment and tumor-mediated immune suppression, and addresses the importance of accurately diagnosing these entities for appropriate clinical management.

  20. Breast schwannoma in a patient with diffuse large B-cell lymphoma: a case report

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    Salihoglu Ayse

    2012-12-01

    Full Text Available Abstract Introduction Schwannomas are mostly benign tumors arising from Schwann cells of the nerve sheaths. Breast schwannomas are very rare and account for only 2.6% of cases. As far as we know this is the first reported case of breast schwannoma discovered in a patient with diffuse large B-cell lymphoma. The breast schwannoma was evaluated with positron emission tomography and it exhibited moderate 18F-fluorodeoxyglucose uptake. Case presentation We present the case of a breast schwannoma in a 63-year-old Caucasian woman who was diagnosed with diffuse large B-cell lymphoma. Conclusion Imaging modalities including positron emission tomography-computed tomography failed to distinguish breast schwannoma from diffuse large B-cell lymphoma involvement of the breast.

  1. Development of diffuse large B-cell lymphoma in a patient with Waldenström’s macroglobulinemia/ lymphoplasmacytic lymphoma: clonal identity between two B-cell neoplasms

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    Masayuki Shiseki

    2011-08-01

    Full Text Available Waldenström’s macroglobulinemia (WM/ lymphoplasmacytic lymphoma (LPL is an indolent mature B-cell neoplasm. In rare cases of WM/LPL, diffuse large B-cell lymphoma (DLBCL develops as a result of histologic transformation. In this report, we present a case of DLBCL developing in a patient with WM/LPL. Combination chemotherapy for DLBCL was effective and complete remission was eventually achieved. We attempted to determine the clonal relatedness between WM/LPL and DLBCL in the patient by analyzing complementarity-determining region 3 (CDR3 in the immunoglobulin heavy chain gene. A common CDR3 sequence was found in tumor cells of DLBCL and those of WM/LPL, indicating that tumor cells of DLBCL are clonally identical to those of WM/LPL. Therefore, in the present case, DLBCL is developed from WM/LPL cells by clonal evolution.

  2. Regulation of B cell linker protein transcription by PU.1 and Spi-B in murine B cell acute lymphoblastic leukemia.

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    Xu, Li S; Sokalski, Kristen M; Hotke, Kathryn; Christie, Darah A; Zarnett, Oren; Piskorz, Jan; Thillainadesan, Gobi; Torchia, Joseph; DeKoter, Rodney P

    2012-10-01

    B cell acute lymphoblastic leukemia (B-ALL) is frequently associated with mutations or chromosomal translocations of genes encoding transcription factors. Conditional deletion of genes encoding the E26-transformation-specific transcription factors, PU.1 and Spi-B, in B cells (ΔPB mice) leads to B-ALL in mice at 100% incidence rate and with a median survival of 21 wk. We hypothesized that PU.1 and Spi-B may redundantly activate transcription of genes encoding tumor suppressors in the B cell lineage. Characterization of aging ΔPB mice showed that leukemia cells expressing IL-7R were found in enlarged thymuses. IL-7R-expressing B-ALL cells grew in culture in response to IL-7 and could be maintained as cell lines. Cultured ΔPB cells expressed reduced levels of B cell linker protein (BLNK), a known tumor suppressor gene, compared with controls. The Blnk promoter contained a predicted PU.1 and/or Spi-B binding site that was required for promoter activity and occupied by PU.1 and/or Spi-B as determined by chromatin immunoprecipitation. Restoration of BLNK expression in cultured ΔPB cells opposed IL-7-dependent proliferation and induced early apoptosis. We conclude that the tumor suppressor BLNK is a target of transcriptional activation by PU.1 and Spi-B in the B cell lineage.

  3. Primary bilateral adrenal B-cell lymphoma associated with EBV and JCV infection

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    Guzzardo Vincenza

    2009-01-01

    Full Text Available Abstract Primary lymphoma of the adrenal gland is a rare and highly aggressive disease, with only a few reports in the literature. The pathogenesis is unknown, but detection of Epstein Barr virus (EBV genome sequences and gene expression in some cases of primary adrenal lymphomas suggested the virus might be a causative agent of the malignancy. While investigating the presence of genome sequences of oncogenic viruses in a large series of adrenal tumors, both EBV and JC polyomavirus (JCV DNA sequences were detected in a diffuse large primary bilateral B-cell non-Hodgkin lymphoma of the adrenal gland, which was diagnosed only at postmortem examination in a 77 year-old woman with incidentally discovered adrenal masses and primary adrenal insufficiency. The presence of both EBV and JCV genome sequences suggests the relevance of EBV and JCV coinfection in the pathogenesis of this rare form of B-cell lymphoma.

  4. B-cell Lymphoma in retrieved femoral heads: a long term follow up

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    van Kemenade Folkert J

    2009-05-01

    Full Text Available Abstract Background A relatively high incidence of pathological conditions in retrieved femoral heads, including a group of patients having low grade B-cell lymphoma, has been described before. At short term follow up none of these patients with low-grade B-cell lymphoma showed evidence of systemic disease. However, the long term follow up of these patients is not known. Methods From November 1994 up to and including December 2005 we screened all femoral heads removed at the time of primary total hip replacement histopathologically and included them in the bone banking protocol according to the guidelines of the American Associations of Tissue Banks (AATB and the European Association of Musculo-Skeletal Transplantation (EAMST. We determined the percentage of B-cell lymphoma in all femoral heads and in the group that fulfilled all criteria of the bone banking protocol and report on the long-term follow-up. Results Of 852 femoral heads fourteen (1.6% were highly suspicious for low-grade B-cell lymphoma. Of these 852 femoral heads, 504 were eligible for bone transplantation according to the guidelines of the AATB and the EAMST. Six femoral heads of this group of 504 were highly suspicious for low-grade B-cell lymphoma (1.2%. At long term follow up two (0.2% of all patients developed systemic malignant disease and one of them needed medical treatment for her condition. Conclusion In routine histopathological screening we found variable numbers of low-grade B-cell lymphoma throughout the years, even in a group of femoral heads that were eligible for bone transplantation. Allogenic transmission of malignancy has not yet been reported on, but surviving viruses are proven to be transmissible. Therefore, we recommend the routine histopathological evaluation of all femoral heads removed at primary total hip arthroplasty as a tool for quality control, whether the femoral head is used for bone banking or not.

  5. New drugs for aggressive B-cell and T-cell lymphomas.

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    Murawski, Niels; Pfreundschuh, Michael

    2010-11-01

    Over the past decade an unprecedented number of new drugs for lymphomas have been developed. Most of these new drugs target molecules or pathways that are important for the growth and proliferation of lymphomas. The introduction of the B-lymphoma specific monoclonal anti-CD20 antibody, rituximab, has improved the prognosis of patients with B-cell lymphomas more than any other drug in the past 50 years; today less than half of the patients with aggressive B-cell lymphomas die of their disease than in the pre-rituximab era. Many new drugs are now available for clinical testing in addition to new CD20 antibodies and antibodies directed against other surface molecules specifically or preferentially expressed on the lymphoma-cell surface. A prerequisite for the development of these drugs was the recognition of aberrant cell-signal transduction involved in lymphoma pathogenesis and progression. New therapeutic targets include receptor tyrosine and cyclin-dependent kinases, histone deacetylases, and molecules involved in the regulation of apoptosis. The definition of the role of these new drugs alone or in combination with established chemotherapy regimens in adequately designed prospective trials represents one of the major challenges in clinical lymphoma research.

  6. B-cell multicentric lymphoma as a probable cause of abortion in a Quarter horse broodmare.

    Science.gov (United States)

    Canisso, Igor F; Pinn, Toby L; Gerdin, Jodie A; Ollivett, Theresa L; Buckles, Elizabeth L; Schweizer, Christine M; Ainsworth, Dorothy M

    2013-03-01

    A 5-year-old Quarter horse broodmare was evaluated for inappetence, depression, and diarrhea 13 days after aborting a 9-month gestation fetus. Clinical and laboratory examination ruled out uterine rupture and peritonitis. Ultrasonography of the uterus combined with cytological analysis of peritoneal fluid suggested the existence of diffuse lymphoma. A multicentric B-cell lymphoma involving the uterus and ovary was confirmed at necropsy and histopathological examination.

  7. Primary cardiac B cell lymphoma: Manifestation of Felty's syndrome or TNFα antagonist.

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    Benzerdjeb, Nazim; Ameur, Fatima; Ikoli, Jean-Fortune; Sevestre, Henri

    2016-12-01

    Primary cardiac B cell lymphoma is rare. To date, fewer than 90 cases have been described in the literature. We report a 67-year-old woman with a 30-year history of rheumatoid arthritis, who had received treatment with leflunomide for 10 years and infliximab for 2 years. Secondary Felty's syndrome appeared. She was admitted to the hospital for abdominal pain. Investigations disclosed a 5cm cardiac mass in the right atrium. Histopathologic examination of tissue specimens obtained at surgical myocardial biopsy demonstrated primary cardiac B cell lymphoma. The other iatrogenic lymphoproliferative disorders are reviewed. This lesion might be a manifestation of long term TNFα antagonists treatment.

  8. Primary Intravascular large B-cell lymphoma of lung: a report of one case and review

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    Yu Hui

    2012-06-01

    Full Text Available Abstract Objective To investigate the clinicopathological features of primary intravascular large B-cell lymphoma of lung. Methods A case of primary pulmonary intravascular large B-cell lymphoma was analysed in histopathology and immunophenotype. Results The patient is a 42-year-old female who had cough for one year. Computed tomography showed ground-glass opacities and small nodules in bilateral lung fields. Histopathology demonstrated accumulation of similar sized neoplastic cells within alveolar capillaries, widening the alveolar septae. The alveolar structure sustained in part of districtions. Immunohistologically, the tumor cells were positive for CD20 and negative for CD3,CK, which were similar to the diffuse large B-cell lymphoma. Conclusions Intravascular large B-cell lymphoma is an uncommon type of non-Hodgkin’s lymphoma. Primary pulmonary presentation is even more rare. The diagnosis is based on the histopathology and immunohistochemistry. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2076991810705433.

  9. Diffuse large B-cell lymphoma involving the central nervous system.

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    Gualco, Gabriela; Weiss, Lawrence M; Barber, Glen N; Bacchi, Carlos E

    2011-02-01

    Lymphomas involving the central nervous system are recognized increasingly in immunocompetent as well as immunosuppressed individuals, and the majority of the cases are diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the immunophenotype, clinicopathological features, and association with Epstein-Barr virus (EBV) of DLBCL of the central nervous system (CNS) in 3 different clinical situations: primary, in immunocompetent patients; "primary," in immunosuppressed patients; and in patients with secondary involvement by systemic lymphoma. The authors reviewed the clinicopathological features, morphology, immunophenotype (according to germinal-center B-cell-like and nongerminal B-cell-like subtypes), and association with EBV in 36 cases of DLBCL of the CNS, including 25 primary cases, 5 associated with immunosuppression, and 6 cases with secondary involvement. Survival was evaluated in 15 cases of primary CNS lymphomas. Of the 36 patients, 19 were male and 18 female. Only 2 cases of lymphomas were EBV-positive; both occurred in immunosuppressed patients. Separation into germinal-center and non-germinal center subtypes by an immunohistochemistry panel showed that 68% of primary, 80% of secondary, and 83% of the cases associated with immunosuppression were of non-germinal-center subtype, respectively. Patients with non-germinal-center immunophenotype showed significantly worse survival than those with CNS lymphomas of the germinal-center subtype.

  10. Lenalidomide potentiates CD4(+)CD25(+)Treg-related suppression of lymphoma B-cell proliferation.

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    Grygorowicz, Monika Anna; Borycka, Ilona Sara; Nowak, Eliza; Paszkiewicz-Kozik, Ewa; Rymkiewicz, Grzegorz; Błachnio, Katarzyna; Biernacka, Marzena; Bujko, Mateusz; Walewski, Jan; Markowicz, Sergiusz

    2016-03-10

    We have previously found that ex vivo expanded human CD4(+)CD25(+)Treg cells suppress proliferation of lymphoma B-cell lines. Here we demonstrate that the immunomodulatory drug lenalidomide potentiates suppression of lymphoma B-cell proliferation by freshly isolated CD4(+)CD25(+)Tregs, as well as suppression by Tregs expanded polyclonally in the presence of rapamycin from CD4(+)CD25(+)T cells or CD4(+)CD25(+)CD127(lo)T cells. The regulation of lymphoma cell proliferation by Tregs pre-expanded with "third-party" allogeneic MoDCs in the presence of rapamycin was also potentiated by lenalidomide. Lenalidomide contributed to the suppression exerted by Tregs despite concomitant downregulation of Treg proliferation. Lenalidomide did not reduce the suppression of conventional T cells by expanded Tregs. The exposure of polyclonally expanded Tregs to lenalidomide did not significantly alter their phenotype. There was no uniform pattern of lenalidomide effect on Treg-mediated regulation of lymphoma B cells freshly isolated from patients. Freshly isolated lymphoma cells activated with multimeric CD40L and IL-4 to support their survival in vitro varied in their sensitivity to lenalidomide, and the regulatory effect of Tregs on such lymphoma cells ranged from suppression to help in individual patients. Lenalidomide potentiated or attenuated Treg effects on the survival of freshly isolated lymphoma cells. A combination of lenalidomide treatment with adoptive transfer of CD4(+)CD25(+)Tregs or CD4(+)CD25(+)CD127(lo)Tregs expanded ex vivo could be used to suppress proliferation of residual lymphoma in select patients with lymphoma responsive to the regulation by Tregs and sensitive to lenalidomide.

  11. A comparison between protein profiles of B cell subpopulations and mantle cell lymphoma cells

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    Lehtiö Janne

    2009-11-01

    Full Text Available Abstract Background B-cell lymphomas are thought to reflect different stages of B-cell maturation. Based on cytogenetics and molecular markers, mantle cell lymphoma (MCL is presumed to derive predominantly from naïve, pre-germinal centre (pre-GC B lymphocytes. The aim of this study was to develop a method to investigate the similarity between MCL cells and different B-cell compartments on a protein expression level. Methods Subpopulations of B cells representing the germinal centre (GC, the pre-GC mantle zone and the post-GC marginal zone were isolated from tonsils using automated magnetic cell sorting (AutoMACS of cells based on their expression of CD27 and IgD. Protein profiling of the B cell subsets, of cell lines representing different lymphomas and of primary MCL samples was performed using top-down proteomics profiling by surface-enhanced laser detection/ionization time-of-flight mass spectrometry (SELDI-TOF-MS. Results Quantitative MS data of significant protein peaks (p-value Conclusion AutoMACS sorting generates sufficient purity to enable a comparison between protein profiles of B cell subpopulations and malignant B lymphocytes applying SELDI-TOF-MS. Further validation with an increased number of patient samples and identification of differentially expressed proteins would enable a search for possible treatment targets that are expressed during the early development of MCL.

  12. Phospho-specific flow cytometry identifies aberrant signaling in indolent B-cell lymphoma

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    Blix Egil S

    2012-10-01

    Full Text Available Abstract Background Knowledge about signaling pathways in malignant cells may provide prognostic and diagnostic information in addition to identify potential molecular targets for therapy. B-cell receptor (BCR and co-receptor CD40 signaling is essential for normal B cells, and there is increasing evidence that signaling via BCR and CD40 plays an important role in the pathogenesis of B-cell lymphoma. The aim of this study was to investigate basal and induced signaling in lymphoma B cells and infiltrating T cells in single-cell suspensions of biopsies from small cell lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL and marginal zone lymphoma (MZL patients. Methods Samples from untreated SLL/CLL and MZL patients were examined for basal and activation induced signaling by phospho-specific flow cytometry. A panel of 9 stimulation conditions targeting B and T cells, including crosslinking of the B cell receptor (BCR, CD40 ligand and interleukins in combination with 12 matching phospho-protein readouts was used to study signaling. Results Malignant B cells from SLL/CLL patients had higher basal levels of phosphorylated (p-SFKs, p-PLCγ, p-ERK, p-p38, p-p65 (NF-κB, p-STAT5 and p-STAT6, compared to healthy donor B cells. In contrast, anti-BCR induced signaling was highly impaired in SLL/CLL and MZL B cells as determined by low p-SFK, p-SYK and p-PLCγ levels. Impaired anti-BCR-induced p-PLCγ was associated with reduced surface expression of IgM and CD79b. Similarly, CD40L-induced p-ERK and p-p38 were also significantly reduced in lymphoma B cells, whereas p-p65 (NF-κB was equal to that of normal B cells. In contrast, IL-2, IL-7 and IL-15 induced p-STAT5 in tumor-infiltrating T cells were not different from normal T cells. Conclusions BCR signaling and CD40L-induced p-p38 was suppressed in malignant B cells from SLL/CLL and MZL patients. Single-cell phospho-specific flow cytometry for detection of basal as well as activation

  13. Primary bilateral adrenal intravascular large B-cell lymphoma associated with adrenal failure.

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    Fukushima, Ayumi; Okada, Yosuke; Tanikawa, Takahisa; Onaka, Takashi; Tanaka, Aya; Higashi, Takehiro; Tsukada, Junichi; Tanaka, Yoshiya

    2003-07-01

    We report a rare case of bilateral primary adrenal non-Hodgkin's lymphoma with adrenal failure. A 66-year-old woman developed symptoms of adrenal failure. The cause of adrenal failure was suspected to be malignant lymphoma based on the high levels of serum soluble interleukin-2 receptor and LDH. Bilateral adrenalectomy was performed and pathological examination showed intravascular large B-cell lymphoma (IVL). Although complete remission was achieved, recurrence occurred three months later with brain metastases. IVL should be suspected in patients with bilateral adrenal tumors who present with rapidly progressive adrenal failure.

  14. Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma.

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    Muppidi, Jagan R; Schmitz, Roland; Green, Jesse A; Xiao, Wenming; Larsen, Adrien B; Braun, Sterling E; An, Jinping; Xu, Ying; Rosenwald, Andreas; Ott, German; Gascoyne, Randy D; Rimsza, Lisa M; Campo, Elias; Jaffe, Elaine S; Delabie, Jan; Smeland, Erlend B; Braziel, Rita M; Tubbs, Raymond R; Cook, J R; Weisenburger, Dennis D; Chan, Wing C; Vaidehi, Nagarajan; Staudt, Louis M; Cyster, Jason G

    2014-12-11

    Germinal centre B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common malignancy, yet the signalling pathways that are deregulated and the factors leading to its systemic dissemination are poorly defined. Work in mice showed that sphingosine-1-phosphate receptor-2 (S1PR2), a Gα12 and Gα13 coupled receptor, promotes growth regulation and local confinement of germinal centre B cells. Recent deep sequencing studies of GCB-DLBCL have revealed mutations in many genes in this cancer, including in GNA13 (encoding Gα13) and S1PR2 (refs 5,6, 7). Here we show, using in vitro and in vivo assays, that GCB-DLBCL-associated mutations occurring in S1PR2 frequently disrupt the receptor's Akt and migration inhibitory functions. Gα13-deficient mouse germinal centre B cells and human GCB-DLBCL cells were unable to suppress pAkt and migration in response to S1P, and Gα13-deficient mice developed germinal centre B-cell-derived lymphoma. Germinal centre B cells, unlike most lymphocytes, are tightly confined in lymphoid organs and do not recirculate. Remarkably, deficiency in Gα13, but not S1PR2, led to germinal centre B-cell dissemination into lymph and blood. GCB-DLBCL cell lines frequently carried mutations in the Gα13 effector ARHGEF1, and Arhgef1 deficiency also led to germinal centre B-cell dissemination. The incomplete phenocopy of Gα13- and S1PR2 deficiency led us to discover that P2RY8, an orphan receptor that is mutated in GCB-DLBCL and another germinal centre B-cell-derived malignancy, Burkitt's lymphoma, also represses germinal centre B-cell growth and promotes confinement via Gα13. These findings identify a Gα13-dependent pathway that exerts dual actions in suppressing growth and blocking dissemination of germinal centre B cells that is frequently disrupted in germinal centre B-cell-derived lymphoma.

  15. Microarray-based classification of diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Poulsen, Christian Bjørn; Borup, Rehannah; Nielsen, Finn Cilius

    2005-01-01

    OBJECTIVE: Hierarchical clusterings of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures have previously been used to classify DLBCL into Germinal Center B-cell (GCB) and Activated B-cell (ABC) types. To examine if it was feasible to perform a cross-platform validation...... was only expressed in the ABC and in Type-3 samples. The 5-year survival was similar between the groups, but GCB patients showed a better initial response to CHOP or CHOP-like regimens than the remaining patients and tended to have less advanced disease and lower IPI scores. As a next step, an improved set...

  16. Yttrium Y 90 Ibritumomab Tiuxetan, Fludarabine, Radiation Therapy, and Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

    Science.gov (United States)

    2016-03-21

    B-cell Chronic Lymphocytic Leukemia; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  17. Emerging role of infectious etiologies in the pathogenesis of marginal zone B-cell lymphomas.

    Science.gov (United States)

    Zucca, Emanuele; Bertoni, Francesco; Vannata, Barbara; Cavalli, Franco

    2014-10-15

    Extranodal marginal zone B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) arise from lymphoid populations that are induced by chronic inflammation in extranodal sites. The most frequently affected organ is the stomach, where MALT lymphoma is incontrovertibly associated with a chronic gastritis induced by a microbial pathogen, Helicobacter pylori. Gastric MALT lymphoma therefore represents a paradigm for evaluating inflammation-associated lymphomagenesis, which may lead to a deeper understanding of a possible etiologic association between other microorganisms and nongastric marginal zone lymphomas. Besides infectious etiology, chronic inflammation caused by autoimmune diseases, such as Sjögren syndrome or Hashimoto thyroiditis, can also carry a significant risk factor for the development of marginal zone lymphoma. In addition to the continuous antigenic drive, additional oncogenic events play a relevant role in lymphoma growth and progression to the point at which the lymphoproliferative process may eventually become independent of antigenic stimulation. Recent studies on MALT lymphomas have in fact demonstrated genetic alterations affecting the NF-κB) pathway, a major signaling pathway involved in many cancers. This review aims to present marginal zone lymphoma as an example of the close pathogenetic link between chronic inflammation and tumor development, with particular attention to the role of infectious agents and the integration of these observations into everyday clinical practice. See all articles in this CCR Focus section, "Paradigm Shifts in Lymphoma."

  18. Germinal center reentries of BCL2-overexpressing B cells drive follicular lymphoma progression

    Science.gov (United States)

    Sungalee, Stéphanie; Mamessier, Emilie; Morgado, Ester; Grégoire, Emilie; Brohawn, Philip Z.; Morehouse, Christopher A.; Jouve, Nathalie; Monvoisin, Céline; Menard, Cédric; Debroas, Guilhaume; Faroudi, Mustapha; Mechin, Violaine; Navarro, Jean-Marc; Drevet, Charlotte; Eberle, Franziska C.; Chasson, Lionel; Baudimont, Fannie; Mancini, Stéphane J.; Tellier, Julie; Picquenot, Jean-Michel; Kelly, Rachel; Vineis, Paolo; Ruminy, Philippe; Chetaille, Bruno; Jaffe, Elaine S.; Schiff, Claudine; Hardwigsen, Jean; Tice, David A.; Higgs, Brandon W.; Tarte, Karin; Nadel, Bertrand; Roulland, Sandrine

    2014-01-01

    It has recently been demonstrated that memory B cells can reenter and reengage germinal center (GC) reactions, opening the possibility that multi-hit lymphomagenesis gradually occurs throughout life during successive immunological challenges. Here, we investigated this scenario in follicular lymphoma (FL), an indolent GC-derived malignancy. We developed a mouse model that recapitulates the FL hallmark t(14;18) translocation, which results in constitutive activation of antiapoptotic protein B cell lymphoma 2 (BCL2) in a subset of B cells, and applied a combination of molecular and immunofluorescence approaches to track normal and t(14;18)+ memory B cells in human and BCL2-overexpressing B cells in murine lymphoid tissues. BCL2-overexpressing B cells required multiple GC transits before acquiring FL-associated developmental arrest and presenting as GC B cells with constitutive activation–induced cytidine deaminase (AID) mutator activity. Moreover, multiple reentries into the GC were necessary for the progression to advanced precursor stages of FL. Together, our results demonstrate that protracted subversion of immune dynamics contributes to early dissemination and progression of t(14;18)+ precursors and shapes the systemic presentation of FL patients. PMID:25384217

  19. Bone marrow biopsy in diffuse large B-cell lymphoma : Useful or redundant test?

    NARCIS (Netherlands)

    Adams, Hugo J A; De Klerk, John M H; Fijnheer, Rob; Heggelman, Ben G F; Dubois, Stefan V.; Nievelstein, Rutger A J; Kwee, Thomas C.

    2015-01-01

    Purpose. To determine the additional value of bone marrow biopsy (BMB) in the standard staging work-up of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), in terms of risk assessment and treatment planning. Material and methods. A total of 113 consecutive patients with newly diag

  20. Clinical Implications of Phosphorylated STAT3 Expression in De Novo Diffuse Large B-cell Lymphoma

    NARCIS (Netherlands)

    Ok, C.Y.; Chen, J.; Xu-Monette, Z.Y.; Tzankov, A.; Manyam, G.C.; Li, L.; Visco, C.; Montes-Moreno, S.; Dybkaer, K.; Chiu, A.; Orazi, A.; Zu, Y.; Bhagat, G.; Richards, K.L.; Hsi, E.D.; Choi, W.W.; Krieken, J.H.J.M. van; Huh, J.; Zhao, X.; Ponzoni, M.; Ferreri, A.J.; Bertoni, F.; Farnen, J.P.; Moller, M.B.; Piris, M.A.; Winter, J.N.; Medeiros, L.J.; Young, K.H.

    2014-01-01

    PURPOSE: Activated signal transducer and activator of transcription 3 (STAT3) regulates tumor growth, invasion, cell proliferation, angiogenesis, immune response, and survival. Data regarding expression of phosphorylated (activated) STAT3 in diffuse large B-cell lymphoma (DLBCL) and the impact of ph

  1. Cytomegalovirus enterocolitis in a patient with diffuse large B-cell lymphoma after chemotherapy with rituximab

    Institute of Scientific and Technical Information of China (English)

    Jason Seewoodhary

    2006-01-01

    Rituximab has been associated with the development of cytomegalovirus enterocolitis in immunosuppressed patients. A 51-year-old patient with diffuse large B-cell lymphoma who received a conditioning chemotherapy regimen (RCVP and RICE) consisting of rituximab before bone marrow transplantation went on to develop cytomegalovirus enterocolitis. This supports evidence from previously described cases that rituximab may be associated with cytomegalovirus enterocolitis.

  2. Clinical and pathological features of testicular diffuse large B-cell lymphoma : a heterogeneous disease

    NARCIS (Netherlands)

    Kuper-Hommel, Marion J. J.; Janssen-Heijnen, Maryska L. G.; Vreugdenhil, Gerard; Krol, Augustinus D. G.; Kluin-Nelemans, Hanneke C.; Coebergh, Jan-Willem W.; van Krieken, J. Han J. M.

    2012-01-01

    Most testicular lymphomas are of diffuse large B-cell (DLBCL) type with an outcome inferior to nodal DLBCL. Within an apparently homogeneous group of testicular DLBCLs, small cell components, plasmacytoid differentiation and lymphoepithelial lesions (LELs), features of extranodal marginal zone lymph

  3. Clonal rearrangements of immunoglobulin genes and progression to B cell lymphoma in cutaneous lymphoid hyperplasia.

    Science.gov (United States)

    Wood, G S; Ngan, B Y; Tung, R; Hoffman, T E; Abel, E A; Hoppe, R T; Warnke, R A; Cleary, M L; Sklar, J

    1989-07-01

    Cutaneous lymphoid hyperplasia (CLH) is a disorder characterized by the development of one or more skin lesions containing dense lymphoid infiltrates that exhibit the histopathologic features of a benign, reactive process. Nevertheless, some cases have been associated with the subsequent development of clinically overt lymphomas. This suggests that monoclonal populations may exist in some cases of CLH and that these cases may represent a subset more likely to evolve into lymphoma. To determine if such a subset of CLH can be distinguished, Southern blot analysis of DNA was used to study the immunogenotypic features of lesions from 14 patients with clinical, histopathologic, and immunopathologic findings characteristic of CLH. Five cases exhibited detectable clonal rearrangements of immunoglobulin genes. Furthermore, one of these five cases evolved into overt diffuse large cell lymphoma of B cell lineage during a 2-year follow-up of recurrent disease at the original cutaneous site. The immunoglobulin gene rearrangements of this lymphoma were identical to those of the prior CLH lesion. There was no evidence of detectable t(14;18) chromosomal translocations or clonal rearrangements of the beta gene of the T cell receptor in any case. It was concluded that CLH can be divided into two subsets based on the presence or absence of a clonal B cell population, and that overt lymphoma can arise from the former subset and contain the same B cell clone identified in the pre-existent CLH lesion.

  4. Lidamycin Induces Apoptosis of B-Cell Lymphoma Cells and Inhibits Xenograft Growth in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    Hong Fang; Shenghua Zhang; Qingfang Miao; Dongsheng Xiong; Yongsu Zhen

    2009-01-01

    OBJECTIVE To study the cytotoxicity of Lidamycin (LDM) and its induction of apoptosis in Raji and Daudi cells of B-cell lymphoma, and the inhibition of growth of the lymphoma Raji xenograft in nude mice.METHODS MTT assay was used to observe the inhibition by LDM on the proliferation of the Raji and Daudi cells. Annexin V-FITC/PI double-stain, in combination with flow cytometry (FCM), was used to determine the induction of apoptosis by LDM in Raji cells. The B-cell lymphoma Raji xenograft model in nude mice was set up to detect the in vivo antitumor activity of LDM.RESULTS LDM markedly inhibited the proliferation of the Raji and Daudi cells in vitro, with IC50 values of 7.13×10-11 mol/L and 2.91×10-10 mol/L, respectively. The apoptotic rates of Raji cells were respectively 77.98% and 67.63% at 0.5 nmol/L and 0.25 nmol/L of LDM, indicating an obvious induction of apoptosis in Raji cells. LDM inhibited the formation and growth of human B-cell lymphoma Raji xenograft in nude mice. The inhibition rates of tumor growth were respectively 74.9% and 65.2% in LDM at dosage group of 0.05 mg/kg and 0.025 mg/kg, suggesting an apparent prolongation of survival time in the nude mouse bearing lymphoma.CONCLUSION LDM can effectively induce apoptosis of the B-cell lymphoma cells and inhibit the xenograft growth in nude mice.

  5. EBV-positive B cell cerebral lymphoma 12 years after sex-mismatched kidney transplantation: post-transplant lymphoproliferative disorder or donor-derived lymphoma?

    LENUS (Irish Health Repository)

    Phelan, Paul J

    2010-06-01

    We present a follow-up case report of possible transmission of lymphoma 12 years after deceased-donor renal transplantation from a male donor who was found at autopsy to have had an occult lymphoma. The female recipient underwent prompt transplant nephrectomy. However, 12 years later, she presented with cerebral B cell lymphoma. A donor origin for the cerebral lymphoma was supported by in situ hybridization demonstration of a Y chromosome in the lymphoma. There was a dramatic resolution of the cerebral lesions with tapering of immunosuppression and introduction of rituximab treatment. The finding of a Y chromosome in the cerebral lymphoma does not exclude a host contribution to lymphoma development.

  6. A gene panel, including LRP12, is frequently hypermethylated in major types of B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Nicole Bethge

    Full Text Available Epigenetic modifications and DNA methylation in particular, have been recognized as important mechanisms to alter gene expression in malignant cells. Here, we identified candidate genes which were upregulated after an epigenetic treatment of B-cell lymphoma cell lines (Burkitt's lymphoma, BL; Follicular lymphoma, FL; Diffuse large B-cell lymphoma, DLBCL activated B-cell like, ABC; and germinal center like, GCB and simultaneously expressed at low levels in samples from lymphoma patients. Qualitative methylation analysis of 24 candidate genes in cell lines revealed five methylated genes (BMP7, BMPER, CDH1, DUSP4 and LRP12, which were further subjected to quantitative methylation analysis in clinical samples from 59 lymphoma patients (BL, FL, DLBCL ABC and GCB; and primary mediastinal B-cell lymphoma, PMBL. The genes LRP12 and CDH1 showed the highest methylation frequencies (94% and 92%, respectively. BMPER (58%, DUSP4 (32% and BMP7 (22%, were also frequently methylated in patient samples. Importantly, all gene promoters were unmethylated in various control samples (CD19+ peripheral blood B cells, peripheral blood mononuclear cells and tonsils as well as in follicular hyperplasia samples, underscoring a high specificity. The combination of LRP12 and CDH1 methylation could successfully discriminate between the vast majority of the lymphoma and control samples, emphasized by receiver operating characteristic analysis with a c-statistic of 0.999. These two genes represent promising epigenetic markers which may be suitable for monitoring of B-cell lymphoma.

  7. Sparganosis in a patient with diffuse large B cell lymphoma

    Directory of Open Access Journals (Sweden)

    Sang-Young Roh

    2013-01-01

    Full Text Available Sparganosis is the human infection by plerocercoid, the larvae of sparganum. Clinically, subjective symptoms do not occur in the incipient stage, but as the worm migrates, pruritus or tenderness may occur. On physical examination, soft, palpable, and sometimes migratory, subcutaneous nodules are found in sparganosis patients. As rare cases; sparganosis from the orbit, the abdominal viscera, and the breast have been reported. However, there have been no reports relating such disease to the patients′ immunocompromised status.We experienced a case of sparganosis from a patient with lymphoma whose immune system was suppressed by anticancer therapy, suggesting that the immunosuppression might affect the onset and the exacerbation of the disease. We report our case with a review of the literature.

  8. Conditional survival of patients with diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Pedersen, Niels Tinggaard; Christensen, Bjarne E

    2006-01-01

    a period of time after treatment. Conditional survival data have not been reported for lymphoma patients. METHODS: Conditional survival was estimated for 1209 patients with diffuse large B-cell lymphoma (DLBCL) from the population-based LYFO registry of the Danish Lymphoma Group. The Kaplan-Meier method...... was also significant at diagnosis, but 2 years after diagnosis only age had prognostic impact. Multivariate analysis of patients who survived > or = 3 years identified only age as a prognostic factor. CONCLUSION: For patients with DLBCL who have survived more than 1 year after diagnosis, the conditional......BACKGROUND: Prognosis of lymphoma patients is usually estimated at the time of diagnosis and the estimates are guided by the International Prognostic Index (IPI). However, conditional survival estimates are more informative clinically, as they consider those patients only who have already survived...

  9. Iodine I 131 Tositumomab and Fludarabine Phosphate in Treating Older Patients Who Are Undergoing an Autologous or Syngeneic Stem Cell Transplant for Relapsed or Refractory Non-Hodgkin's Lymphoma

    Science.gov (United States)

    2014-08-04

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  10. Generation and selection of immunized Fab phage display library against human B cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    Yongmei Shen; Xiaochun Yang; Ningzheng Dong; Xiaofang Xie; Xia Bai; Yizhen Shi

    2007-01-01

    The approval of using monoclonal antibodies as a targeted therapy in the management of patients with B cell lymphoma has led to new treatment options for this group of patients. Production of monoclonal antibodies by the traditional hybridoma technology is costly, and the resulting murine antibodies often have the disadvantage of triggering human anti-mouse antibody (HAMA) response. Therefore recombinant Fab antibodies generated by the phage display technology can be a suitable alternative in managing B cell lymphoma. In this study, we extracted total RNA from spleen cells of BALB/c mice immunized with human B lymphoma cells, and used RT-PCR to amplify cDNAs coding for the K light chains and Fd fragments of heavy chains. After appropriate restriction digests, these cDNA fragments were successively inserted into the phagemid vector pComb3H-SS to construct an immunized Fab phage display library. The diversity of the constructed library was approximately 1.94×107. Following five rounds of biopanning, soluble Fab antibodies were produced from positive clones identified by ELISA. From eight positive clones, FabC06, FabC21, FabC43 and FabC59 were selected for sequence analysis. At the level of amino acid sequences, the variable heavy domains (VH) and variable light domains (VL) were found to share 88-92% and 89-94% homology with sequences coded by the corresponding murine germline genes respectively. Furthermore, reactivity with membrane proteins of the B cell lymphoma was demonstrated by immunohistochemistry and western blotting. These immunized Fab antibodies may provide a valuable tool for further study of B cell lymphoma and could also contribute to the improvement of disease therapy.

  11. MicroRNA profiling of primary cutaneous large B-cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Lianne Koens

    Full Text Available Aberrant expression of microRNAs is widely accepted to be pathogenetically involved in nodal diffuse large B-cell lymphomas (DLBCLs. However, the microRNAs profiles of primary cutaneous large B-cell lymphomas (PCLBCLs are not yet described. Its two main subtypes, i.e., primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT and primary cutaneous follicle center lymphoma (PCFCL are characterized by an activated B-cell (ABC-genotype and a germinal center B-cell (GCB-genotype, respectively. We performed high-throughput sequencing analysis on frozen tumor biopsies from 19 cases of PCFCL and PCLBCL-LT to establish microRNA profiles. Cluster analysis of the complete microRNome could not distinguish between the two subtypes, but 16 single microRNAs were found to be differentially expressed. Single microRNA RT-qPCR was conducted on formalin-fixed paraffin-embedded tumor biopsies of 20 additional cases, confirming higher expression of miR-9-5p, miR-31-5p, miR-129-2-3p and miR-214-3p in PCFCL as compared to PCLBCL-LT. MicroRNAs previously described to be higher expressed in ABC-type as compared to GCB-type nodal DLBCL were not differentially expressed between PCFCL and PCLBCL-LT. In conclusion, PCFCL and PCLBCL-LT differ in their microRNA profiles. In contrast to their gene expression profile, they only show slight resemblance with the microRNA profiles found in GCB- and ABC-type nodal DLBCL.

  12. Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome

    Directory of Open Access Journals (Sweden)

    Vadim Gorodetskiy

    2016-01-01

    Full Text Available Sjögren’s syndrome (SS has the highest incidence of malignant lymphoproliferative disorders transformation among autoimmune diseases. We present a case of extranodal high grade lymphoma of the liver in a 52-year-old patient with long history of SS. Lymphoma manifested with sharp significant pain in the right hypochondrium, weakness, and profuse night sweats. Contrast-enhanced computed tomography scan (CT-scan of the abdomen revealed multiple low density foci with homogeneous structure and clear contours in both lobes of the liver. Histologically, proliferation of medium sized lymphoma cells with round-oval and slightly irregular nuclei with fine chromatin was shown. Immunohistochemical and molecular features of the tumors allowed diagnosis of diffuse large B-cell lymphoma (DLBCL. To exclude secondary liver lesion by non-Hodgkin lymphoma, chest and small pelvis CT-scan, endoscopy of upper and lower gastrointestinal tract and study of bone marrow were performed. After 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, the complete remission was achieved, which persists after 45 months of follow-up. Primary hepatic lymphomas are extremely rare, and previously only low-grade hepatic lymphomas have been described in SS. To our knowledge, the patient described here represents the first reported case of DLBCL with primary liver involvement in SS.

  13. Essential role of MALT1 protease activity in activated B cell-like diffuse large B-cell lymphoma.

    Science.gov (United States)

    Hailfinger, Stephan; Lenz, Georg; Ngo, Vu; Posvitz-Fejfar, Anita; Rebeaud, Fabien; Guzzardi, Montserrat; Penas, Eva-Maria Murga; Dierlamm, Judith; Chan, Wing C; Staudt, Louis M; Thome, Margot

    2009-11-24

    A key element for the development of suitable anti-cancer drugs is the identification of cancer-specific enzymatic activities that can be therapeutically targeted. Mucosa-associated lymphoid tissue transformation protein 1 (MALT1) is a proto-oncogene that contributes to tumorigenesis in diffuse large B-cell lymphoma (DLBCL) of the activated B-cell (ABC) subtype, the least curable subtype of DLBCL. Recent data suggest that MALT1 has proteolytic activity, but it is unknown whether this activity is relevant for tumor growth. Here we report that MALT1 is constitutively active in DLBCL lines of the ABC but not the GCB subtype. Inhibition of the MALT1 proteolytic activity led to reduced expression of growth factors and apoptosis inhibitors, and specifically affected the growth and survival of ABC DLBCL lines. These results demonstrate a key role for the proteolytic activity of MALT1 in DLBCL of the ABC subtype, and provide a rationale for the development of pharmacological inhibitors of MALT1 in DLBCL therapy.

  14. Primary cardiac B-cell lymphoma with atrioventricular block and paroxysmal ventricular tachycardia

    Directory of Open Access Journals (Sweden)

    Chen Ke-Wei

    2012-07-01

    Full Text Available Abstract Primary cardiac lymphoma (PCL is very rare, and is extremely challenging to diagnose due to nonspecific symptoms. When discovered, the right atrium and ventricle are most commonly affected, while diffuse cardiac involvement is uncommon. PCL is fatal unless promptly diagnosed and treated. Herein, we present the case of a 36-year-old immunocompetent male who presented with a 5-year history of non-specific chest symptoms and was diagnosed with primary diffuse cardiac large B-cell lymphoma involving the entire heart.

  15. Diffuse large B cell lymphoma presenting as a peri-anal abscess.

    Science.gov (United States)

    Jayasekera, Hasanga; Gorissen, Kym; Francis, Leo; Chow, Carina

    2014-06-04

    A non-healing peri-anal abscess can be difficult to manage and is often attributed to chronic disease. This case documents a male in his seventh decade who presented with multiple peri-anal collections. The abscess cavity had caused necrosis of the internal sphincter muscles resulting in faecal incontinence. Biopsies were conclusive for diffuse large B-cell lymphoma. A de-functioning colostomy was performed and the patient was initiated on CHOP-R chemotherapy. Anal lymphoma masquerading as a peri-anal abscess is rare. A high degree of suspicion must be maintained for an anal abscess which does not resolve with conservative management.

  16. Diffuse large B cell lymphoma presenting as a peri-anal abscess

    OpenAIRE

    Jayasekera, Hasanga; Gorissen, Kym; Francis, Leo; Chow, Carina

    2014-01-01

    A non-healing peri-anal abscess can be difficult to manage and is often attributed to chronic disease. This case documents a male in his seventh decade who presented with multiple peri-anal collections. The abscess cavity had caused necrosis of the internal sphincter muscles resulting in faecal incontinence. Biopsies were conclusive for diffuse large B-cell lymphoma. A de-functioning colostomy was performed and the patient was initiated on CHOP-R chemotherapy. Anal lymphoma masquerading as a ...

  17. Managing Patients with Cutaneous B-Cell and T-Cell Lymphomas Other Than Mycosis Fungoides.

    Science.gov (United States)

    Kheterpal, Meenal; Mehta-Shah, Neha; Virmani, Pooja; Myskowski, Patricia L; Moskowitz, Alison; Horwitz, Steven M

    2016-06-01

    Cutaneous lymphomas (CL) are a heterogeneous group of neoplasms characterized with clinical and histopathological variation, as well as overlap with benign dermatoses. Diagnosis and treatment of CLs is challenging and often requires a multidisciplinary approach. However, prognostic knowledge of these conditions and awareness of treatment options can help optimize appropriate use of available regimens, thereby improving care for patients. Here, we review the most recent literature and outline treatment themes for managing patients with cutaneous B-cell and T-cell lymphomas other than mycosis fungoides.

  18. Interim PET Scans in Diffuse Large B-Cell Lymphoma: Is It Ready for Prime Time?

    Science.gov (United States)

    Bolshinsky, Maital; Nabhan, Chadi

    2016-12-01

    Prognostication of patients with diffuse large B-cell lymphoma (DLBCL) has improved in the past decade with a variety of clinical, morphologic, molecular, and radiographic methods. Comparable to data on the value of interim positron emission tomography (I-PET) in Hodgkin lymphoma, several retrospective and prospective studies are attempting to assess the value of I-PET scanning in DLBCL patients. In this review, we briefly describe and analyze the various prognostic methods in DLBCL with specific focus on the value of I-PET scanning in this disease. This is a timely analysis, as tailoring therapies based on prognosis at diagnosis are becoming of increased investigational interest.

  19. A human follicular lymphoma B cell line hypermutates its functional immunoglobulin genes in vitro.

    Science.gov (United States)

    Wu, H; Pelkonen, E; Knuutila, S; Kaartinen, M

    1995-12-01

    The functional immunoglobulin (Ig) genes of B lymphocytes undergo somatic mutations during immune responses. These mutations modify the antigen binding site of the immunoglobulins, thereby enhancing the average affinity of the antibodies produced. The molecular mechanism underlying these B cell hypermutations remains unresolved, partly because it is difficult to grow normal B cells in long-term cell cultures and because there is no suitable transformed or malignant B cell line which generates mutations in its immunoglobulin genes in vitro. Here, we show that the recently established follicular lymphoma line HF-1.3.4 generates somatic hypermutations in vitro at a high frequency of 0.7 x 10(-6) mutations per base pair per generation in standard cell cultures (RPMI 1640 + 5% fetal calf serum). This shows for the first time that B cell hypermutation can occur without T cells or T cell factors. The mutation frequency increased approximately tenfold to 1 x 10(-5) mutations/base pair/generation with B cell-specific growth factors (interleukins-2 and -4 and three antibodies stimulatory to HF-1.3.4 cells). This HF-1.3.4 lymphoma line may help to elucidate the molecular mechanism of Ig gene hypermutation.

  20. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    Science.gov (United States)

    2014-08-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

  1. Intravascular Large B-Cell Lymphoma Presenting as Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Elham Vali Khojeini

    2014-01-01

    Full Text Available Intravascular large B-cell lymphoma (IVLBL is a rare subtype of diffuse large B-cell lymphoma that resides in the lumen of blood vessels. Patients typically present with nonspecific findings, particularly bizarre neurologic symptoms, fever, and skin lesions. A woman presented with shortness of breath and a chest CT scan showed diffuse interstitial thickening and ground glass opacities suggestive of an interstitial lung disease. On physical exam she was noted to have splenomegaly. The patient died and at autopsy was found to have an IVLBL in her lungs as well as nearly all her organs that were sampled. Although rare, IVLBL should be included in the differential diagnosis of interstitial lung disease and this case underscores the importance of the continuation of autopsies.

  2. Linear IgA dermatosis, coeliac disease, and extraintestinal B cell lymphoma.

    OpenAIRE

    Kapur, A.; Isaacs, P E; Kelsey, P R

    1995-01-01

    Linear IgA dermatosis is a malignancy associated rare bullous disorder similar to dermatitis herpetiformis. Linear IgA dermatosis differs from dermatitis herpetiformis in that the IgA deposits in the epidermal basement membrane are linear rather than granular. A patient is presented with coeliac disease who presented with linear IgA dermatosis and anaemia caused by chronic low grade B cell lymphoma.

  3. Clear cell variant of diffuse large B-cell lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Sahatciu-Meka Vjollca

    2011-05-01

    Full Text Available Abstract Introduction Diffuse large B-cell lymphoma is a diffuse proliferation of large neoplastic B lymphoid cells with a nuclear size equal to or exceeding the normal macrophage nuclei. We report a case of a clear cell variant of diffuse large B-cell lymphoma involving a lymph node in the neck, which was clinically suspected of being metastatic carcinoma. Case presentation A 39-year-old Caucasian ethnic Albanian man from Kosovo presented with a rapidly enlarging lymph node in his neck, but he also disclosed B symptoms and fatigue. A cytological aspirate of the lymph node revealed pleomorphic features. Our patient underwent a cervical lymph node biopsy (large excision. The mass was homogeneously fish-flesh, pale white tissue replacing almost the whole structure of the lymph node. The lymph node biopsy showed a partial alveolar growth pattern, which raised clinical suspicion that it was an epithelial neoplasm. With regard to morphological and phenotypic features, we discovered large nodules in diffuse areas, comprising large cells with slightly irregular nuclei and clear cytoplasm admixed with a few mononuclear cells. In these areas, there was high mitotic activity, and in some areas there were macrophages with tangible bodies. Staining for cytokeratins was negative. These areas had the following phenotypes: cluster designation marker 20 (CD20 positive, B-cell lymphoma (Bcl-2-positive, Bcl-6-, CD5-, CD3-, CD21+ (in alveolar patterns, prostate-specific antigen-negative, human melanoma black marker 45-negative, melanoma marker-negative, cytokeratin-7-negative and multiple myeloma marker 1-positive in about 30% of cells, and exhibited a high proliferation index marker (Ki-67, 80%. Conclusion According to the immunohistochemical findings, we concluded that this patient has a clear cell variant of diffuse large B-cell lymphoma of activated cell type, post-germinal center cell origin. Our patient is undergoing R-CHOP chemotherapy treatment.

  4. Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cells.

    Science.gov (United States)

    Katz, Samuel G; Labelle, James L; Meng, Hailong; Valeriano, Regina P; Fisher, Jill K; Sun, Heather; Rodig, Scott J; Kleinstein, Steven H; Walensky, Loren D

    2014-02-06

    Mantle cell lymphoma (MCL) is a highly aggressive B-cell lymphoma resistant to conventional chemotherapy. Although defined by the characteristic t(11;14) translocation, MCL has not been recapitulated in transgenic mouse models of cyclin D1 overexpression alone. Indeed, several genetic aberrations have been identified in MCL that may contribute to its pathogenesis and chemoresistance. Of particular interest is the frequent biallelic deletion of the proapoptotic BCL-2 family protein BIM. BIM exerts its pro-death function via its α-helical BH3 death domain that has the dual capacity to inhibit antiapoptotic proteins such as BCL-2 and MCL-1 and directly trigger proapoptotic proteins such as the mitochondrial executioner protein BAX. To evaluate a functional role for Bim deletion in the pathogenesis of MCL, we generated cyclin D1-transgenic mice harboring Bim-deficient B cells. In response to immunization, Eμ(CycD1)CD19(CRE)Bim(fl/fl) mice manifested selective expansion of their splenic mantle zone compartment. Three distinct immune stimulation regimens induced lymphomas with histopathologic and molecular features of human MCL in a subset of mice. Thus, deletion of Bim in B cells, in the context of cyclin D1 overexpression, disrupts a critical control point in lymphoid maturation and predisposes to the development of MCL. This genetic proof of concept for MCL pathogenesis suggests an opportunity to reactivate the death pathway by pharmacologic mimicry of proapoptotic BIM.

  5. Whole blood EBV-DNA predicts outcome in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Tisi, Maria Chiara; Cupelli, Elisa; Santangelo, Rosaria; Maiolo, Elena; Alma, Eleonora; Giachelia, Manuela; Martini, Maurizio; Bellesi, Silvia; D'Alò, Francesco; Voso, Maria Teresa; Pompili, Maurizio; Leone, Giuseppe; Larocca, Luigi Maria; Hohaus, Stefan

    2016-01-01

    An association between Epstein-Barr Virus (EBV) infection and lymphoproliferative diseases has been reported with EBV + diffuse large B cell-lymphoma (DLBCL) of the elderly described as a distinct entity. In a cohort of 218 human immunodeficiency virus (HIV)-negative patients with diffuse large B-cell lymphomas, we detected EBV-DNA in 25% of whole blood (WB) samples at diagnosis. Presence and viral load in WB, mononuclear cells or plasma did not predict the presence of EBV in the tumor biopsy. Positive Hepatitis C virus (HCV) serology was associated with a higher frequency of EBV in WB. Patients with EBV-DNA in WB had a significantly shorter progression-free (p = 0.02) and overall survival (p = 0.05) after immunochemotherapy with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone). We conclude that detection of EBV in WB is not a surrogate marker for EBV-association in diffuse large B-cell lymphoma, however it associates with worse outcome.

  6. G-rich proto-oncogenes are targeted for genomic instability in B-cell lymphomas.

    Science.gov (United States)

    Duquette, Michelle L; Huber, Michael D; Maizels, Nancy

    2007-03-15

    Diffuse large B-cell lymphoma is the most common lymphoid malignancy in adults. It is a heterogeneous disease with variability in outcome. Genomic instability of a subset of proto-oncogenes, including c-MYC, BCL6, RhoH, PIM1, and PAX5, can contribute to initial tumor development and has been correlated with poor prognosis and aggressive tumor growth. Lymphomas in which these proto-oncogenes are unstable derive from germinal center B cells that express activation-induced deaminase (AID), the B-cell-specific factor that deaminates DNA to initiate immunoglobulin gene diversification. Proto-oncogene instability is evident as both aberrant hypermutation and translocation, paralleling programmed instability which diversifies the immunoglobulin loci. We have asked if genomic sequence correlates with instability in AID-positive B-cell lymphomas. We show that instability does not correlate with enrichment of the WRC sequence motif that is the consensus for deamination by AID. Instability does correlate with G-richness, evident as multiple runs of the base guanine on the nontemplate DNA strand. Extending previous analysis of c-MYC, we show experimentally that transcription of BCL6 and RhoH induces formation of structures, G-loops, which contain single-stranded regions targeted by AID. We further show that G-richness does not characterize translocation breakpoints in AID-negative B- and T-cell malignancies. These results identify G-richness as one feature of genomic structure that can contribute to genomic instability in AID-positive B-cell malignancies.

  7. Endoscopic biopsy of a B-cell lymphoma involving the entire ventricular system: A case report

    Science.gov (United States)

    QIN, JIA-ZHEN; WU, YUE-KUI; YANG, ZHI-JUN; LV, JUN; DANG, YUAN-YUAN; ZHANG, HONG-TIAN; DAI, YI-WU

    2016-01-01

    A 62-year-old male suffering from vomiting and mild preceding nausea for 15 days was examined in the present case report. Magnetic resonance imaging revealed a homogeneously enhancing cluster-like lesion involving the lateral, third and fourth ventricles. An endoscopic biopsy was performed, and histopathological examination led to the diagnosis of a high-grade diffuse large B-cell lymphoma. To the best of our knowledge, the present study reports the first case of a primary lymphoma involving the entire ventricular system. Therefore, primary lymphomas should be considered in the list of ventricular tumors. An endoscopic biopsy requires minimal invasion to obtain an adequate tissue sample, and frequently leads to the correct diagnosis and subsequent treatment protocols. PMID:26889262

  8. Aberrant Circulating Th17 Cells in Patients with B-Cell Non-Hodgkin's Lymphoma.

    Science.gov (United States)

    Lu, Ting; Yu, Shuang; Liu, Yan; Yin, Congcong; Ye, Jingjing; Liu, Zhi; Ma, Daoxin; Ji, Chunyan

    2016-01-01

    Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of neoplasm in which 90% are B-cell lymphomas and 10% T-cell lymphomas. Although T-helper 17 (Th17) cells have been implicated to be essential in the pathogenesis of autoimmune and inflammatory diseases, its role in B-cell non-Hodgkin's lymphoma (B-NHL) remains unknown. In this study, we observed a significantly decreased frequency of Th17 cells in peripheral blood from B-NHL patients compared with healthy individuals, accompanied with increased Th1 cells. IL-17AF plasma levels were remarkably decreased in B-NHL patients, accompanied with undetectable IL-17FF and unchangeable IL-17AA. Moreover, Th17 and Th1 cells became normalized after one or two cycles of chemotherapy. Interestingly, in B-NHL, circulating Th17 cells frequencies were significantly higher in relapsed patients than those in untreated patients or normal individuals. Meanwhile, there was no statistical difference regarding the frequencies of Th1 cells between relapsed and untreated patients. Taken these data together, circulating Th17 subset immune response may be associated with the response of patients to treatment and with different stages of disease.

  9. FAU in Treating Patients With Advanced Solid Tumors or Lymphoma

    Science.gov (United States)

    2014-01-06

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell

  10. Clinical significance of bcl-2 protein expression and classification algorithm in diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    李敏

    2013-01-01

    Objective To investigate the clinical significance of bcl-2 protein expression and three classification algorithms including Hans model,Chan model and Muris model in patients with diffuse large B-cell lymphoma(DLBCL).

  11. Generation of cytotoxic T lymphocytes specific for B-cell acute lymphoblastic leukemia family-shared peptides derived from immunoglobulin heavy chain framework region

    Institute of Scientific and Technical Information of China (English)

    LIU Ying; ZHU Ping; HU Ya-mei

    2007-01-01

    Background Immunoglobulin heavy chain variable region (IgHV) is a well-characterized tumor antigen for B-cell malignancies. It can function as a target for T cell-mediated immune response. Clinical trials of IgHV protein vaccines against lymphoma have demonstrated induction of tumor-specific cytotoxic T lymphocyte (CTL) responses. However,complementary determining regions-based individual vaccines have disadvantages for wide clinical application. Although a recent study demonstrated that immunogenic peptides are derived from framework regions (FR) shared among patients with B-cell lymphoma, how to choose the appropriate peptides for each patient is still unsolved. The aim of this study was to investigate whether immunoglobulin heavy chain FR-derived peptides shared in each IgHV family are potential CTL epitopes presented by B-cell acute lymphoblastic leukemia (B-ALL). Such CTL epitopes might be beneficial to shifting vaccination strategies against B-ALL from individual specificity to family specificity.Methods Seven IgHV gene families were amplified respectively by PCR and sequenced directly from 71 childhood B-ALL cases. Bioinformatics was applied in analyzing characteristics of sequences available and predicting HLA-A*0201-restricted CTL epitopes for each IgHV family. An antigen-specific T cell expansion system was used to generate peptide-specific CTLs. The cytotoxicity of CTLs against B-ALL cells was assessed in the lactate dehydrogenase release assay.Results Complete IgHV rearrangements were identified in all of the 71 B-ALL cases. All of 40 sequences available showed ≥98% homology with the nearest germline IgHV genes, indicating IgHV genes in B-ALL of germline nature.Twelve nonapeptides of high HLA-A*0201-binding scores were obtained from 26 productive IgHV protein sequences. Ten (83%) of the peptides were located in FR1 and FR3 shared among the corresponding IgHV family. CTLs specific for the peptide QLVQSGAEV located in FR1 (3-11) shared among the IgHV1

  12. Absence of missense mutations in activated c-myc genes in avian leukosis virus-induced B-cell lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, M.; Hayward, W.S.

    1988-06-01

    The authors determined the nucleotide sequences of two independent DNA clones which contained the activated c-myc genes from avian leukosis virus-induced B-cell lymphomas. Neither of these c-myce genes contained missense mutations. This strongly supports the notion that the c-myc photo-oncogene in avian leukosis virus-induced B-cell lymphomas can be oncogenically activated by altered expression of the gene without a change in the primary structure of the gene product.

  13. Rapid progression of mediastinal tumor within a few days: A case report of T cell lymphoblastic lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Tae Ran; Lee, Young Kyung; Jun, Hyun Jung; Jung, Eun Ah; Son, Jin Sung [Seoul Medical Center, Seoul (Korea, Republic of)

    2016-05-15

    T-cell lymphoblastic lymphoma is a highly aggressive tumor derived from lymphocyte of the thymus, which accounts for 2% of non-Hodgkin's lymphoma. The disease occurs most commonly in adolescent and young adult males. It often results in respiratory emergency because of high proliferation rate. In this case, we confirmed the rapid progression of T-cell lymphoblastic lymphoma through the chest CT scan with one week interval. Three days of empirical chemotherapy resulted in substantial reduction of mediastinal mass, pleural thickening and pleural effusion.

  14. Genetically Modified T-cell Infusion Following Peripheral Blood Stem Cell Transplant in Treating Patients With Recurrent or High-Risk Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-01-27

    Adult Grade III Lymphomatoid Granulomatosis; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  15. Induction of B-cell lymphoma by UVB Radiation in p53 Haploinsufficient Mice

    Directory of Open Access Journals (Sweden)

    Ullrich Stephen E

    2011-01-01

    Full Text Available Abstract Background The incidence of non-Hodgkin's lymphoma has increased over recent years. The exact etiology of lymphoma remains unknown. Ultraviolet light exposure has been associated with the development of internal lymphoid malignancies and some reports suggest that it may play a role in the development of lymphoma in humans. Here we describe the characterization and progression of lymphoma in p53 heterozygous mice exposed to UVB irradiation. Methods UVB-irradiated p53+/- mice developed enlargement of the spleen. Isolated spleen cells were transplanted into Rag deficient hosts. The UV-induced tumor cells were analyzed by flow cytometry. The tumor cells were tagged with GFP to study their metastatic potential. SKY and karyotypic analysis were carried out for the detection of chromosomal abnormalities. Functional assays included in vitro class switch recombination assay, immunoglobulin rearrangement assay, as well as cytokine profiling. Results UVB-exposed mice showed enlargement of the spleen and lymph nodes. Cells transplanted into Rag deficient mice developed aggressive tumors that infiltrated the lymph nodes, the spleen and the bone marrow. The tumor cells did not grow in immune competent syngeneic C57Bl/6 mice yet showed a modest growth in UV-irradiated B6 mice. Phenotypic analysis of these tumor cells revealed these cells are positive for B cell markers CD19+, CD5+, B220+, IgM+ and negative for T cell, NK or dendritic cell markers. The UV-induced tumor cells underwent robust in vitro immunoglobulin class switch recombination in response to lipopolysaccharide. Cytogenetic analysis revealed a t(14;19 translocation and trisomy of chromosome 6. These tumor cells secret IL-10, which can promote tumor growth and cause systemic immunosuppression. Conclusion UV-irradiated p53+/- mice developed lymphoid tumors that corresponded to a mature B cell lymphoma. Our results suggest that an indirect mechanism is involved in the development of internal

  16. UCH-L1 is induced in germinal center B cells and identifies patients with aggressive germinal center diffuse large B-cell lymphoma.

    Science.gov (United States)

    Bedekovics, Tibor; Hussain, Sajjad; Feldman, Andrew L; Galardy, Paul J

    2016-03-24

    Gene expression profiling has identified 2 major subclasses of diffuse large B-cell lymphoma (DLBCL). Cases resembling germinal center (GC) B cells (GCB-DLBCL) generally occur in younger patients, have a distinct molecular pathophysiology, and have improved outcomes compared with those similar to activated post-GC cells (activated B-cell DLBCL). We previously found that the ubiquitin hydrolase UCH-L1 is frequently overexpressed in mature B-cell malignancies and is a potent oncogene in mice. The cause for its overexpression in lymphoma, and whether it impacts the outcome of patients with DLBCL is unknown. Here, we show that UCH-L1 reflects GC lineage in lymphoma and is an oncogenic biomarker of aggressive GCB-DLBCL. We find that UCH-L1 is specifically induced in GC B cells in mice and humans, and that its expression correlates highly with the GCB subtype in DLBCL. We also find that UCH-L1 cooperates with BCL6 in a mouse model of GC B-cell lymphoma, but not with the development of multiple myeloma derived from post-GC cells. Despite the typically good outcomes of GCB-DLBCL, increased UCHL1 identifies a subgroup with early relapses independent of MYC expression, suggesting biological diversity in this subset of disease. Consistent with this, forced Uchl1 overexpression had a substantial impact on gene expression in GC B cells including pathways of cell cycle progression, cell death and proliferation, and DNA replication. These data demonstrate a novel role for UCH-L1 outside of the nervous system and suggest its potential use as a biomarker and therapeutic target in DLBCL.

  17. Stereotyped patterns of B-cell receptor in splenic marginal zone lymphoma

    KAUST Repository

    Zibellini, S.

    2010-05-29

    Antigen stimulation may be important for splenic marginal zone lymphoma pathogenesis. To address this hypothesis, the occurrence of stereotyped B-cell receptors was investigated in 133 SMZL (26 HCV+) compared with 4,414 HCDR3 sequences from public databases. Sixteen SMZL (12%) showed stereotyped BCR; 7 of 86 (8%) SMZL sequences retrieved from public databases also belonged to stereotyped HCDR3 subsets. Three categories of subsets were identified: i) SMZL-specific subsets (n=5), composed only of 12 SMZL (9 HCV- from our series); ii) Non-Hodgkin\\'s lymphoma-like subsets (n=5), comprising 5 SMZL (4 from our series) clustering with other indolent lymphomas; iii) "CLL-like subsets" (n=6), comprising 6 SMZL (3 from our series) that belonged to known CLL subsets (n=4) or clustered with public CLL sequences. Immunoglobulin 3D modeling of 3 subsets revealed similarities in antigen binding regions not limited to HCDR3. Overall, data suggest that the pathogenesis of splenic marginal zone lymphoma may involve also HCV unrelated epitopes or an antigenic trigger common to other indolent lymphomas. ©2010 Ferrata Storti Foundation.

  18. Diffuse large B-cell lymphoma arising from a multicentric mixed variant of Castleman′s disease

    Directory of Open Access Journals (Sweden)

    Venizelos I

    2004-01-01

    Full Text Available This case report describes a patient with multicentric mixed type Castleman′s disease and concomitant non-Hodgkin′s lymphoma of diffuse large B cell type in the neck. Multicentric CD is a systemic illness with disseminated lymphadenopathy; its aggressive and usually fatal course is associated with infectious complications and risk for malignant tumors, such as lymphoma or Kaposi sarcoma.

  19. FOXP1 suppresses immune response signatures and MHC class II expression in activated B-cell-like diffuse large B-cell lymphomas

    DEFF Research Database (Denmark)

    Brown, P J; Wong, K K; Felce, S L;

    2016-01-01

    The FOXP1 (forkhead box P1) transcription factor is a marker of poor prognosis in diffuse large B-cell lymphoma (DLBCL). Here microarray analysis of FOXP1-silenced DLBCL cell lines identified differential regulation of immune response signatures and major histocompatibility complex class II (MHC ...

  20. Sleeping Beauty transposon screen identifies signaling modules that cooperate with STAT5 activation to induce B cell acute lymphoblastic leukemia

    Science.gov (United States)

    Heltemes-Harris, Lynn M.; Larson, Jon D.; Starr, Timothy K.; Hubbard, Gregory K.; Sarver, Aaron L.; Largaespada, David A.; Farrar, Michael A.

    2015-01-01

    STAT5 activation occurs frequently in human progenitor B cell acute lymphoblastic leukemia (B-ALL). To identify gene alterations that cooperate with STAT5 activation to initiate leukemia we crossed mice expressing a constitutively active form of STAT5 (Stat5b-CA) to mice in which a mutagenic Sleeping Beauty transposon (T2/Onc) was mobilized only in B cells. Stat5b-CA mice typically do not develop B-ALL (<2% penetrance); in contrast, 89% of Stat5b–CA mice in which the T2/Onc transposon had been mobilized died of B-ALL by 3 months of age. High-throughput sequencing approaches were used to identify genes frequently targeted by the T2/Onc transposon; these included Sos1 (74%), Kdm2a (35%), Jak1 (26%), Bmi1 (19%), Prdm14 or Ncoa2 (13%), Cdkn2a (10%), Ikzf1 (8%), Caap1 (6%) and Klf3 (6%). Collectively, these mutations target three major cellular processes: (i) the JAK/STAT5 pathway (ii) progenitor B cell differentiation and (iii) the CDKN2A tumor suppressor pathway. Transposon insertions typically resulted in altered expression of these genes, as well as downstream pathways including STAT5, ERK and p38. Importantly, expression of Sos1 and Kdm2a, and activation of p38, correlated with survival, further underscoring the role these genes and associated pathways play in B-ALL. PMID:26500062

  1. Ibrutinib inhibits pre-BCR(+) B-cell acute lymphoblastic leukemia progression by targeting BTK and BLK.

    Science.gov (United States)

    Kim, Ekaterina; Hurtz, Christian; Koehrer, Stefan; Wang, Zhiqiang; Balasubramanian, Sriram; Chang, Betty Y; Müschen, Markus; Davis, R Eric; Burger, Jan A

    2017-03-02

    Targeting B-cell receptor (BCR) signaling is a successful therapeutic strategy in mature B-cell malignancies. Precursor BCR (pre-BCR) signaling, which is critical during normal B lymphopoiesis, also plays an important role in pre-BCR(+) B cell acute lymphoblastic leukemia (B-ALL). Here, we investigated the activity and mechanism of action of the BTK inhibitor ibrutinib in preclinical models of B-ALL. Pre-BCR(+) ALL cells were exquisitely sensitive to ibrutinib at therapeutically relevant drug concentrations. In pre-BCR(+) ALL, ibrutinib thwarted autonomous and induced pre-BCR signaling, resulting in deactivation of PI3K/Akt signaling. Ibrutinib modulated the expression of pre-BCR regulators (PTPN6, CD22, CD72, and PKCβ) and substantially reduced BCL6 levels. Ibrutinib inhibited ALL cell migration toward CXCL12 and beneath marrow stromal cells and reduced CD44 expression. CRISPR-Cas9 gene editing revealed that both BTK and B lymphocyte kinase (BLK) are relevant targets of ibrutinib in pre-BCR(+) ALL. Consequently, in mouse xenograft models of pre-BCR(+) ALL, ibrutinib treatment significantly prolonged survival. Combination treatment of ibrutinib with dexamethasone or vincristine demonstrated synergistic activity against pre-BCR(+) ALL. These data corroborate ibrutinib as a promising targeted agent for pre-BCR(+) ALL and highlight the importance of ibrutinib effects on alternative kinase targets.

  2. Mosaic Down syndrome and acute lymphoblastic B cell-leukemia. Case report

    Directory of Open Access Journals (Sweden)

    Parra-Baltazar, Isabel Mónica

    2016-10-01

    Full Text Available Down syndrome (DS or trisomy 21 is a constitutional chromosomal abnormality, which may be mosaic in 1 % to 4 % of cases. DS mosaic diagnosis is difficult because most patients have a normal phenotype and show no significant clinical abnormalities. Patients with DS have a higher risk of developing acute leukemia such as acute lymphoblastic leukemia (ALL. We report the case of a 19-year old woman with mosaic trisomy 21 and ALL.

  3. Nanoparticle-based strategy for personalized B-cell lymphoma therapy

    Directory of Open Access Journals (Sweden)

    Martucci NM

    2016-11-01

    Full Text Available Nicola M Martucci,1,* Nunzia Migliaccio,1,* Immacolata Ruggiero,1,* Francesco Albano,2 Gaetano Calì,3 Simona Romano,1 Monica Terracciano,4 Ilaria Rea,4 Paolo Arcari,1 Annalisa Lamberti1 1Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples, 2Department of Experimental and Clinical Medicine, University of Catanzaro “Magna Graecia”, Catanzaro, 3Institute of Endocrinology and Molecular Oncology, 4Institute for Microelectronics and Microsystems, National Research Council, Naples, Italy *These authors contributed equally to this work Abstract: B-cell lymphoma is associated with incomplete response to treatment, and the development of effective strategies targeting this disease remains challenging. A new personalized B-cell lymphoma therapy, based on a site-specific receptor-mediated drug delivery system, was developed in this study. Specifically, natural silica-based nanoparticles (diatomite were modified to actively target the antiapoptotic factor B-cell lymphoma/leukemia 2 (Bcl2 with small interfering RNA (siRNA. An idiotype-specific peptide (Id-peptide specifically recognized by the hypervariable region of surface immunoglobulin B-cell receptor was exploited as a homing device to ensure specific targeting of lymphoma cells. Specific nanoparticle uptake, driven by the Id-peptide, was evaluated by flow cytometry and confocal microscopy and was increased by approximately threefold in target cells compared with nonspecific myeloma cells and when a random control peptide was used instead of Id-peptide. The specific internalization efficiency was increased by fourfold when siRNA was also added to the modified nanoparticles. The modified diatomite particles were not cytotoxic and their effectiveness in downregulation of gene expression was explored using siRNA targeting Bcl2 and evaluated by quantitative real-time polymerase chain reaction and Western blot analyses. The resulting gene silencing

  4. B-cell and T-cell lymphomas of the breast: clinical--pathological features of 53 cases.

    Science.gov (United States)

    Gualco, Gabriela; Bacchi, Carlos E

    2008-10-01

    Breast involvement by non-Hodgkin lymphomas is rare. We studied the morphological, immunophenotypical, and clinical features of 53 cases of malignant lymphomas involving the breast in a population of Brazilian patients. Most of the cases were of B-cell phenotype. Four of the patients with primary breast lymphomas had T-cell lymphomas, 3 had CD30-positive anaplastic large cell lymphomas, and 1 had panniculitis-like T-cell lymphoma. Most patients presented with an incidental breast mass. Secondary breast lymphoma was seen in 19 patients and most commonly occurred as part of widespread nodal disease. Two patients presented with bilateral breast involvement. The most prevalent histological subtype was also diffuse large B-cell lymphoma, followed by follicular lymphoma. This study shows that the broad morphological and immunophenotypical spectrum of malignant lymphoma of the breast occurring in a large series of Brazilian patients has many similarities with that seen in Western countries, with a higher proportion of high-grade lymphomas in both primary and secondary cases.

  5. [MALT B cell lymphoma with kidney damage and monoclonal gammopathy: a case study and literature review].

    Science.gov (United States)

    Peces, R; Vega-Cabrera, C; Peces, C; Pobes, A; Fresno, M F

    2010-01-01

    We report a case of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) involving the left kidney and simultaneous onset of a monoclonal gammopathy IgM kappa. No predisposing local inflammatory condition was identified. Following left nephrectomy, the renal specimen showed the centrocyte like cells and lymphoid cells in the lymphoepithelial lesions were positive for CD20 and CD79α. The neoplastic cells expressed monotypic cytoplasmic IgM kappa. The demonstration of bone marrow cells of B-lineage expressing the same monoclonal protein as the tumor suggested bone marrow involvement, even in the absence of identical morphology. Despite chemotherapy and rituximab treatment, clinical follow-up showed right kidney extension with high-grade transformation, and finally systemic dissemination. This case illustrates that the kidney is among the sites that may be involved by MALT B-cell lymphomas in a primary or secondary fashion, and the need for expanded investigation of the possible dissemination. We review the literature on this unusual extranodal lymphoma.

  6. The Role of mTOR Inhibitors for the Treatment of B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Pinelopi Argyriou

    2012-01-01

    Full Text Available Despite the fact that the majority of lymphomas initially respond to treatment, many patients relapse and die from disease that is refractory to current regimens. The need for new treatment strategies in lymphomas has led to the investigation and evaluation of novel agents that target cellular pathways. The mammalian target of rapamycin (mTOR is a representative pathway that may be implicated in lymphomagenesis. Rapamycin and especially its derivatives (temsirolimus, everolimus, and deforolimus represent the first described mTOR inhibitors. These agents have shown promising results in the treatment of lymphoid malignancies. On the other hand, new ATP-competitive mTOR inhibitors that provoke a broader inhibition of mTOR activity are in early stages of clinical development. The purpose of this paper is to summarize the existing knowledge about mTOR inhibitors and their use in the treatment of B-cell lymphomas. Relevant issues regarding mTOR biology in general as well as in B-cell lymphoid neoplasms are also discussed in short.

  7. Novel murine B-cell lymphoma/leukemia model to study BCL2-driven oncogenesis.

    Science.gov (United States)

    Meijerink, Jules P P; Van Lieshout, Esther M M; Beverloo, H Berna; Van Drunen, Ellen; Mensink, Ewald J B M; Macville, Merryn; Pieters, Rob

    2005-05-10

    The BCL-2 family has been implicated in the pathogenesis of various hematopoietic malignancies, including follicular non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia. To identify genes that act synergistically in BCL2-enforced leukemogenesis, we developed a murine B-cell lymphoma/leukemia model based on the IL-3-dependent Balb/C pro-B line (FL5.12). FL5.12 cells were stably transfected with antiapoptotic BCL-2 alone or in combination with proapoptotic BAX or nonfunctional mutant BAX, thereby creating various levels of imbalance within the BCL-2 family. Transfectants were intravenously injected into normal Balb/C mice. Whereas FL5.12 cells did not provoke leukemia, mice injected with stable transfectants died of leukemia over time. Disease incidence and latency time depended on the degree of imbalance in the BCL-2 family, supporting a model whereby BCL2 drives tumorigenesis. All mice presented with hepatosplenomegaly and leukemic FL5.12 cells in peripheral blood and bone marrow compartments. Leukemic conversion was accompanied by secondary genetic aberrations leading to clonal IL-3-responsive leukemia. Cellular transformation was independent of alterations in c-Myc or downstream apoptotic pathway. Leukemic clones retained a normal DNA damage response leading to elevated P53 and P21 levels and cell cycle arrest upon irradiation. In conclusion, our mouse model may prove a valuable tool to identify genes that cooperate in BCL2-enforced lymphoma/leukemogenesis.

  8. Dose Monitoring of Busulfan and Combination Chemotherapy in Hodgkin or Non-Hodgkin Lymphoma Undergoing Stem Cell Transplant

    Science.gov (United States)

    2015-08-12

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult

  9. Burkitt's lymphoma is a malignancy of mature B cells expressing somatically mutated V region genes.

    Science.gov (United States)

    Klein, U.; Klein, G.; Ehlin-Henriksson, B.; Rajewsky, K.; Küppers, R.

    1995-01-01

    BACKGROUND: The developmental stage from which stems the malignant B cell population in Burkitt's lymphoma (BL) is unclear. An approach to answering this question is provided by the sequence analysis of rear-ranged immunoglobulin (Ig) variable region (V) genes from BL for evidence of somatic mutations, together with a phenotypic characterization. As somatic hypermutation of Ig V region genes occurs in germinal center B cells, somatically mutated Ig genes are found in germinal center B cells and their descendents. MATERIALS AND METHODS: Rearranged V kappa region genes from 10 kappa-expressing sporadic and endemic BL-derived cell lines (9 IgM and 1 IgG positive) and three kappa-expressing endemic BL biopsy specimens were amplified by polymerase chain reaction and sequenced. In addition, VH region gene sequences from these cell lines were determined. RESULTS: All BL cell lines and the three biopsy specimens carried somatically mutated V region genes. The average mutation frequency of rearranged V kappa genes from eight BL cell lines established from sporadic BL was 1.8%. A higher frequency (6%) was found in five endemic cases (three biopsy specimens and two BL cell lines). CONCLUSIONS: The detection of somatic mutations in the rearranged V region genes suggests that both sporadic and endemic BL represent a B-cell malignancy originating from germinal center B cells or their descendants. Interestingly, the mutation frequency detected in sporadic BL is in a range similar to that characteristic for IgM-expressing B cells in the human peripheral blood and for mu chain-expressing germinal center B cells, whereas the mutation frequency found in endemic BL is significantly higher. PMID:8529116

  10. High sensitivity of flow cytometry improves detection of occult leptomeningeal disease in acute lymphoblastic leukemia and lymphoblastic lymphoma.

    Science.gov (United States)

    Del Principe, Maria Ilaria; Buccisano, Francesco; Cefalo, Mariagiovanna; Maurillo, Luca; Di Caprio, Luigi; Di Piazza, Fabio; Sarlo, Chiara; De Angelis, Gottardo; Irno Consalvo, Maria; Fraboni, Daniela; De Santis, Giovanna; Ditto, Concetta; Postorino, Massimiliano; Sconocchia, Giuseppe; Del Poeta, Giovanni; Amadori, Sergio; Venditti, Adriano

    2014-09-01

    Conventional cytology (CC) of cerebrospinal fluid (CSF) fails to demonstrate malignant cells in up to 45 % of patients with acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LL) in whom occult leptomeningeal disease is present. Flow cytometry (FCM) is considered more sensitive than CC, but clinical implications of CC negativity/CC positivity are not yet established. CSF samples from 38 adult patients with newly diagnosed ALL/LL were examined. Five (13 %) and nine (24 %) specimens were CC positive-FC positive (FCM(pos)/CC(pos)) and CC negative-FC positive (CC(neg)/FCM(pos)), respectively. The remaining 24 (63 %) samples were double negative (CC(neg)/FCM(neg)) (p = 0.001). CC(neg)/FCM(pos) patients showed a significantly shorter overall survival (OS) compared to CC(neg)/FCM(neg) ones. In multivariate analysis, the status of single FCM positivity was demonstrated to affect independently duration of OS (p = 0.005). In conclusion, FCM significantly improves detection of leptomeningeal occult localization in ALL/LL and appears to anticipate an adverse outcome. Further prospective studies on larger series are needed to confirm this preliminary observation.

  11. Massive transcriptional perturbation in subgroups of diffuse large B-cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Maciej Rosolowski

    Full Text Available Based on the assumption that molecular mechanisms involved in cancerogenesis are characterized by groups of coordinately expressed genes, we developed and validated a novel method for analyzing transcriptional data called Correlated Gene Set Analysis (CGSA. Using 50 extracted gene sets we identified three different profiles of tumors in a cohort of 364 Diffuse large B-cell (DLBCL and related mature aggressive B-cell lymphomas other than Burkitt lymphoma. The first profile had high level of expression of genes related to proliferation whereas the second profile exhibited a stromal and immune response phenotype. These two profiles were characterized by a large scale gene activation affecting genes which were recently shown to be epigenetically regulated, and which were enriched in oxidative phosphorylation, energy metabolism and nucleoside biosynthesis. The third and novel profile showed only low global gene activation similar to that found in normal B cells but not cell lines. Our study indicates novel levels of complexity of DLBCL with low or high large scale gene activation related to metabolism and biosynthesis and, within the group of highly activated DLBCLs, differential behavior leading to either a proliferative or a stromal and immune response phenotype.

  12. Cyclin D1 (Bcl-1, PRAD1) protein expression in low-grade B-cell lymphomas and reactive hyperplasia.

    OpenAIRE

    Yang, W. I.; Zukerberg, L R; Motokura, T.; Arnold, A.; Harris, N. L.

    1994-01-01

    Mantle cell (centrocytic) lymphoma (MCL) and occasional cases of B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia (B-SLL/CLL) show a characteristic translocation, t(11:14)(q13;q32) involving rearrangement of the Bcl-1 region. Recently it was shown that the key Bcl-1 region oncogene is cyclin D1/PRAD1; cyclin D1 mRNA was shown to be overexpressed in cases of MCL. We examined cyclin D1 protein expression in low-grade B-cell lymphomas and reactive lymphoid hyperplasias using polycl...

  13. Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma

    Science.gov (United States)

    2016-04-25

    Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  14. EBV-positive diffuse large B-cell lymphoma of the elderly is an aggressive post-germinal center B-cell neoplasm characterized by prominent nuclear factor-kB activation.

    Science.gov (United States)

    Montes-Moreno, Santiago; Odqvist, Lina; Diaz-Perez, Julio A; Lopez, Ana Batlle; de Villambrosía, Sonia Gonzalez; Mazorra, Francisco; Castillo, Maria E; Lopez, Mar; Pajares, Raquel; García, Juan F; Mollejo, Manuela; Camacho, Francisca I; Ruiz-Marcellán, Carmen; Adrados, Magdalena; Ortiz, Nazario; Franco, Renato; Ortiz-Hidalgo, Carlos; Suarez-Gauthier, Ana; Young, Ken H; Piris, Miguel A

    2012-07-01

    Here, we report a retrospective series of 47 EBV-positive diffuse large B-cell lymphoma associated with advanced age. Histopathology allowed to the identification of different histological patterns: cases with polymorphic diffuse large B-cell lymphoma (29 cases), Hodgkin-like (8 cases) and polymorphic lymphoproliferative disorder-like (9 cases) patterns. One case was purely monomorphic diffuse large B-cell lymphoma. We show that this lymphoma type is a neoplasm with prominent classical and alternative nuclear factor-kB pathway activation in neoplastic cells (79% of the cases showed nuclear staining for p105/p50, 74% for p100/p52 and 63% for both proteins), with higher frequency than that observed in a control series of EBV-negative diffuse large B-cell lymphoma (χ(2) positive diffuse large B-cell lymphoma of the elderly.

  15. Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma.

    Directory of Open Access Journals (Sweden)

    Bonnie K Harrington

    Full Text Available Acalabrutinib (ACP-196 is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL. First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Acalabrutinib also inhibited proliferation in CLBL1 cells. Twenty dogs were enrolled in the clinical trial and treated with acalabrutinib at dosages of 2.5 to 20mg/kg every 12 or 24 hours. Acalabrutinib was generally well tolerated, with adverse events consisting primarily of grade 1 or 2 anorexia, weight loss, vomiting, diarrhea and lethargy. Overall response rate (ORR was 25% (5/20 with a median progression free survival (PFS of 22.5 days. Clinical benefit was observed in 30% (6/20 of dogs. These findings suggest that acalabrutinib is safe and exhibits activity in canine B-cell lymphoma patients and support the use of canine lymphoma as a relevant model for human non-Hodgkin lymphoma (NHL.

  16. Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    Gardner, Heather L.; Izumi, Raquel; Hamdy, Ahmed; Rothbaum, Wayne; Coombes, Kevin R.; Covey, Todd; Kaptein, Allard; Gulrajani, Michael; Van Lith, Bart; Krejsa, Cecile; Coss, Christopher C.; Russell, Duncan S.; Zhang, Xiaoli; Urie, Bridget K.; London, Cheryl A.; Byrd, John C.; Johnson, Amy J.; Kisseberth, William C.

    2016-01-01

    Acalabrutinib (ACP-196) is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK) with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL). First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Acalabrutinib also inhibited proliferation in CLBL1 cells. Twenty dogs were enrolled in the clinical trial and treated with acalabrutinib at dosages of 2.5 to 20mg/kg every 12 or 24 hours. Acalabrutinib was generally well tolerated, with adverse events consisting primarily of grade 1 or 2 anorexia, weight loss, vomiting, diarrhea and lethargy. Overall response rate (ORR) was 25% (5/20) with a median progression free survival (PFS) of 22.5 days. Clinical benefit was observed in 30% (6/20) of dogs. These findings suggest that acalabrutinib is safe and exhibits activity in canine B-cell lymphoma patients and support the use of canine lymphoma as a relevant model for human non-Hodgkin lymphoma (NHL). PMID:27434128

  17. Targeting B-cell lymphomas with inhibitors of the MALT1 paracaspase.

    Science.gov (United States)

    Hailfinger, Stephan; Lenz, Georg; Thome, Margot

    2014-12-01

    The paracaspase MALT1 is an Arg-specific protease that cleaves multiple substrates to promote lymphocyte proliferation and survival. The catalytic activity of MALT1 is normally tightly regulated by antigen receptor triggering, which promotes MALT1 activation by its inducible monoubiquitination-dependent dimerization. Constitutive MALT1 activity is a hallmark of specific subsets of B-cell lymphomas, which are characterized by chromosomal translocations or point mutations that activate MALT1 or its upstream regulators. Recent findings suggest that such lymphomas may be sensitive to treatment with MALT1 inhibitors. Here we review recent progress in the understanding of MALT1 function and regulation, and the development of small molecule MALT1 inhibitors for therapeutic applications.

  18. Development tuberculous meningitis during chemotherapy for CD5-positive diffuse large B-cell lymphoma.

    Science.gov (United States)

    Teramura, Yuki; Kameda, Kazuaki; Kanda, Junya; Gomyo, Ayumi; Hayakawa, Jin; Akahoshi, Yu; Komiya, Yusuke; Harada, Naonori; Ugai, Tomotaka; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Wada, Hidenori; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Kanda, Yoshinobu

    2016-05-01

    The patient was a 62-year-old woman with CD5(+) diffuse large B-cell lymphoma. Treatment with the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) was started. On the eleventh day of the third cycle, headache and low grade fever developed. Her consciousness gradually deteriorated. Seven days after symptom onset, she was brought to the emergency department of our hospital. Cerebrospinal fluid (CSF) analysis revealed a white blood cell count of 25/μl, and a protein level of 188 mg/dl. Antibacterial and antiviral agents were administered based on a diagnosis of acute meningitis. She showed no improvement. We performed another lumbar puncture and intrathecal chemotherapy, a combination of methotrexate and dexamethasone, was administered because we suspected central nervous system involvement of lymphoma. She showed transient improvement. On day 12, we started the R-MPV regimen (rituximab, methotrexate, procarbazine, and vincristine). However, fever and disturbance of consciousness persisted. On day 20, we empirically started anti-tuberculosis treatment. Four days later, tubercle bacilli were confirmed by CSF culture after a 23-day incubation. We ultimately confirmed a diagnosis of tuberculous meningitis. Impaired cellular immunity in lymphoma patients increases the risk of tuberculosis. It is important to consider tuberculous meningitis in the differential diagnosis of a lymphoma patient presenting with meningitis.

  19. The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection.

    Science.gov (United States)

    Arcaini, Luca; Rossi, Davide; Lucioni, Marco; Nicola, Marta; Bruscaggin, Alessio; Fiaccadori, Valeria; Riboni, Roberta; Ramponi, Antonio; Ferretti, Virginia V; Cresta, Stefania; Casaluci, Gloria Margiotta; Bonfichi, Maurizio; Gotti, Manuel; Merli, Michele; Maffi, Aldo; Arra, Mariarosa; Varettoni, Marzia; Rattotti, Sara; Morello, Lucia; Guerrera, Maria Luisa; Sciarra, Roberta; Gaidano, Gianluca; Cazzola, Mario; Paulli, Marco

    2015-02-01

    Hepatitis C virus has been found to be associated with B-cell non-Hodgkin lymphomas, mostly marginal zone lymphomas and diffuse large B-cell lymphoma. Deregulation of signaling pathways involved in normal marginal zone development (NOTCH pathway, NF-κB, and BCR signaling) has been demonstrated in splenic marginal zone lymphoma. We studied mutations of NOTCH pathway signaling in 46 patients with hepatitis C virus-positive diffuse large B-cell lymphoma and in 64 patients with diffuse large B-cell lymphoma unrelated to HCV. NOTCH2 mutations were detected in 9 of 46 (20%) hepatitis C virus-positive patients, and NOTCH1 mutations in 2 of 46 (4%). By contrast, only one of 64 HCV-negative patients had a NOTCH1 or NOTCH2 mutation. The frequency of the NOTCH pathway lesions was significantly higher in hepatitis C virus-positive patients (P=0.002). The 5-year overall survival was 27% (95%CI: 5%-56%) for hepatitis C virus-positive diffuse large B-cell lymphoma patients carrying a NOTCH pathway mutation versus 62% (95%CI: 42%-77%) for those without these genetic lesions. By univariate analysis, age over 60 years, NOTCH2 mutation, and any mutation of the NOTCH pathway (NOTCH2, NOTCH1, SPEN) were associated with shorter overall survival. Mutation of the NOTCH pathway retained an independent significance (P=0.029). In conclusion, a subset of patients with hepatitis C virus-positive diffuse large B-cell lymphoma displays a molecular signature of splenic marginal zone and has a worse clinical outcome.

  20. High dose chemotherapy with autologous stem cell transplantation in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Popp, Henning

    2007-06-01

    Full Text Available Background: High-dose chemotherapy (HDT with autologous stem cell transplantation (ASCT plays an important role in the treatment of aggressive non-Hodgkin’s lymphoma (NHL. We report on a retrospective analysis of all patients with diffuse large B-cell lymphoma who were consecutively treated with HDT followed by ASCT at the University Hospital of Bonn, Germany, between 1996 and 2004. Methods: A total of 25 patients were transplanted for biopsy-proven diffuse large B-cell lymphoma (DLBCL. Eight patients received up-front HDT as first-line therapy, four patients received HDT due to incomplete response to conventional induction chemotherapy, and six patients were treated for primary refractory disease. Seven patients had recurrent lymphoma. Results: A complete remission (CR was achieved in 14 of 25 patients (56%. Estimated 3-year survival for patients treated with upfront HDT, chemosensitive patients with incomplete response to first line therapy, and patients with chemosensitive relapsed disease was 87.5%, 50.0% and 60.0%, respectively. In contrast, no patient with primary refractory disease or relapsed disease lacking chemosensitivity lived longer than 8 months. Chemosensitivity was the only significant prognostic factor for overall survival (OS in multivariate analysis. Conclusions: Our results confirm that HDT and ASCT is a highly effective therapy in patients with DLBCL leading to long-term survival in a substantial proportion of patients. Patients treated upfront for high-risk disease, incomplete response to conventional first-line therapy, or for chemosensitive relapse have a good prognosis. In contrast, patients with primary chemorefractory disease and patients with relapsed disease lacking chemosensitivity do not benefit from HDT with ASCT.

  1. Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes.

    Science.gov (United States)

    Machiela, Mitchell J; Lan, Qing; Slager, Susan L; Vermeulen, Roel C H; Teras, Lauren R; Camp, Nicola J; Cerhan, James R; Spinelli, John J; Wang, Sophia S; Nieters, Alexandra; Vijai, Joseph; Yeager, Meredith; Wang, Zhaoming; Ghesquières, Hervé; McKay, James; Conde, Lucia; de Bakker, Paul I W; Cox, David G; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R; De Roos, Anneclaire J; Brooks-Wilson, Angela R; Giles, Graham G; Melbye, Mads; Gu, Jian; Jackson, Rebecca D; Kane, Eleanor; Purdue, Mark P; Vajdic, Claire M; Albanes, Demetrius; Kelly, Rachel S; Zucca, Mariagrazia; Bertrand, Kimberly A; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M; Link, Brian K; Novak, Anne J; Dogan, Ahmet; Asmann, Yan W; Liebow, Mark; Thompson, Carrie A; Ansell, Stephen M; Witzig, Thomas E; Tilly, Hervé; Haioun, Corinne; Molina, Thierry J; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans-Olov; Roos, Göran; Bracci, Paige M; Riby, Jacques; Smith, Martyn T; Holly, Elizabeth A; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M; Severson, Richard K; Tinker, Lesley F; North, Kari E; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J; Villano, Danylo J; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R; Turner, Jenny; Southey, Melissa C; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Boeing, Heiner; Tjønneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; De Vivo, Immaculata; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Liang, Liming; Park, Ju-Hyun; Chung, Charles C; Weisenburger, Dennis D; Fraumeni, Joseph F; Salles, Gilles; Glenn, Martha; Cannon-Albright, Lisa; Curtin, Karen; Wu, Xifeng; Smedby, Karin E; de Sanjose, Silvia; Skibola, Christine F; Berndt, Sonja I; Birmann, Brenda M; Chanock, Stephen J; Rothman, Nathaniel

    2016-04-15

    Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 × 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 × 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.

  2. CCR 20th anniversary commentary: Radioactive Drones for B-cell lymphoma.

    Science.gov (United States)

    Knox, Susan J; Levy, Ronald

    2015-02-01

    In a study published in the March 1, 1996, issue of Clinical Cancer Research, Knox and colleagues (1) demonstrated the safety and efficacy of Yttirium-90 ((90)Y)-anti-CD20 monoclonal antibody therapy, as well as the benefit of preinfusion of unlabeled antibody on radiolabeled antibody biodistribution. Subsequent clinical trials with this radiolabeled antibody led to regulatory approval of this treatment for B-cell lymphoma. See related article by Knox et al., Clin Cancer Res 1996;2(3) Mar 1996; 457-70.

  3. Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Taskinen, M.; Louhimo, R.; Koivula, S.;

    2014-01-01

    Background: Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. Methods: We analysed 51 prospectively collected pretreatment...... level immunohistochemically in a trial specific tissue microarray series of 70, and in an independent validation series of 146 patients. Results: We identified 31 genes whose expression changes were strongly associated with copy number aberrations. In addition, gains of chromosomes 2p15 and 18q12.2 were...

  4. Efficacy of rituximab in gastric diffuse large B cell lymphoma patients

    Institute of Scientific and Technical Information of China (English)

    Davide; Leopardo; Giuseppe; Di; Lorenzo; Amalia; De; Renz

    2010-01-01

    AIM:To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma(DLBCL).METHODS:Sixty patients(median age:58 years)with histologically confirmed gastric DLBCL treated at four Italian institutions between 2000 and 2007,were included in this analysis.Patients were selected by stage (Ⅰ-Ⅳ,Lugano staging system),European Cooperative Oncology Group performance status(0-2)and treatment strategies.Treatment strategies were chemotherapy alone(group A,n=30)[schedule...

  5. Clinical and prognostic significance of aberrant T-cell marker expression in 225 cases of de novo diffuse large B-cell lymphoma and 276 cases of other B-cell lymphomas.

    Science.gov (United States)

    Tsuyama, Naoko; Ennishi, Daisuke; Yokoyama, Masahiro; Baba, Satoko; Asaka, Reimi; Mishima, Yuko; Terui, Yasuhito; Hatake, Kiyohiko; Takeuchi, Kengo

    2017-03-23

    Expression of T-cell markers, generally investigated for immunophenotyping of T-cell lymphomas, is also observed in several types of B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). We previously reported that CD5 expression in DLBCL is an inferior prognostic factor in the era of rituximab. However, data regarding the frequencies, histological relevance, and prognostic importance of T-cell markers other than CD5 are currently unavailable. In the present study, we comprehensively evaluated the expression of T-cell markers (CD2, CD3, CD4, CD5, CD7, and CD8) in 501 B-cell lymphomas, including 225 DLBCLs, by flow cytometry and subsequent immunohistochemistry. T-cell markers other than CD5, such as CD2, CD4, CD7, and CD8, were expressed in 27 (5%) patients, and notably, all of these cases were classified as large B-cell lymphoma subtypes: 25 DLBCLs and 2 intravascular large B-cell lymphomas. CD5 and other T-cell markers were expressed in 15% (31/225) and 10% (25/225) of DLBCL cases, respectively. Five of them co-expressed CD5 and other T-cell markers. Retrospectively analyzing the prognostic relevance of T-cell markers in 169 patients with primary DLBCL treated with rituximab-based chemotherapy, we showed that only CD5 was a strong predictor of poor survival. This study provides information about the occurrence of T-cell markers other than CD5 in B-cell lymphomas, their frequent histological subtypes, and their prognostic significance in DLBCL. CD5 was reconfirmed as a negative prognostic marker in DLBCL patients receiving rituximab-inclusive chemotherapy, whereas T-cell markers other than CD5 were found to have no impact on clinicopathological and survival analyses.

  6. Apoptotic induction in B-cell acute lymphoblastic leukemia cell lines treated with a protein kinase Cβ inhibitor.

    Science.gov (United States)

    Saba, Nakhle S; Levy, Laura S

    2011-05-01

    B-cell acute lymphoblastic leukemia (B-ALL) in adults exhibits a 5-year disease-free survival rate of only 25-40% after currently available treatment. Protein kinase Cβ (PKCβ) is under active consideration as a rational therapeutic target in several B-cell malignancies, but studies of its possible utility in B-ALL are lacking. Expression of PKCβ1 and PKCβ2 isoforms was demonstrated in five B-ALL cell lines characterized by distinctive chromosomal translocations, and sensitivity to PKCβ-selective inhibition was examined. Inhibitor treatment resulted in a dose-dependent reduction in viability in all cell lines, although pro-B ALL with t(4;11)(q21;q23) was most sensitive. Apoptotic induction was evident after 24-48 h of treatment, and an inhibition of cell cycle progression was detected in one cell line. Treatment resulted in a rapid induction of poly(ADP-ribose) polymerase (PARP) cleavage, indicating caspase-3-mediated apoptosis, and a rapid reduction in phosphorylation of AKT and its downstream target glycogen synthase kinase 3β (GSK3β). These results indicate that PKCβ targeting should be considered as a potential treatment option in B-ALL.

  7. Homing of human B cells to lymphoid organs and B-cell lymphoma engraftment are controlled by cell adhesion molecule JAM-C.

    Science.gov (United States)

    Doñate, Carmen; Ody, Christiane; McKee, Thomas; Ruault-Jungblut, Sylvie; Fischer, Nicolas; Ropraz, Patricia; Imhof, Beat A; Matthes, Thomas

    2013-01-15

    Junctional adhesion molecule C (JAM-C) is expressed by vascular endothelium and human but not mouse B lymphocytes. The level of JAM-C expression defines B-cell differentiation stages and allows the classification of marginal zone-derived (JAM-C-positive) and germinal center-derived (JAM-C-negative) B-cell lymphomas. In the present study, we investigated the role of JAM-C in homing of human B cells, using a xenogeneic nonobese diabetic/severe combined immunodeficient mouse model. Treatment with anti-JAM-C antibodies in short-term experiments reduced migration of normal and malignant JAM-C-expressing B cells to bone marrow, lymph nodes, and spleen. Blocking homing to the spleen is remarkable, as most other antiadhesion antibodies reduce homing of B cells only to bone marrow and lymph nodes. Long-term administration of anti-JAM-C antibodies prevented engraftment of JAM-Cpos lymphoma cells in bone marrow, spleen, and lymph nodes of mice. Plasmon resonance studies identified JAM-B as the major ligand for JAM-C, whereas homotypic JAM-C interactions remained at background levels. Accordingly, anti-JAM-C antibodies blocked adhesion of JAM-C-expressing B cells to their ligand JAM-B, and immunofluorescence analysis showed the expression of JAM-B on murine and human lymphatic endothelial cells. Targeting JAM-C could thus constitute a new therapeutic strategy to prevent lymphoma cells from reaching supportive microenvironments not only in the bone marrow and lymph nodes but also in the spleen.

  8. Immunotherapy for B-cell lymphoma: current status and prospective advances

    Directory of Open Access Journals (Sweden)

    Nurit eHollander

    2012-01-01

    Full Text Available Therapy for non-Hodgkin's lymphoma has progressed significantly over the last decades. However, the majority of patients remain incurable, and novel therapies are needed. Because immunotherapy ideally offers target selectivity, an ever increasing number of immunotherapies, both passive and active, are undergoing development. The champion of passive immunotherapy to date is the anti-CD20 monoclonal antibody rituximab that revolutionized the standard of care for lymphoma. The great success of rituximab catalyzed the development of new passive immunotherapy strategies that are currently undergoing clinical evaluation. These include improvement of rituximab efficacy, newer generation anti-CD20 antibodies, drug-conjugated and radiolabelled anti-CD20 antibodies, monoclonal antibodies targeting non-CD20 lymphoma antigens, and bispecific antibodies. Active immunotherapy aims at inducing long-lasting antitumor immunity, thereby limiting the likelihood of relapse. Current clinical studies of active immunotherapy for lymphoma consist largely of vaccination and immune checkpoint blockade. A variety of protein- and cell-based vaccines are being tested in ongoing clinical studies. Recently completed phase III clinical trials of an idiotype protein vaccine suggest that the vaccine may have clinical activity in a subset of patients. Efforts to enhance the efficacy of active immunotherapy are ongoing with an emphasis on optimization of antigen delivery and presentation of vaccines and modulation of the immune system toward counteracting immunosuppression, using antibodies against immune regulatory checkpoints. This article discusses results of the various immunotherapy approaches applied to date for B-cell lymphoma and the ongoing trials to improve their effect.

  9. B-cell receptor-driven MALT1 activity regulates MYC signaling in mantle cell lymphoma.

    Science.gov (United States)

    Dai, Beiying; Grau, Michael; Juilland, Mélanie; Klener, Pavel; Höring, Elisabeth; Molinsky, Jan; Schimmack, Gisela; Aukema, Sietse M; Hoster, Eva; Vogt, Niklas; Staiger, Annette M; Erdmann, Tabea; Xu, Wendan; Erdmann, Kristian; Dzyuba, Nicole; Madle, Hannelore; Berdel, Wolfgang E; Trneny, Marek; Dreyling, Martin; Jöhrens, Korinna; Lenz, Peter; Rosenwald, Andreas; Siebert, Reiner; Tzankov, Alexandar; Klapper, Wolfram; Anagnostopoulos, Ioannis; Krappmann, Daniel; Ott, German; Thome, Margot; Lenz, Georg

    2017-01-19

    Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by poor clinical outcome. Recent studies revealed the importance of B-cell receptor (BCR) signaling in maintaining MCL survival. However, it remains unclear which role MALT1, an essential component of the CARD11-BCL10-MALT1 complex that links BCR signaling to the NF-κB pathway, plays in the biology of MCL. Here we show that a subset of MCLs is addicted to MALT1, as its inhibition by either RNA or pharmacologic interference induced cytotoxicity both in vitro and in vivo. Gene expression profiling following MALT1 inhibition demonstrated that MALT1 controls an MYC-driven gene expression network predominantly through increasing MYC protein stability. Thus, our analyses identify a previously unappreciated regulatory mechanism of MYC expression. Investigating primary mouse splenocytes, we could demonstrate that MALT1-induced MYC regulation is not restricted to MCL, but represents a common mechanism. MYC itself is pivotal for MCL survival because its downregulation and pharmacologic inhibition induced cytotoxicity in all MCL models. Collectively, these results provide a strong mechanistic rationale to investigate the therapeutic efficacy of targeting the MALT1-MYC axis in MCL patients.

  10. High Frequency of Bone Marrow Involvement in Intravascular Large B-Cell Lymphoma.

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    Wang, Jianchao; Ding, Wenshuang; Gao, Limin; Yao, Wenqing; Chen, Min; Zhao, Sha; Liu, Weiping; Zhang, Wenyan

    2017-04-01

    Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma. Thirteen cases of IVLBCL with a median age of 56 years were analyzed retrospectively. Nonspecific symptoms such as fever and hepatosplenomegaly were the most common manifestations, and the bone marrow was usually involved in 8/13 (61.5%) cases. All tumors expressed CD20, and 12/13 (92.3%) of the tumors exhibited a nongerminal center phenotype by Hans algorithm. CD5 was expressed in 3/12 (25%) of the tumors. MYC was negative in all cases, and BCL2 was positive in 10/12 (83.3%) cases. Cytogenetic analysis revealed 5 cases that did not have rearrangements in either the MYC or the BCL2 gene. No association with Epstein-Barr virus was found. Seven of 11 patients received chemotherapy. The median survival time was 6 months. Patients with hemophagocytic syndrome had poor prognoses. Our study demonstrates that IVLBCL has a poor clinical outcome with a high frequency of bone marrow involvement and that the MYC gene may not play an important role in the poor prognosis of IVLBCL.

  11. Etoposide, Filgrastim, and Plerixafor in Improving Stem Cell Mobilization in Treating Patients With Non-Hodgkin Lymphoma

    Science.gov (United States)

    2016-09-15

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  12. Salvia Hispanica Seed in Reducing Risk of Disease Recurrence in Patients With Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-01-26

    Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Adult T-Cell Leukemia/Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; B Lymphoblastic Leukemia/Lymphoma; Blastic Plasmacytoid Dendritic Cell Neoplasm; Burkitt Leukemia; Central Nervous System Lymphoma; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Diffuse Large B-Cell Lymphoma; Enteropathy-Associated T-Cell Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3 Follicular Lymphoma; Hepatosplenic T-Cell Lymphoma; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Mycosis Fungoides; Nasal Type Extranodal NK/T-Cell Lymphoma; Nodal Marginal Zone Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Post-Transplant Lymphoproliferative Disorder; Primary Cutaneous Anaplastic Large Cell Lymphoma; Primary Effusion Lymphoma; Sezary Syndrome; Splenic Marginal Zone Lymphoma; Subcutaneous Panniculitis-Like T-Cell Lymphoma; Systemic Anaplastic Large Cell Lymphoma; T Lymphoblastic Leukemia/Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  13. Secondary infiltration of the central nervous system in patients with diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Talita Maira Bueno da Silveira da Rocha

    2013-01-01

    Full Text Available OBJECTIVE: To investigate the incidence and risk factors of infiltration of the central nervous system after the initial treatment of diffuse large B-cell lymphoma in patients treated at Santa Casa de Misericórdia de São Paulo. METHODS: A total of 133 patients treated for diffuse large B-cell lymphoma from January 2001 to April 2008 were retrospectively analyzed in respect to the incidence and risk factors of secondary central nervous system involvement of lymphoma. Intrathecal prophylaxis was not a standard procedure for patients considered to be at risk. This analysis includes patients whether they received rituximab as first-line treatment or not. RESULTS: Nine of 133 (6.7% patients developed central nervous system disease after a mean observation time of 29 months. The median time to relapse or progression was 7.9 months after diagnosis and all but one patient died despite the treatment administered. Twenty-six (19.5% patients of this cohort received rituximab as first-line treatment and nine (7.1% received intrathecal chemoprophylaxis. Of the nine patients that relapsed, seven (77.7% had parenchymal central nervous system involvement; seven (77.7% had stage III or IV disease; one (11.1% had bone marrow involvement; two (22.2% had received intrathecal chemoprophylaxis; and 3 (33.3% had taken rituximab. In a multivariate analysis, the risk factors for this infiltration were being male, previous use of intrathecal chemotherapy and patients that were refractory to initial treatment. CONCLUSION: Central nervous system infiltration in this cohort is similar to that of previous reports in the literature. As this was a small cohort with a rare event, only three risk factors were important for this infiltration

  14. Antiviral therapy of hepatitis C as curative treatment of indolent B-cell lymphoma

    Science.gov (United States)

    Merli, Michele; Carli, Giuseppe; Arcaini, Luca; Visco, Carlo

    2016-01-01

    The association of hepatitis C virus (HCV) and B-cell non-Hodgkin lymphomas (NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by interventional studies demonstrating the capability of antiviral treatment (AT) with interferon (IFN) with or without ribavirin to induce the regression of indolent lymphomas, especially of marginal-zone origin. In the largest published retrospective study (100 patients) the overall response rate (ORR) after first-line IFN-based AT was 77% (44% complete responses) and responses were sustainable (median duration of response 33 mo). These results were confirmed by a recent meta-analysis on 254 patients, demonstrating an ORR of 73%. Moreover this analysis confirmed the highly significant correlation between the achievement of viral eradication sustained virological response (SVR) and hematological responses. Two large prospective studies demonstrated that AT is associated with improved survival and argue in favor of current guidelines’ recommendation of AT as preferential first-line option in asymptomatic patients with HCV-associated indolent NHL. The recently approved direct-acting antiviral agents (DAAs) revolutionized the treatment of HCV infection, leading to SVR approaching 100% in all genotypes. Very preliminary data of IFN-free DAAs therapy in indolent HCV-positive NHL seem to confirm their activity in inducing lymphoma regression.

  15. Intravascular Large B-Cell Lymphoma Diagnosed on Prostate Biopsy: A Case Report

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    Nazan Özsan

    2014-12-01

    Full Text Available Intravascular large B-cell lymphoma (IVLBCL is a very rare type of non-Hodgkin lymphoma, usually affecting elderly patients and characterized by selective infiltration of neoplastic cells within blood vessels’ lumina. IVLBCL diagnosed with prostatic involvement is extremely rare. We report a patient of 65 years old, having mostly neurological complaints but diagnosed with IVLBCL upon histopathological examination of transurethral prostate resection material, which revealed large neoplastic cell infiltration totally limited within the lumens of small vessels. By immunohistochemistry, neoplastic cell infiltration was positive with MUM1, bcl-6, and bcl-2 and negative with ALK1, CD10, and CD30, with a high Ki-67 proliferation index. CD34 and CD31 staining showed expression in endothelial cells, highlighting the intravascular nature of neoplastic infiltrate. The patient unfortunately refused to receive treatment and died of the disease 8 months after the diagnosis. IVLBCL, though very rare, should be considered in differential diagnosis of all organ biopsies with intravascular infiltration. Further improvements in the understanding of the pathogenesis and biology of this rare type of lymphoma are mandatory.

  16. Relevance of ID3-TCF3-CCND3 pathway mutations in pediatric aggressive B-cell lymphoma treated according to the NHL-BFM protocols.

    Science.gov (United States)

    Rohde, Marius; Bonn, Bettina R; Zimmermann, Martin; Lange, Jonas; Möricke, Anja; Klapper, Wolfram; Oschlies, Ilske; Szczepanowski, Monika; Nagel, Inga; Schrappe, Martin; Loeffler, Markus; Siebert, Reiner; Reiter, Alfred; Burkhardt, Birgit

    2017-02-16

    Mature B-cell Non-Hodgkin lymphoma is the most common subtype of Non-Hodgkin lymphoma in childhood and adolescence. B-cell Non-Hodgkin lymphoma are further classified into histological subtypes, with Burkitt lymphoma and Diffuse large B-cell lymphoma being the most common subgroups in pediatric patients. Translocations involving the MYC oncogene are known as relevant but not sufficient hit for Burkitt lymphoma pathogenesis. Recently published large-scale next-generation sequencing studies unveiled sets of additional recurrently mutated genes in samples of pediatric and adult B-cell Non-Hodgkin lymphoma patients. ID3, TCF3 and CCND3 are potential drivers of Burkitt-lymphomagenesis. In the present study frequency and clinical relevance of mutations in ID3, TCF3 and CCND3 were analyzed within a well-defined cohort of 84 uniformly diagnosed and treated pediatric B-cell Non-Hodgkin lymphoma patients of the Berlin-Frankfurt-Munster group (NHL-BFM). Mutation frequency was 78% (ID3), 13% (TCF3) and 36% (CCND3) in Burkitt lymphoma (including Burkitt leukemia). ID3 and CCND3 mutations were associated with more advanced stages of the disease in MYC rearrangement positive Burkitt lymphoma. In conclusion ID3-TCF3-CCND3 pathway genes are mutated in more than 88% of MYC-rearranged pediatric B-cell Non-Hodgkin lymphoma and the pathway may represent a highly relevant second hit of Burkitt lymphoma pathogenesis especially in children and adolescents.

  17. HSP90 promotes Burkitt lymphoma cell survival by maintaining tonic B-cell receptor signaling.

    Science.gov (United States)

    Walter, Roland; Pan, Kuan-Ting; Doebele, Carmen; Comoglio, Federico; Tomska, Katarzyna; Bohnenberger, Hanibal; Young, Ryan M; Jacobs, Laura; Keller, Ulrich; Bönig, Halvard; Engelke, Michael; Rosenwald, Andreas; Urlaub, Henning; Staudt, Louis M; Serve, Hubert; Zenz, Thorsten; Oellerich, Thomas

    2017-02-02

    Burkitt lymphoma (BL) is an aggressive B-cell neoplasm that is currently treated by intensive chemotherapy in combination with anti-CD20 antibodies. Because of their toxicity, current treatment regimens are often not suitable for elderly patients or for patients in developing countries where BL is endemic. Targeted therapies for BL are therefore needed. In this study, we performed a compound screen in 17 BL cell lines to identify small molecule inhibitors affecting cell survival. We found that inhibitors of heat shock protein 90 (HSP90) induced apoptosis in BL cells in vitro at concentrations that did not affect normal B cells. By global proteomic and phosphoproteomic profiling, we show that, in BL, HSP90 inhibition compromises the activity of the pivotal B-cell antigen receptor (BCR)-proximal effector spleen tyrosine kinase (SYK), which we identified as an HSP90 client protein. Consistently, expression of constitutively active TEL-SYK counteracted the apoptotic effect of HSP90 inhibition. Together, our results demonstrate that HSP90 inhibition impairs BL cell survival by interfering with tonic BCR signaling, thus providing a molecular rationale for the use of HSP90 inhibitors in the treatment of BL.

  18. Bortezomib and Filgrastim in Promoting Stem Cell Mobilization in Patients With Non-Hodgkin Lymphoma or Multiple Myeloma Undergoing Stem Cell Transplant

    Science.gov (United States)

    2016-04-19

    Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular

  19. Inhibition of MALT1 protease activity is selectively toxic for activated B cell-like diffuse large B cell lymphoma cells.

    Science.gov (United States)

    Ferch, Uta; Kloo, Bernhard; Gewies, Andreas; Pfänder, Vera; Düwel, Michael; Peschel, Christian; Krappmann, Daniel; Ruland, Jürgen

    2009-10-26

    Diffuse large B cell lymphoma (DLBCL) is the most common type of lymphoma in humans. The aggressive activated B cell-like (ABC) subtype of DLBCL is characterized by constitutive NF-kappaB activity and requires signals from CARD11, BCL10, and the paracaspase MALT1 for survival. CARD11, BCL10, and MALT1 are scaffold proteins that normally associate upon antigen receptor ligation. Signal-induced CARD11-BCL10-MALT1 (CBM) complexes couple upstream events to IkappaB kinase (IKK)/NF-kappaB activation. MALT1 also possesses a recently recognized proteolytic activity that cleaves and inactivates the negative NF-kappaB regulator A20 and BCL10 upon antigen receptor ligation. Yet, the relevance of MALT1 proteolytic activity for malignant cell growth is unknown. Here, we demonstrate preassembled CBM complexes and constitutive proteolysis of the two known MALT1 substrates in ABC-DLBCL, but not in germinal center B cell-like (GCB) DLBCL. ABC-DLBCL cell treatment with a MALT1 protease inhibitor blocks A20 and BCL10 cleavage, reduces NF-kappaB activity, and decreases the expression of NF-kappaB targets genes. Finally, MALT1 paracaspase inhibition results in death and growth retardation selectively in ABC-DLBCL cells. Thus, our results indicate a growth-promoting role for MALT1 paracaspase activity in ABC-DLBCL and suggest that a pharmacological MALT1 protease inhibition could be a promising approach for lymphoma treatment.

  20. Transformation of a Cutaneous Follicle Center Lymphoma to a Diffuse Large B-Cell Lymphoma—An Unusual Presentation

    Directory of Open Access Journals (Sweden)

    J. Dias Coelho

    2010-01-01

    Full Text Available Primary cutaneous follicle center lymphoma (PCFCL is characterized by a proliferation of follicle center cells in the skin. A definitive diagnosis is frequently delayed because of difficulties in interpretation of the histopathologic findings. It has an excellent prognosis with a 5-year survival over 95% and its risk of transformation has not been established. We describe a case report of man with a gastric diffuse large B-cell lymphoma (DLBCL referred to our clinic because of nodules in the back that had gradually developed over a period of 10 years. A biopsy performed 3 years before was interpreted as reactive follicular hyperplasia. A new skin biopsy revealed a diffuse large B-cell lymphoma and immunoglobulin heavy chain gene rearrangements from the initial skin biopsy (PCBCL and the DLBCL gastric biopsy were studied by polymerase chain reaction and an identical clonal rearrangement was detected which was highly suggestive of a transformation lymphoma.

  1. CD7 Positive Diffuse Large B-Cell Lymphoma Arising in a Background of Follicular Lymphoma: A Case Report and Review of the Literature

    Science.gov (United States)

    Rashidi, Hooman H.

    2016-01-01

    Diffuse large B-cell lymphoma (DLBCL) is a neoplasm of large B-lymphocytes with a diffuse growth pattern. The neoplastic cells express B-cell markers such as CD20 and PAX-5 and there may be coexpression of BCL-2, BCL-6, CD10, and MUM-1. With the exception of CD5, other T-cell markers are not commonly expressed in this neoplasm. Here, we describe the first reported case of a DLBCL with abnormal expression CD7 arising in a background of follicular lymphoma in an 81-year-old male who presented with a nontender left axillary mass. Additionally, no other T-cell antigens were expressed in this B-cell lymphoma. Expression of CD7 in DLBCL is exceptionally rare and its prognostic significance is unknown. Here, we describe this rare case with review of literature of known DLBCLs with expression of T-cell antigens.

  2. Treatment of B-cells non-Hodgkin lymphomas with combined immunochemotherapy: ability to treatment optimization

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    N. V. Smirnova

    2015-01-01

    Full Text Available The results of two consecutive multicenter clinical trials enrolled 241 patient with childhood mature B-cells non-Hodgkin lymphomas/leukemia are presented. Patients received treatment according B-NHL 2004mab protocol (n = 83 and B-NHL 2010M (n = 158 with combined immunochemotherapy (ICT in Russian and Belarus pediatric clinics from 2004 to 2015 years. Primary patients with different mature B-NHL (Burkitt lymphoma/leukemia, diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma (DLBCL and PMBCL aged from 2 to 18 years are included in the studies.Protocol B-NHL 2004mab for treatment of children and adolescents with B-NHL/B-AL, stage III and IV, includes a combination of chemotherapy (PCT and rituximab – an antibody against the B-cells receptor CD20. PCT courses similar to those in the B-NHL BFM90 protocol (group III with the exception of methotrexate dose in induction courses, reduced to 1 g/m2 /24 h in order to reduce toxicity. Rituximab (Mabthera, 375 mg/m2 /h used for the first time in the treatment of children and adolescents with B-NHL. Of the 83 patients included, clinical remission was achieved in 77 (92.8 %. With a median follow time of 51.6 months, remission continued in 23 (85.2 % patients with B-AL, in 32 (88.9 % patients with LB and 19 (95.0 % patients – with DLBCL. With median follow time of 65.2 months, event-free and overall survival was 84 ± 6 and 82 ± 8 %, respectively.Based on previous experience in order to further optimize B-NHL treatment, new protocol B-NHL 2010M with effect-adapted therapy and improvement of stratification risk group criteria was proposed. Overall survival in patients of 1st and 2nd risk groups with full implementation of diagnosis and treatment is approaching 100 %. In interim analysis of 3rd risk group patients, pOS was 88 ± 3 %. The incidence of induction death (infections, metabolic complications remains within 2.7 % (n = 4; refractory cases (n = 2; 1.3 % and relapses (n = 4; 2

  3. Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma

    Science.gov (United States)

    Ford, Catriona A.; Petrova, Sofia; Pound, John D.; Voss, Jorine J.L.P.; Melville, Lynsey; Paterson, Margaret; Farnworth, Sarah L.; Gallimore, Awen M.; Cuff, Simone; Wheadon, Helen; Dobbin, Edwina; Ogden, Carol Anne; Dumitriu, Ingrid E.; Dunbar, Donald R.; Murray, Paul G.; Ruckerl, Dominik; Allen, Judith E.; Hume, David A.; van Rooijen, Nico; Goodlad, John R.; Freeman, Tom C.; Gregory, Christopher D.

    2015-01-01

    Summary Background Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. Results Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased “in situ transcriptomics” analysis—gene expression profiling of laser-captured TAMs to establish their activation signature in situ—we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. Conclusions In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy. PMID:25702581

  4. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures

    DEFF Research Database (Denmark)

    Hu, Shimin; Xu-Monette, Zijun Y; Tzankov, Alexander;

    2013-01-01

    Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes based on gene expression signatures. In this study, we analyzed 893 de novo DLBCL patients treated with R-CHOP (rituximab, cyclo...

  5. Primary cutaneous large B-cell lymphoma, leg type: Report of two cases and review of literature

    Directory of Open Access Journals (Sweden)

    Santosh Kumar Mondal

    2012-01-01

    Full Text Available Primary cutaneous large B-cell lymphoma, leg type (PCLBCL-LT, is very rare neoplasm presenting on and confined to leg(s. PCLBCL-LT is distinguished from other type of primary cutaneous B-cell lymphoma (PCBCL by its frequent relapses and poorer prognosis. We report, two cases of PCLBCL-LT, occurring in two younger patients compared to published cases in literature. Both the patients were treated with chemotherapy and local radiotherapy. During the 1-year follow-up period one patient presented with extracutaneous dissemination and succumbed. The other patient is symptom free and follow-up period was uneventful.

  6. Tracheal ulcer due to Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

    Science.gov (United States)

    Ito, Takeo; Fujisaki, Hideaki; Nishio, Suehiro; Hiroshige, Shigeo; Miyazaki, Eishi; Kadota, Jun-ichi

    2014-03-01

    A 74-year-old man was referred to our hospital because of a tracheal stenosis circumscribed with soft tissue density and a left pulmonary nodule. Open biopsy of a right submandibular lymph node revealed diffuse large B-cell lymphoma, and the malignant cells were positive for Epstein-Barr virus gene products. Bronchofiberscopy revealed a tracheal necrotizing ulcer. After chemotherapy, the tracheal ulcer resolved. To our knowledge, this is the first report of a case of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly with a tracheal ulcer.

  7. Clinical and Biologic Significance of MYC Genetic Mutations in De Novo Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Deng, Qipan; Manyam, Ganiraju C

    2016-01-01

    PURPOSE: MYC is a critical driver oncogene in many cancers, and its deregulation in the forms of translocation and overexpression has been implicated in lymphomagenesis and progression of diffuse large B-cell lymphoma (DLBCL). The MYC mutational profile and its roles in DLBCL are unknown. This st......PURPOSE: MYC is a critical driver oncogene in many cancers, and its deregulation in the forms of translocation and overexpression has been implicated in lymphomagenesis and progression of diffuse large B-cell lymphoma (DLBCL). The MYC mutational profile and its roles in DLBCL are unknown...

  8. A Rare Case of Gastric Variceal Hemorrhage Secondary to Infiltrative B-Cell Lymphoma

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    Adrienne Lenhart

    2016-10-01

    Full Text Available Portal hypertension commonly arises in the setting of advanced liver cirrhosis and is the consequence of increased resistance within the portal vasculature. Less commonly, left-sided noncirrhotic portal hypertension can develop in a patient secondary to isolated obstruction of the splenic vein. We present a rare case of left-sided portal hypertension and isolated gastric varices in a patient with large B-cell lymphoma, who was treated with splenic artery embolization. The patient is a 73-year-old male with no previous history of liver disease, who presented with coffee ground emesis and melena. On admission to hospital, he was found to have a hemoglobin level of 3.4 g/l. Emergent esophagogastroduodenoscopy showed isolated bleeding gastric varices (IGV1 by Sarin classification in the fundus and cardia with subsequent argon plasma coagulation injection. He was transferred to our tertiary center where work-up revealed normal liver function tests, and abdominal ultrasound showed patent hepatic/portal vasculature without cirrhosis. MRI demonstrated a large heterogeneously enhancing mass in the pancreatic tail, with invasion into the spleen and associated splenic vein thrombosis. Surgery consultation was obtained, but urgent splenectomy was not recommended. The patient instead underwent splenic artery embolization to prevent future bleeding from his known gastric varices. Pathology from a CT-guided biopsy was consistent with diffuse large B-cell lymphoma. PET imaging showed uptake in the splenic hilum/pancreatic tail region with no additional metastatic involvement. He was evaluated by the Hematology Department to initiate R-CHOP chemotherapy. During his outpatient follow-up, he reported no further episodes of melena or hematemesis. To the best of our knowledge, there have only been two published case reports of large B-cell lymphoma causing upper gastrointestinal bleeding from isolated gastric varices. These cases were treated with splenectomy or

  9. Rituximab in the treatment of B-cell non-Hodgkin lymphoma, focus on outcomes and comparative effectiveness

    Directory of Open Access Journals (Sweden)

    Firas Badin

    2010-04-01

    Full Text Available Firas Badin, John HayslipUniversity of Kentucky, Markey Cancer Center, Lexington, KY, USAAbstract: Rituximab is an important and well established component in the treatment of many patients with B-cell non-Hodgkin lymphoma. In this paper we review recent clinical trials investigating the addition of rituximab to standard chemotherapy regimens for treatment of patients with diffuse large B cell lymphoma and follicular lymphoma. This report focuses upon treatment efficacy, quality of life, and safety of rituximab or rituximab-containing regimens. More uniquely, we review economic aspects of lymphoma treatments, including the cost of standard chemotherapy regimens with or without rituximab, cost effectiveness of rituximab in both induction and maintenance treatment, and lymphoma’s impacts on patient’s productivity and their caregivers. We conclude that adding rituximab to standard chemotherapy treatment for patients with B-cell non-Hodgkin lymphoma is safe and cost-effective in numerous settings during both induction and maintenance therapies. Despite extensive review of the literature, many important questions have yet to be answered in the rituximab era and these represent important directions for future study.Keywords: rituximab, lymphoma, cost effectiveness, transplant, safety

  10. Concomitant sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman Disease and diffuse large B-cell lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Moore James C

    2008-03-01

    Full Text Available Abstract Introduction Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman Disease, is a rare and benign source of lymphadenopathy first described in 1969, which mimics neoplastic processes. This disease commonly presents in children and young adults with supra-diaphragmatic lymphadenopathy or extranodal lesions consisting of tissue infiltrates composed of a polyclonal population of histiocytes. Since its description greater than 400 cases have been described, sometimes in patients with a variety of treated and untreated neoplastic diseases. However, the literature contains reports of only 19 cases of Rosai-Dorfman Disease in association with lymphomas, Hodgkin's or non-Hodgkin's. The majority of these cases have the two diagnoses, malignant lymphoma and Rosai-Dorfman Disease, separated in time. Interestingly, infradiaphragmatic lymphadenopathy was a feature in the majority of previously reported cases of Rosai-Dorfman Disease and non-Hodgkin's lymphoma. Case presentation This report provides details of a case with co-existing sinus histiocytosis with massive lymphadenopathy and diffuse large B cell non-Hodgkin's lymphoma. This case is the fifth described case of simultaneous Rosai-Dorfman Disease and concurrent non-Hodgkin's lymphoma. Unfortunately, the diagnosis of a clinically aggressive diffuse large B cell lymphoma was made at autopsy. The aggressive biological behavior of the diffuse large B cell lymphoma in this patient may have been related to the underlying immune dysregulation believed to be part of the pathophysiology of Rosai-Dorfman Disease. Conclusion Taken together this report and the preceding reports of Rosai-Dorfman Disease and non-Hodgkin's lymphoma suggests that in cases with a diagnosis of Rosai-Dorfman Disease in the setting of prominent infradiaphragmatic lymphadenopathy, clinicians should maintain a high index of suspicion for the presence of occult non-Hodgkin's lymphoma especially if the

  11. Concurrent acute myeloid leukemia and T lymphoblastic lymphoma in a patient with rearranged PDGFRB genes

    Directory of Open Access Journals (Sweden)

    Chang Hung

    2012-02-01

    Full Text Available Abstract Concurrent hematologic malignancies are relatively rare. We encountered a case of concurrent acute myeloid leukemia (AML and T lymphoblastic lymphoma. The bone marrow chromosome analysis showed the karyotype 46, XY, t(5;12(q33;p13, which indicated presence of PDGFRB gene translocations. Therefore, this disease belongs to the new WHO category of myeloid and lymphoid neoplasms with abnormalities in PDGFRA, PDGFRB and FGFR1 genes. Although such genetic mutations are prone to multi-lineage differentiation, the present case is in fact the first report of concurrent AML and T lymphoblastic lymphoma involving PDGFRB mutations. The patient was treated with cytarabine and daunomycin in combination with high dose dexamethasone. Allogeneic stem cell transplantation was performed after successful remission induction for both entities. The patient eventually died of chronic graft-versus-host-disease related infection. Based on such an experience, we suggest the decision of stem cell transplantation should be weighed carefully against the risks, especially when tyrosine kinase inhibitors are safe and potentially effective in dealing with such entities.

  12. Retinoid-related orphan receptor γ (RORγ) adult induced knockout mice develop lymphoblastic lymphoma.

    Science.gov (United States)

    Liljevald, Maria; Rehnberg, Maria; Söderberg, Magnus; Ramnegård, Marie; Börjesson, Jenny; Luciani, Donatella; Krutrök, Nina; Brändén, Lena; Johansson, Camilla; Xu, Xiufeng; Bjursell, Mikael; Sjögren, Anna-Karin; Hornberg, Jorrit; Andersson, Ulf; Keeling, David; Jirholt, Johan

    2016-11-01

    RORγ is a nuclear hormone receptor which controls polarization of naive CD4(+) T-cells into proinflammatory Th17 cells. Pharmacological antagonism of RORγ has therapeutic potential for autoimmune diseases; however, this mechanism may potentially carry target-related safety risks, as mice deficient in Rorc, the gene encoding RORγ, develop T-cell lymphoma with 50% frequency. Due to the requirement of RORγ during development, the Rorc knockout (KO) animals lack secondary lymphoid organs and have a dysregulation in the generation of CD4+ and CD8+ T cells. We wanted to extend the evaluation of RORγ deficiency to address the question whether lymphomas, similar to those observed in the Rorc KO, would develop in an animal with an otherwise intact adult immune system. Accordingly, we designed a conditional RORγ knockout mouse (Rorc CKO) where the Rorc locus could be deleted in adult animals. Based on these studies we can confirm that these animals also develop lymphoma in a similar time frame as embryonic Rorc knockouts. This study also suggests that in animals where the gene deletion is incomplete, the thymus undergoes a rapid selection process replacing Rorc deficient cells with remnant thymocytes carrying a functional Rorc locus and that subsequently, these animals do not develop lymphoblastic lymphoma.

  13. Diffuse Large B-Cell Lymphoma in Human T-Lymphotropic Virus Type 1 Carriers

    Directory of Open Access Journals (Sweden)

    Brady E. Beltran

    2012-01-01

    Full Text Available We describe the clinical and pathological characteristics of seven patients who were human T-lymphotropic virus type 1 (HTLV-1 carriers and had a pathological diagnosis of de novo diffuse large B-cell lymphoma. Interestingly, three of our cases showed positive expression of Epstein-Barr-virus, (EBV- encoded RNA within the tumor cells indicating a possible interaction between these two viruses. Furthermore, our three EBV-positive cases presented with similar clinical characteristics such as early clinical stage and low-risk indices. To the best of our knowledge, this is the first case series describing the characteristics of HTLV-1-positive DLBCL patients. The potential relationship between HTLV-1 and EBV should be further explored.

  14. Wntless (GPR177) expression correlates with poor prognosis in B-cell precursor acute lymphoblastic leukemia via Wnt signaling.

    Science.gov (United States)

    Chiou, Shyh-Shin; Wang, Li-Ting; Huang, Shih-Bo; Chai, Chee-Yin; Wang, Shen-Nien; Liao, Yu-Mei; Lin, Pei-Chin; Liu, Kwei-Yan; Hsu, Shih-Hsien

    2014-10-01

    B-cell precursor acute lymphoblastic leukemia (BCP ALL) is the most common childhood leukemia, with a cure rate of 80%. Nevertheless, disease relapse is the most important prognostic factor for the disease outcome. We aimed to elucidate the role of Wnt secretion-regulating protein, Wntless (Wls)/GPR177, on disease outcome in pediatric patients with BCP ALL, and assess its pathogenetic role in the regulation of the disease. Wls expression was characterized and correlated with Wnt pathway signaling in the bone marrow leukemia cells isolated from 44 pediatric patients with BCP ALL. The overexpression of Wls was detected in leukemia cells and was significantly correlated with the disease relapse and poor survival in the patients. The high expression of Wls also correlated with the Wnt expression and consequent downstream signaling activation, which was shown to provide essential proliferation, transformation and anti-apoptotic activity during leukemogenesis. These results indicated that Wls played an essential role in disease relapse and poor survival in patients with BCP ALL. Therefore, Wls may provide a potential future therapeutic target, particularly for patients who do not respond to existing therapies and suffer relapse.

  15. Cyclin D1 (Bcl-1, PRAD1) protein expression in low-grade B-cell lymphomas and reactive hyperplasia.

    Science.gov (United States)

    Yang, W. I.; Zukerberg, L. R.; Motokura, T.; Arnold, A.; Harris, N. L.

    1994-01-01

    Mantle cell (centrocytic) lymphoma (MCL) and occasional cases of B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia (B-SLL/CLL) show a characteristic translocation, t(11:14)(q13;q32) involving rearrangement of the Bcl-1 region. Recently it was shown that the key Bcl-1 region oncogene is cyclin D1/PRAD1; cyclin D1 mRNA was shown to be overexpressed in cases of MCL. We examined cyclin D1 protein expression in low-grade B-cell lymphomas and reactive lymphoid hyperplasias using polyclonal and monoclonal antibodies to cyclin D1 protein. Definite nuclear staining was seen in 15 of 15 MCLs, 1 of 7 B-SLL/CLLs, 0 of 7 reactive hyperplasias, 0 of 10 follicular lymphomas, and 0 of 4 lymphomas of mucosa-associated lymphoid tissue using immunoperoxidase stains on paraffin-embedded sections. Best results were obtained with the affinity-purified polyclonal antibody on microwave-treated, formalin-fixed, paraffin-embedded tissue. MCLs showed diffuse nuclear staining, whereas the one positive B-SLL/CLL showed dot-like or globular nuclear staining. Nuclear cyclin D1 protein can be detected in all cases of MCL and in rare cases of B-SLL/CLL using an immunohistochemical technique on formalin-fixed, paraffin-embedded tissue, and it does not appear to be detectable in reactive hyperplasias and other low-grade B-cell lymphomas. This protein may be useful in subclassification of low-grade B-cell lymphomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:7518196

  16. Intravascular large B-cell lymphoma of the kidney: A case report

    Directory of Open Access Journals (Sweden)

    Jia Nan

    2011-09-01

    Full Text Available Abstract We report a 41-year-old Chinese woman with intravascular large B-cell lymphoma diagnosed by percutaneous renal biopsy. The patient was admitted to Nanfang Hospital of Southern Medical University, Guangzhou, China with complaints of high spiking fever for a month and bilateral lower limb fatigue with difficulty ambulating for the past 5 months. She had renal dysfunction with a total urinary protein of 5.61 g/dL (56.1 g/L, serum albumin of 2.89 g/dL (28.9 g/L, urea nitrogen of 2.24 mg/dL (1.6 mmol/L, and serum creatinine of 0.54 mg/dL (48 μmol/L. Bone marrow biopsy revealed myeloproliferative disorder without abnormal myeloid or lymphocytic proliferation. Positron Emission Tomography-Computed Tomography (PET-CT showed marked bilateral swelling and enlargement of the renal parenchyma with splenic enlargement and involvement of multiple vertebrae. Percutaneous renal biopsy showed island-like accumulations of medium to large lymphoid cells in many areas of the interstitium, with round vesicular nuclei containing distinct basophilic nucleoli. Immunohistochemical analysis together with other supportive investigation confirmed the diagnosis of intravascular large B-cell lymphoma. Ten days later, she was started on chemotherapy with CHOP (cyclophosphamide, doxorubicin, leurocristime and prednisone for a week. Palliative radiotherapy DT 40Gy/20F with other supportive treatment was provided for metastatic foci in the medullary cavity of the sternum, T1-T7. The patient regained muscle strength in both lower limbs and was able to walk again after three weeks. The patient was discharged after hepatic and renal function and proteinuria values had returned to normal. Follow-up data shows the patient to be alive nine months after discharge.

  17. Quantitative image analysis in the assessment of diffuse large B-cell lymphoma.

    Science.gov (United States)

    Chabot-Richards, Devon S; Martin, David R; Myers, Orrin B; Czuchlewski, David R; Hunt, Kristin E

    2011-12-01

    Proliferation rates in diffuse large B-cell lymphoma have been associated with conflicting outcomes in the literature, more often with high proliferation associated with poor prognosis. In most studies, the proliferation rate was estimated by a pathologist using an immunohistochemical stain for the monoclonal antibody Ki-67. We hypothesized that a quantitative image analysis algorithm would give a more accurate estimate of the proliferation rate, leading to better associations with survival. In all, 84 cases of diffuse large B-cell lymphoma were selected according to the World Health Organization criteria. Ki-67 percentage positivity estimated by the pathologist was recorded from the original report. The same slides were then scanned using an Aperio ImageScope, and Ki-67 percentage positivity was calculated using a computer-based quantitative immunohistochemistry nuclear algorithm. In addition, chart review was performed and survival time was recorded. The Ki-67 percentage estimated by the pathologist from the original report versus quantitative image analysis was significantly correlated (Pquantitative image analysis (P=0.021). There was less agreement at lower Ki-67 percentages. Comparison of Ki-67 percentage positivity versus survival did not show significant association either with pathologist estimate or quantitative image analysis. However, although not significant, there was a trend of worse survival at higher proliferation rates detected by the pathologist but not by quantitative image analysis. Interestingly, our data suggest that the Ki-67 percentage positivity as assessed by the pathologist may be more closely associated with survival outcome than that identified by quantitative image analysis. This may indicate that pathologists are better at selecting appropriate areas of the slide. More cases are needed to assess whether this finding would be statistically significant. Due to the good correlation between pathologist estimate and quantitative image

  18. Myelodysplastic Syndrome with Myelofibrosis Transformed to a Precursor B-Cell Acute Lymphoblastic Leukemia: A Case Report with Review of the Literature

    OpenAIRE

    2012-01-01

    Myelodysplastic syndromes (MDS) comprise a group of heterogeneous clonal hematopoietic cell disorders characterized by cytopenias, bone marrow hypercellularity, and increased risk of transformation to acute leukemias. MDS usually transformed to acute myeloid leukemia, and transformation to acute lymphoblastic leukemia (ALL) is rare. Herein, we report a unique patient who presented with MDS with myelofibrosis. Two months after the initial diagnosis, she progressed to a precursor B-cell acute l...

  19. Pathogenetic, Clinical, and Prognostic Features of Adult t(4;11)(q21;q23)/MLL-AF4 Positive B-Cell Acute Lymphoblastic Leukemia

    OpenAIRE

    Marchesi, F.; Girardi, K.; Avvisati, G.

    2011-01-01

    Translocation t(4;11)(q21;q23) leading to formation of MLL-AF4 fusion gene is found in about 10% of newly diagnosed B-cell acute lymphoblastic leukemia (ALL) in adult patients. Patients expressing this chromosomal aberration present typical biological, immunophenotypic, and clinical features. This form of leukemia is universally recognized as high-risk leukemia and treatment intensification with allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR) could b...

  20. Mutation mismatch repair gene deletions in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Couronné, Lucile; Ruminy, Philippe; Waultier-Rascalou, Agathe; Rainville, Vinciane; Cornic, Marie; Picquenot, Jean-Michel; Figeac, Martin; Bastard, Christian; Tilly, Hervé; Jardin, Fabrice

    2013-05-01

    To further unravel the molecular pathogenesis of diffuse large B-cell lymphoma (DLBCL), we performed high-resolution comparative genomic hybridization on lymph node biopsies from 70 patients. With this strategy, we identified microdeletions of genes involved in the mutation mismatch repair (MMR) pathway in two samples. The first patient presented with a homozygous deletion of MSH2-MSH6 due to duplication of an unbalanced pericentric inversion of chromosome 2. The other case showed a PMS2 heterozygous deletion. PMS2 and MSH2-MSH6 abnormalities, respectively, resulted in a decrease and complete loss of gene expression. However, unlike tumors associated with the hereditary non-polyposis colorectal cancer syndrome or immunodeficiency-related lymphomas, no microsatellite instability was detected. Mutational profiles revealed especially in one patient an aberrant hypermutation without a clear activation-induced cytidine deaminase signature, indicating a breakdown of the high-fidelity repair in favor of the error-prone repair pathway. Our findings suggest that in a rare subset of patients, inactivation of the genes of the MMR pathway is likely an important step in the molecular pathogenesis of DLBCL and does not involve the same molecular mechanisms as other common neoplasms with MMR deficiency.

  1. Piperlongumine inhibits the proliferation and survival of B-cell acute lymphoblastic leukemia cell lines irrespective of glucocorticoid resistance

    Energy Technology Data Exchange (ETDEWEB)

    Han, Seong-Su, E-mail: seong-su-han@uiowa.edu [Division of Pediatric Hematology-Oncology, University of Iowa Carver College of Medicine, Iowa City, IA (United States); Han, Sangwoo [Health and Human Physiology, University of Iowa Carver College of Medicine, Iowa City, IA (United States); Kamberos, Natalie L. [Division of Pediatric Hematology-Oncology, University of Iowa Carver College of Medicine, Iowa City, IA (United States)

    2014-09-26

    Highlights: • PL inhibits the proliferation of B-ALL cell lines irrespective of GC-resistance. • PL selectively kills B-ALL cells by increasing ROS, but not normal counterpart. • PL does not sensitize majority of B-ALL cells to DEX. • PL represses the network of constitutively activated TFs and modulates their target genes. • PL may serve as a new therapeutic molecule for GC-resistant B-ALL. - Abstract: Piperlongumine (PL), a pepper plant alkaloid from Piper longum, has anti-inflammatory and anti-cancer properties. PL selectively kills both solid and hematologic cancer cells, but not normal counterparts. Here we evaluated the effect of PL on the proliferation and survival of B-cell acute lymphoblastic leukemia (B-ALL), including glucocorticoid (GC)-resistant B-ALL. Regardless of GC-resistance, PL inhibited the proliferation of all B-ALL cell lines, but not normal B cells, in a dose- and time-dependent manner and induced apoptosis via elevation of ROS. Interestingly, PL did not sensitize most of B-ALL cell lines to dexamethasone (DEX). Only UoC-B1 exhibited a weak synergistic effect between PL and DEX. All B-ALL cell lines tested exhibited constitutive activation of multiple transcription factors (TFs), including AP-1, MYC, NF-κB, SP1, STAT1, STAT3, STAT6 and YY1. Treatment of the B-ALL cells with PL significantly downregulated these TFs and modulated their target genes. While activation of AURKB, BIRC5, E2F1, and MYB mRNA levels were significantly downregulated by PL, but SOX4 and XBP levels were increased by PL. Intriguingly, PL also increased the expression of p21 in B-ALL cells through a p53-independent mechanism. Given that these TFs and their target genes play critical roles in a variety of hematological malignancies, our findings provide a strong preclinical rationale for considering PL as a new therapeutic agent for the treatment of B-cell malignancies, including B-ALL and GC-resistant B-ALL.

  2. Construction and analysis of tree models for chromosomal classification of diffuse large B-cell lymphomas

    Institute of Scientific and Technical Information of China (English)

    Hui-Yong Jiang; Zhong-Xi Huang; Xue-Feng Zhang; Richard Desper; Tong Zhao

    2007-01-01

    AIM: To construct tree models for classification of diffuse large B-cell lymphomas (DLBCL) by chromosome copy numbers, to compare them with cDNA microarray classification, and to explore models of multi-gene, multi-step and multi-pathway processes of DLBCL tumorigenesis.METHODS: Maximum-weight branching and distance based models were constructed based on the comparative genomic hybridization (CGH) data of 123 DLBCL samples using the established methods and software of Desper et al. A maximum likelihood tree model was also used to analyze the data. By comparing with the results reported in literature, values of tree models in the classification of DLBCL were elucidated.RESULTS: Both the branching and the distance-based trees classified DLBCL into three groups. We combined the classification methods of the two models and classified DLBCL into three categories according to their characteristics. The first group was marked by +Xq, +Xp, -17p and +13q; the second group by +3q, +18q and +18p; and the third group was marked by -6q and +6p. This chromosomal classification was consistent with cDNA classification. It indicated that -6q and +3q were two main events in the tumorigenesis of lymphoma.CONCLUSION: Tree models of lymphoma established from CGH data can be used in the classification of DLBCL. These models can suggest multi-gene, multi-step and multi-pathway processes of tumorigenesis.Two pathways, -6q preceding +6q and +3q preceding +18q, may be important in understanding tumorigenesis of DLBCL. The pathway, -6q preceding +6q, may have a close relationship with the tumorigenesis of non-GCB DLBCL.

  3. Low GILT expression is associated with poor patient survival in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Hannah ePhipps-Yonas

    2013-12-01

    Full Text Available The MHC class II-restricted antigen processing pathway presents antigenic peptides acquired in the endocytic route for the activation of CD4+ T cells. Multiple cancers express MHC class II, which may influence the anti-tumor immune response and patient outcome. Low MHC class II expression is associated with poor survival in diffuse large B-cell lymphoma (DLBCL, the most common form of aggressive non-Hodgkin lymphoma. Therefore, we investigated whether gamma-interferon-inducible lysosomal thiol reductase (GILT, an upstream component of the MHC class II-restricted antigen processing pathway that is not regulated by the transcription factor class II transactivator, may be important in DLBCL biology. GILT reduces protein disulfide bonds in the endocytic compartment, exposing additional epitopes for MHC class II binding and facilitating antigen presentation. In each of four independent gene expression profiling cohorts with a total of 585 DLBCL patients, low GILT expression was significantly associated with poor overall survival. In contrast, low expression of a classical MHC class II gene, HLA-DRA, was associated with poor survival in one of four cohorts. The association of low GILT expression with poor survival was independent of established clinical and molecular prognostic factors, the International Prognostic Index and the cell of origin classification, respectively. Immunohistochemical analysis of GILT expression in 96 DLBCL cases demonstrated variation in GILT protein expression within tumor cells which correlated strongly with GILT mRNA expression. These studies identify a novel association between GILT expression and clinical outcome in lymphoma. Our findings underscore the role of antigen processing in DLBCL and suggest that molecules targeting this pathway warrant investigation as potential therapeutics.

  4. Anemia in diffuse large B-cell non-Hodgkin lymphoma: the role of interleukin-6, hepcidin and erythropoietin

    NARCIS (Netherlands)

    Tisi, M.C.; Bozzoli, V.; Giachelia, M.; Massini, G.; Ricerca, B.M.; Maiolo, E.; D'Alo, F.; Larocca, L.M.; Piciocchi, A.; Tjalsma, H.; Swinkels, D.W.; Voso, M.T.; Leone, G.; Hohaus, S.

    2014-01-01

    Anemia is a frequent sign in patients with diffuse large B-cell lymphoma (DLBCL) at diagnosis. We determined erythropoietin, hepcidin and interleukin-6 (IL-6) in plasma samples of 53 patients with DLBCL. The majority of patients (40/53, 75%) showed defective endogenous erythropoietin production, in

  5. Prognostic value of anemia and C-reactive protein levels in diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Adams, Hugo J A; De Klerk, John M H; Fijnheer, Rob; Heggelman, Ben G F; Dubois, Stefan V.; Nievelstein, Rutger A J; Kwee, Thomas C.

    2015-01-01

    Purpose To determine the prognostic value of pretreatment anemia, pretreatment elevated C-reactive protein (CRP) levels, and 6-month posttreatment anemia in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin, and

  6. Mutational and structural analysis of diffuse large B-cell lymphoma using whole genome sequencing | Office of Cancer Genomics

    Science.gov (United States)

    Abstract: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer comprising at least two molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease.

  7. Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Young, Ken H; Leroy, Karen; Møller, Michael Boe;

    2008-01-01

    The purpose of this study is to correlate the presence of TP53 gene mutations with the clinical outcome of a cohort of patients with diffuse large B-cell lymphoma (DLBCL) assembled from 12 medical centers. TP53 mutations were identified in 102 of 477 patients and the overall survival (OS) of pati...

  8. EANM procedure guideline for radio-immunotherapy for B-cell lymphoma with Y-90-radiolabelled ibritumomab tiuxetan (Zevalin)

    NARCIS (Netherlands)

    Tennvall, Jan; Fischer, Manfred; Delaloye, Angelika Bischof; Bombardieri, Emilio; Bodei, Lisa; Giammarile, Francesco; Lassmann, Michael; Oyen, Wim; Brans, Boudewijn

    2007-01-01

    Background In January 2004, EMEA approved Y-90-radiolabelled ibritumomab tiuxetan, Zevalin, in Europe for the treatment of adult patients with rituximab-relapsed or -refractory CD20+ follicular B-cell non-Hodgkin's lymphoma. The number of European nuclear medicine departments using Zevalin is contin

  9. Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Kramer, M.H.H.; Hermans, J; Wijburg, E; Philippo, K; Geelen, E; van Krieken, J.H.J.M.; de Jong, D; Maartense, E; Schuuring, E; Kluin, P M

    1998-01-01

    Diffuse large B-cell lymphoma (DLCL) is characterized by a marked degree of morphologic and clinical heterogeneity. We studied 156 patients with de novo DLCL for rearrangements of the BCL2, BCL6, and MYC oncogenes by Southern blot analysis and BCL2 protein expression. We related these data to the pr

  10. Immunohistochemical profiling of caspase signaling pathways predicts clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas.

    NARCIS (Netherlands)

    Muris, J.J.; Cillessen, S.A.; Vos, W.; Houdt, I.S. van; Kummer, J.A.; Krieken, J.H.J.M. van; Jiwa, N.M.; Jansen, P.A.M.; Kluin-Nelemans, H.C.; Ossenkoppele, G.J.; Gundy, C.; Meijer, C.J.M.; Oudejans, J.J.

    2005-01-01

    We used biopsy specimens of primary nodal diffuse large B-cell lymphoma (DLBCL) to investigate whether the inhibition of caspase 8 and/or 9 apoptosis signaling pathways predicts clinical outcome. Expression levels of cellular FLICE inhibitory protein (c-Flip) and numbers of active caspase 3-positive

  11. Immunohistochemical profiling of caspase signaling pathways predicts clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas

    NARCIS (Netherlands)

    Muris, JJF; Cillessen, SAGM; Vos, W; van Houdt, IS; Kummer, JA; van Krieken, JHJM; Jiwa, NM; Jansen, PM; Kluin-Nelemans, HC; Ossenkoppele, GJ; Gundy, C; Meijer, CJLM; Oudejans, JJ

    2005-01-01

    We used biopsy specimens of primary nodal diffuse large B-cell lymphoma (DLBCL) to investigate whether the inhibition of caspase 8 and/or 9 apoplosis signaling pathways predicts clinical outcome. Expression levels of cellular FLICE inhibitory protein (c-Flip) and numbers of active caspase 3-positive

  12. Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

    DEFF Research Database (Denmark)

    Tzankov, Alexandar; Xu-Monette, Zijun Y; Gerhard, Marc;

    2014-01-01

    In order to address the debatable prognostic role of MYC rearrangements in diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements by fluorescence in situ hybridization in 563 cases using br...

  13. Identification of residual leukemic cells by flow cytometry in childhood B-cell precursor acute lymphoblastic leukemia: verification of leukemic state by flow-sorting and molecular/cytogenetic methods

    OpenAIRE

    2012-01-01

    Reduction in minimal residual disease, measured by real-time quantitative PCR or flow cytometry, predicts prognosis in childhood B-cell precursor acute lymphoblastic leukemia. We explored whether cells reported as minimal residual disease by flow cytometry represent the malignant clone harboring clone-specific genomic markers (53 follow-up bone marrow samples from 28 children with B-cell precursor acute lymphoblastic leukemia). Cell populations (presumed leukemic and non-leukemic) were flow-s...

  14. Enhancer mutations of Akv murine leukemia virus inhibit the induction of mature B-cell lymphomas and shift disease specificity towards the more differentiated plasma cell stage

    DEFF Research Database (Denmark)

    Sørensen, Karina Dalsgaard; Kunder, Sandra; Quintanilla-Martinez, Leticia;

    2007-01-01

    This study investigates the role of the proviral transcriptional enhancer for B-lymphoma induction by exogenous Akv murine leukemia virus. Infection of newborn inbred NMRI mice with Akv induced 35% plasma cell proliferations (PCPs) (consistent with plasmacytoma), 33% diffuse large B-cell lymphomas...... showed that many of the tumors/cell proliferations induced by each virus were polyclonal. Our results indicate that enhancer mutations weaken the ability of Akv to induce mature B-cell lymphomas prior to the plasma cell stage, whereas development of plasma cell proliferations is less dependent of viral......, 25% follicular B-cell lymphomas and few splenic marginal zone and small B-cell lymphomas. Deleting one copy of the 99-bp proviral enhancer sequence still allowed induction of multiple B-cell tumor types, although PCPs dominated (77%). Additional mutation of binding sites for the glucocorticoid...

  15. Clinical and biological aspects of aggressive B-cell non-Hodgkin lymphoma in adolescents and young adults

    Directory of Open Access Journals (Sweden)

    Coso D

    2015-11-01

    Full Text Available Diane Coso, Sylvain Garciaz, Réda BouabdallahDepartment of Hematology, Cancer Center Institut J. Paoli-I. Calmettes, University of La Méditerranée, Marseille, FranceAbstract: Non-Hodgkin lymphomas (NHLs are one of the most frequent malignancies in adolescents and young adults (AYA. Among NHLs, Burkitt's lymphoma (BL represents approximately 40% while diffuse large B-cell lymphoma (DLBCL accounts for nearly 20% of cases. Primary mediastinal B-cell lymphoma is a variant of DLBCL, which preferentially concerns young patients. Biology of B-NHLs is well known and several pathways involving chromosomal translocations, gene rearrangements, and molecular profiling are the subject of continuous investigations. AYA with B-NHL have inferior survival when compared with children. The reasons for this unfavorable outcome are multifactorial, but disease-related biological characteristics of the tumor represent a powerful factor influencing survival. The choice of optimal strategy in the management of B-NHL in patients of 15–29 years old remains controversial and depends on the treating institution and its physicians. Although children and younger adolescents benefit from pediatric approaches using intensive treatment, older adolescents are often treated with adult rituximab-based chemotherapy. In this review, we focus on the current knowledge relevant to AYA with DLBCL and primary mediastinal B-cell lymphoma.Keywords: DLBCL, PMBCL, AYA, prognosis, treatment

  16. MYC protein expression in primary diffuse large B-cell lymphoma of the central nervous system.

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    Kamraan Z Gill

    Full Text Available Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL is a rare, aggressive subtype of DLBCL, the biology of which is poorly understood. Recent studies have suggested a prognostic role of MYC protein expression in systemic DLBCL, but little is known about the frequency and significance of MYC protein expression in CNS DLBCL. Hence, we investigated MYC protein expression profiles of CNS DLBCL and assessed the relationship between MYC expression and a variety of histopathologic, immunophenotypic, genetic, and clinical features. Fifty-nine CNS DLBCL diagnosed at our institution over the past 13 years were evaluated. The majority of cases (80% showed centroblastic morphology, and 12 (20% displayed a perivascular pattern of infiltration. According to the Hans criteria, 41 (69% cases had a non-germinal center B-cell and 18 (31% had a germinal center B-cell cell-of-origin (COO phenotype. Mean MYC protein expression was 50% (median: 50%, range: 10-80%. Forty-three cases (73% showed MYC overexpression (≥ 40%, and 35 (60% showed MYC/BCL2 coexpression. MYC overexpression was seen in the single case harboring MYC translocation and in the cases showing increased copies of MYC (27%; however, no significant difference in mean MYC expression was seen between groups harboring or lacking MYC aberrations. In our series, age was associated with a significantly increased risk of death, and the perivascular pattern of infiltration was associated with a significantly increased risk of disease progression. Neither MYC expression (with or without BCL2 coexpression nor other variables, including COO subtype were predictive of clinical outcome. Our findings indicate that the proportion of CNS DLBCL overexpressing MYC is higher compared to systemic DLBCL, and MYC overexpression appears to be independent of genetic MYC abnormalities. Thus, MYC expression and other immunophenotypic markers used for prognostication of systemic DLBCL might not apply

  17. Targetable activating mutations are very frequent in GCB and ABC diffuse large B-cell lymphoma.

    Science.gov (United States)

    Bohers, Elodie; Mareschal, Sylvain; Bouzelfen, Abdelilah; Marchand, Vinciane; Ruminy, Philippe; Maingonnat, Catherine; Ménard, Anne-Lise; Etancelin, Pascaline; Bertrand, Philippe; Dubois, Sydney; Alcantara, Marion; Bastard, Christian; Tilly, Hervé; Jardin, Fabrice

    2014-02-01

    Diffuse large B cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy that can be divided in two major subgroups, germinal center B-cell-like (GCB) and activated B-cell-like (ABC). Activating mutations of genes involved in the BCR and NF-κB pathways (CD79A, CD79B, MYD88, and CARD11) or in epigenetic regulation (EZH2) have been recently reported, preferentially in one of the two DLBCL subtypes. We analyzed the mutational status of these five recurrently mutated genes in a cohort of 161 untreated de novo DLBCL. Overall, 93 mutations were detected, in 61 (38%) of the patients. The L265P MYD88 mutation was the most frequent MYD88 variant (n = 18), observed exclusively in the ABC subtype. CD79A/CD79B ITAM domains were targeted in ABC DLBCL (12/77; 16%), whereas CARD11 mutations were equally distributed in the two subtypes. The EZH2 Y641 substitution was found almost exclusively in the GCB subgroup (15/62; 24%). Twenty cases (12%) displayed two activating mutations, including the most frequent CD79/MYD88 variants combination (n = 8) which is observed exclusively in the ABC subtype. When considering only ABC DLBCL patients treated by rituximab plus chemotherapy, the presence of an activating NF-κB mutation was associated with an unfavorable outcome (3-years OS 26% for mutated cases versus 67% for the cases without mutations, P = 0.0337). Our study demonstrates that activating and targetable mutations are observed at a very high frequency in DLBCL at the time of diagnosis, indicating that sequencing of a limited number of genes could help tailor an optimal treatment strategy in DLBCL.

  18. B-cell prolymphocytic leukemia: a specific subgroup of mantle cell lymphoma.

    Science.gov (United States)

    van der Velden, Vincent H J; Hoogeveen, Patricia G; de Ridder, Dick; Schindler-van der Struijk, Magdalena; van Zelm, Menno C; Sanders, Mathijs; Karsch, Dennis; Beverloo, H Berna; Lam, King; Orfao, Alberto; Lugtenburg, Pieternella J; Böttcher, Sebastian; van Dongen, Jacques J M; Langerak, Anton W; Kappers-Klunne, Mies; van Lom, Kirsten

    2014-07-17

    B-cell prolymphocytic leukemia (B-PLL) is a rare mature B-cell malignancy that may be hard to distinguish from mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). B-PLL cases with a t(11;14) were redefined as MCL in the World Health Organization 2008 classification. We evaluated 13 B-PLL patients [7 being t(11;14)-positive (B-PLL+) and 6 negative (B-PLL-)] and compared them with MCL and CLL patients. EuroFlow-based immunophenotyping showed significant overlap between B-PLL+ and B-PLL-, as well as between B-PLL and MCL, whereas CLL clustered separately. Immunogenotyping showed specific IGHV gene usage partly resembling MCL. Gene expression profiling showed no separation between B-PLL+ and B-PLL- but identified 3 subgroups. One B-PLL subgroup clustered close to CLL and another subgroup clustered with leukemic MCL; both were associated with prolonged survival. A third subgroup clustered close to nodal MCL and was associated with short survival. Gene expression profiles of both B-PLL+ and B-PLL- showed best resemblance with normal immunoglobulin M-only B-cells. Our data confirm that B-PLL+ is highly comparable to MCL, indicate that B-PLL- also may be considered as a specific subgroup of MCL, and suggest that B-PLL is part of a spectrum, ranging from CLL-like B-PLL, to leukemic MCL-like B-PLL, to nodal MCL-like B-PLL.

  19. Next generation sequencing and the management of diffuse large B-cell lymphoma: from whole exome analysis to targeted therapy.

    Science.gov (United States)

    Jardin, Fabrice

    2014-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma, accounting for 30-40% of newly diagnosed non-Hodgkin lymphomas. Historically, DLBCL has been thought to involve recurrent translocations of the IGH gene and the deregulation of rearranged oncogenes. Recent advances in next generation sequencing (NGS) have provided a vast and comprehensive catalogue of cancer genes involved in DLBCL pathogenesis. Whole exome sequencing (WES) of more than two hundred DLBCLs has completely redefined the genetic landscape of the disease by identifying recurrent single nucleotide variants and providing new therapeutic opportunities for the germinal center B-cell like (GCB), activated B-cell like (ABC), or primary mediastinal B-cell (PMBL) molecular subtypes. Some of these somatic mutations target genes that play a crucial role in B-cell function (BCR signaling, NF-κB pathway, NOTCH signaling, Toll-like receptor signaling, and the PI3K pathway), immunity, cell cycle/apoptosis, or chromatin modification. In this review, we present an overview of the mutations recently discovered by NGS in DLBCL and discuss their biological relevance and possible impacts on clinical management.

  20. Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

    Science.gov (United States)

    2015-10-30

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

  1. Chronic Inflammation-Related Diffuse Large B-Cell Lymphoma Around the Area of Thoracotomy After Decortication

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    Bayram Metin

    2014-06-01

    Full Text Available Chest wall tumors consist 5% of all tumors in the thorax. Lymphomas compose of less than 5% of all primary chest wall malignancy.Sixty three years old patient who had an operation for pleural thickness two years ago admitted with complaint of left-sided chest pain.Following the detection of mass lesion radiologically at the place of previous operation area, the patient was operated based on needle biopsy result suggesting Ewing /PNET or pulmonary originated tumor. After the operation, pathological examination confirmed chronic inflammation-related diffuse large B-cell lymphoma. Since it has been rarely reported in the literature, we aimed to present the case of chronic inflammation-related diffuse large B-cell lymphoma developed within such a short time as two years on the ground of surgical incision scar tissue together with our radiologic, surgical, and pathological findings.

  2. Isolated sciatic neuropathy as an initial manifestation of a high grade B-cell lymphoma: A case report and literature review.

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    He, Wenzhuan; Wang, Weizhen; Gustas, Cristy; Malysz, Jozef; Kaur, Divpreet

    2016-10-01

    Sciatic nerve neuropathy due to infiltrating of a high grade B-cell lymphoma is a very rare situation and has not often been reported. We report a case with a previous history of indolent lymphoma who presented with isolated sciatic nerve neuropathy and was found to have diffuse large B cell lymphoma involving the sciatic nerve. Although the current case is not a primary sciatic nerve lymphoma given the systematic involvement shown on MRI and PET/CT scan, the case represents a neurolymphomatosis of the sciatic nerve given the direct invasion of the lymphoma cells into the sciatic nerve. Due to the rarity of this condition, we subsequently reviewed related literatures.

  3. CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature

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    Hu, Shimin; Xu-Monette, Zijun Y; Balasubramanyam, Aarthi;

    2013-01-01

    CD30, originally identified as a cell-surface marker of Reed-Sternberg and Hodgkin cells of classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including a subset of diffuse large B-cell lymphoma (DLBCL). However, the prognostic and biological importance of CD3...

  4. Diffuse large B-cell lymphoma of the parotid gland: Cytological, histopathological, and immunohistochemical features: A rare case report

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    Sainath K Andola

    2016-01-01

    Full Text Available Primary malignant lymphomas of the salivary glands are rare, accounting for 2-5% of salivary gland tumors and 5% of extranodal lymphomas, frequently seen in the parotid gland. There are single case reports mentioned in the literature. Clinical presentation is not characteristic and the disease is often overlooked with delay in diagnosis and treatment. We are reporting a case of bilateral parotid gland lymphoma in a 55-year-old male, presented with bilateral enlarged parotids. Magnetic resonance imaging (MRI showed bilateral enlarged parotid glands with multiple well-defined intraparotid lesions. Fine Needle Aspiration Cytology (FNAC of both showed mixed population of lymphoid cells with large monocytoid cells with scant cytoplasm, anisonucleosis with prominent nucleoli, and numerous mitoses suggestive of non-Hodgkin's lymphoma (NHL. Histopathology showed sheets of large lymphoma cells destructing the salivary acini and infiltrating the periparotid fat. Immunohistochemistry (IHC showed diffuse CD20 positivity, B-cell lymphoma 6 protein (Bcl-6 was focally positive and negative for cluster of differentiation (CD 3, CD5, CD10, and Multiple myeloma oncogene-1 (MUM1 which led to the diagnosis of NHL-Diffuse large B cell type.

  5. Insights into the Molecular Pathogenesis of Activated B-Cell-like Diffuse Large B-Cell Lymphoma and Its Therapeutic Implications

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    Lenz, Georg [Translational Oncology, Department of Medicine A, Albert-Schweitzer Campus 1, University Hospital Münster, 48149 Münster (Germany); Cluster of Excellence EXC 1003, Cells in Motion, 48149 Münster (Germany)

    2015-05-22

    Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL) has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC) DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients.

  6. Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group

    Science.gov (United States)

    Labar, Boris; Suciu, Stefan; Willemze, Roel; Muus, Petra; Marie, Jean-Pierre; Fillet, Georges; Berneman, Zwi; Jaksic, Branimir; Feremans, Walter; Bron, Dominique; Sinnige, Harm; Mistrik, Martin; Vreugdenhil, Gerard; De Bock, Robrecht; Nemet, Damir; Gilotay, Caroline; Amadori, Sergio; de Witte, Theo

    2010-01-01

    Background Corticosteroids are a standard component of the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Our aim was to determine whether dexamethasone results in a better outcome than prednisolone. Design and Methods Adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma were randomized to receive, as part of their induction therapy on days 1–8 and 15–22, either dexamethasone 8 mg/m2 or prednisolone 60 mg/m2. Those who reached complete remission were given two courses of consolidation therapy with high-dose cytarabine and mitoxantrone and methotrexate and asparaginase. Subsequently patients younger than 50 years, with a suitable donor, were to undergo allogeneic stem cell transplantation, whereas the others were planned to receive either an autologous stem cell transplant or high-dose maintenance chemotherapy with prophylactic central nervous system irradiation. Randomization was done with a minimization technique. The primary endpoint was event-free survival and the analyses was conducted on an intention-to-treat basis. Results Between August 1995 and October 2003, 325 patients between 15 to 72 years of age were randomized to receive either dexamethasone (163 patients) or prednisolone (162 patients). After induction and the course of first consolidation therapy, 131 (80.4%) patients in the dexamethasone group and 124 (76.5%) in the prednisolone group achieved complete remission. No significant difference was observed between the two treatment groups with regards to 6-year event-free survival rates (±SE) which were 25.9% (3.6%) and 28.7% (3.5%) in the dexamethasone and prednisolone groups, respectively (P=0.82, hazard ratio 0.97; 95% confidence interval, 0.75–1.25). Disease-free survival after complete remission was also similar in the dexamethasone and prednisolone groups, the 6-year rates being 32.3% and 37.5%, respectively (hazard ratio 1.03; 95% confidence interval 0.76–1.40). The 6-year cumulative

  7. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia.

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    Sanjuan-Pla, Alejandra; Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W; Marschalek, Rolf; Menéndez, Pablo

    2015-12-17

    Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a "multiple-and-sequential-hit" model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one "big-hit" might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models.

  8. Inactivating Mutations in GNA13 and RHOA in Burkitt’s Lymphoma and Diffuse Large B cell Lymphoma: A Tumor Suppressor Function for the Gα13/RhoA Axis in B Cells

    Science.gov (United States)

    O’Hayre, Morgan; Inoue, Asuka; Kufareva, Irina; Wang, Zhiyong; Mikelis, Constantinos M.; Drummond, Rebecca A.; Avino, Silvia; Finkel, Kira; Kalim, Khalid; DiPasquale, Giovanni; Guo, Fukun; Aoki, Junken; Zheng, Yi; Lionakis, Michail S.; Molinolo, Alfredo A.; Gutkind, J. Silvio

    2015-01-01

    G-proteins and their cognate G-protein coupled receptors (GPCRs) function as critical signal transduction molecules that regulate cell survival, proliferation, motility and differentiation. The aberrant expression and/or function of these molecules have been linked to the growth, progression and metastasis of various cancers. As such, the analysis of mutations in the genes encoding GPCRs, G-proteins and their downstream targets provides important clues regarding how these signaling cascades contribute to malignancy. Recent genome-wide sequencing efforts have unveiled the presence of frequent mutations in GNA13, the gene encoding the G-protein Gα13, in Burkitt’s lymphoma and Diffuse Large B cell lymphoma (DLBCL). We found that mutations in the downstream target of Gα13, RhoA, are also present in Burkitt’s lymphoma and DLBCL. By multiple complementary approaches, we now show that that these cancer-specific GNA13 and RHOA mutations are inhibitory in nature, and that the expression of wild type Gα13 in B cell lymphoma cells with mutant GNA13 has limited impact in vitro but results in a remarkable growth inhibition in vivo. Thus, although Gα13 and RhoA activity has previously been linked to cellular transformation and metastatic potential of epithelial cancers, our findings support a tumor suppressive role for Gα13 and RhoA in Burkitt’s lymphoma and DLBCL. PMID:26616858

  9. Case Report of Diffuse Large B Cell Lymphoma of Uterine Cervix Treated at a Semiurban Cancer Centre in North India

    Science.gov (United States)

    Sridhar, Epari

    2016-01-01

    Lymphoma of the uterine cervix is very rare. We report a case of diffuse large B cell lymphoma (DLBCL) involving the uterine cervix treated at a newly commissioned semiurban cancer centre in north India in 2015. Data for this study was obtained from the hospital electronic medical records and the patient's case file. We also reviewed published case reports of uterine and cervical lymphoma involving forty-one patients. We treated a case of stage IV DLBCL cervix with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) and intrathecal methotrexate followed by consolidation with radiotherapy. The patient showed complete response to chemotherapy. We conclude that, in advanced stage lymphoma involving uterus and cervix, combination of chemotherapy and radiotherapy is effective in short term. PMID:27597906

  10. Case Report of Diffuse Large B Cell Lymphoma of Uterine Cervix Treated at a Semiurban Cancer Centre in North India

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    Vibhor Sharma

    2016-01-01

    Full Text Available Lymphoma of the uterine cervix is very rare. We report a case of diffuse large B cell lymphoma (DLBCL involving the uterine cervix treated at a newly commissioned semiurban cancer centre in north India in 2015. Data for this study was obtained from the hospital electronic medical records and the patient’s case file. We also reviewed published case reports of uterine and cervical lymphoma involving forty-one patients. We treated a case of stage IV DLBCL cervix with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and intrathecal methotrexate followed by consolidation with radiotherapy. The patient showed complete response to chemotherapy. We conclude that, in advanced stage lymphoma involving uterus and cervix, combination of chemotherapy and radiotherapy is effective in short term.

  11. Molecular subtyping of diffuse large B-cell lymphoma: update on biology, diagnosis and emerging platforms for practising pathologists.

    Science.gov (United States)

    Gifford, Grace K; Gill, Anthony J; Stevenson, William S

    2016-01-01

    Molecular classification of diffuse large B-cell lymphoma (DLBCL) is critical. Numerous methodologies have demonstrated that DLBCL is biologically heterogeneous despite morphological similarities. This underlies the disparate outcomes of treatment response or failure in this common non-Hodgkin lymphoma. This review will summarise historical approaches to lymphoma classifications, current diagnosis of DLBCL, molecular techniques that have primarily been used in the research setting to distinguish and subclassify DLBCL, evaluate contemporary diagnostic methodologies that seek to translate lymphoma biology into clinical practice, and introduce novel diagnostic platforms that may overcome current issues. The review concludes with an overview of key molecular lesions currently identified in DLBCL, all of which are potential targets for drug treatments that may improve survival and cure.

  12. Primary diffuse large B-cell lymphoma of the prostate: A report of two cases with diagnostic considerations

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    Aanchal Kakkar

    2015-01-01

    Full Text Available Primary prostatic lymphomas are extremely unusual neoplasms. Their rarity and nonspecific symptomatology at presentation usually prompt a clinical diagnosis of benign prostatic hyperplasia or chronic prostatitis, leading to significant delay in diagnosis. Clinical examination, serum prostate-specific antigen levels, and transrectal ultrasonography (TRUS are not of much utility in differential diagnosis, and histological examination is the gold standard. We report two cases of primary non-Hodgkin lymphoma of prostate, diffuse large B-cell type, diagnosed on TRUS-guided prostatic biopsies. Correct diagnosis is of crucial importance as the therapeutic strategy for lymphoma is radically different from that for carcinoma, and early detection of prostatic lymphoma can be potentially curative. Thus, knowledge of this rare entity, inclusion in differential diagnosis of lower urinary tract obstruction, and application of an appropriate immunohistochemical panel are essential so as not to miss this unusual diagnosis and to avoid unnecessary surgery.

  13. Targeting malignant B cells as antigen-presenting cells: TLR-9 agonist induces systemic regression of lymphoma.

    Science.gov (United States)

    Klein-González, Nela; Holtick, Udo; Fairfax, Kirsten; Weihrauch, Martin R; von Bergwelt-Baildon, Michael S

    2011-03-01

    Evaluation of: Brody JD, Ai WZ, Czerwinski DK et al. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a Phase I/II study. J. Clin. Oncol. 28(28), 4324-4332 (2010). Despite high response rates of the follicular B-cell lymphoma to monoclonal antibodies, the clinical course of lymphoma is still characterized by a continuous pattern of relapse. Brody and colleagues treated 15 patients with relapsed, low-grade lymphoma using low-dose radiotherapy applied to one of the tumor sites with combined injection of a TLR-9 agonist at the same site. This strategy induced specific immunity and tumor regression in several patients with an objective response rate of 27%. The results indicate an involvement of the tumor TLR-9-expressing B cells acting as antigen-presenting cells. TLR-9 in situ vaccination combined with local radiotherapy clearly warrants further in-depth analysis and investigation in a Phase III randomized trial, and may provide a new opportunity for the treatment of B-cell malignancies.

  14. Immunohistochemical and molecular characteristics with prognostic significance in diffuse large B-cell lymphoma.

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    Carmen Bellas

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. We analyzed 100 cases of DLBCL to evaluate the prognostic value of immunohistochemical markers derived from the gene expression profiling-defined cell origin signature, including MYC, BCL2, BCL6, and FOXP1 protein expression. We also investigated genetic alterations in BCL2, BCL6, MYC and FOXP1 using fluorescence in situ hybridization and assessed their prognostic significance. BCL6 rearrangements were detected in 29% of cases, and BCL6 gene alteration (rearrangement and/or amplification was associated with the non-germinal center B subtype (non-GCB. BCL2 translocation was associated with the GCB phenotype, and BCL2 protein expression was associated with the translocation and/or amplification of 18q21. MYC rearrangements were detected in 15% of cases, and MYC protein expression was observed in 29% of cases. FOXP1 expression, mainly of the non-GCB subtype, was demonstrated in 37% of cases. Co-expression of the MYC and BCL2 proteins, with non-GCB subtype predominance, was observed in 21% of cases. We detected an association between high FOXP1 expression and a high proliferation rate as well as a significant positive correlation between MYC overexpression and FOXP1 overexpression. MYC, BCL2 and FOXP1 expression were significant predictors of overall survival. The co-expression of MYC and BCL2 confers a poorer clinical outcome than MYC or BCL2 expression alone, whereas cases negative for both markers had the best outcomes. Our study confirms that DLBCL, characterized by the co-expression of MYC and BCL2 proteins, has a poor prognosis and establishes a significant positive correlation with MYC and FOXP1 over-expression in this entity.

  15. Mitochondrial DNA mutations in mutator mice confer respiration defects and B-cell lymphoma development.

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    Takayuki Mito

    Full Text Available Mitochondrial DNA (mtDNA mutator mice are proposed to express premature aging phenotypes including kyphosis and hair loss (alopecia due to their carrying a nuclear-encoded mtDNA polymerase with a defective proofreading function, which causes accelerated accumulation of random mutations in mtDNA, resulting in expression of respiration defects. On the contrary, transmitochondrial mito-miceΔ carrying mtDNA with a large-scale deletion mutation (ΔmtDNA also express respiration defects, but not express premature aging phenotypes. Here, we resolved this discrepancy by generating mtDNA mutator mice sharing the same C57BL/6J (B6J nuclear background with that of mito-miceΔ. Expression patterns of premature aging phenotypes are very close, when we compared between homozygous mtDNA mutator mice carrying a B6J nuclear background and selected mito-miceΔ only carrying predominant amounts of ΔmtDNA, in their expression of significant respiration defects, kyphosis, and a short lifespan, but not the alopecia. Therefore, the apparent discrepancy in the presence and absence of premature aging phenotypes in mtDNA mutator mice and mito-miceΔ, respectively, is partly the result of differences in the nuclear background of mtDNA mutator mice and of the broad range of ΔmtDNA proportions of mito-miceΔ used in previous studies. We also provided direct evidence that mtDNA abnormalities in homozygous mtDNA mutator mice are responsible for respiration defects by demonstrating the co-transfer of mtDNA and respiration defects from mtDNA mutator mice into mtDNA-less (ρ(0 mouse cells. Moreover, heterozygous mtDNA mutator mice had a normal lifespan, but frequently developed B-cell lymphoma, suggesting that the mtDNA abnormalities in heterozygous mutator mice are not sufficient to induce a short lifespan and aging phenotypes, but are able to contribute to the B-cell lymphoma development during their prolonged lifespan.

  16. Nanoscale mapping and organization analysis of target proteins on cancer cells from B-cell lymphoma patients

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    Li, Mi [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Xiao, Xiubin [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China); Liu, Lianqing, E-mail: lqliu@sia.cn [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Xi, Ning, E-mail: xin@egr.msu.edu [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong (China); Wang, Yuechao; Dong, Zaili [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Zhang, Weijing, E-mail: zhangwj3072@163.com [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China)

    2013-11-01

    CD20, a membrane protein highly expressed on most B-cell lymphomas, is an effective target demonstrated in clinical practice for treating B-cell non-Hodgkin's lymphoma (NHL). Rituximab is a monoclonal antibody against CD20. In this work, we applied atomic force microscopy (AFM) to map the nanoscale distribution of CD20 molecules on the surface of cancer cells from clinical B-cell NHL patients under the assistance of ROR1 fluorescence recognition (ROR1 is a specific cell surface marker exclusively expressed on cancer cells). First, the ROR1 fluorescence labeling experiments showed that ROR1 was expressed on cancer cells from B-cell lymphoma patients, but not on normal cells from healthy volunteers. Next, under the guidance of ROR1 fluorescence, the rituximab-conjugated AFM tips were moved to cancer cells to image the cellular morphologies and detect the CD20-rituximab interactions on the cell surfaces. The distribution maps of CD20 on cancer cells were constructed by obtaining arrays of (16×16) force curves in local areas (500×500 nm{sup 2}) on the cell surfaces. The experimental results provide a new approach to directly investigate the nanoscale distribution of target protein on single clinical cancer cells. - Highlights: • Cancer cells were recognized from healthy cells by ROR1 fluorescence labeling. • The nanoscale distribution of CD20 on cancer cells was characterized. • The distribution of CD20 was non-uniform on the surface of cancer cells.

  17. Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin's Lymphoma Risk and Survival.

    Directory of Open Access Journals (Sweden)

    Kaspar René Nielsen

    Full Text Available Malignant B-cell clones are affected by both acquired genetic alterations and by inherited genetic variations changing the inflammatory tumour microenvironment.We investigated 50 inflammatory response gene polymorphisms in 355 B-cell non-Hodgkin's lymphoma (B-NHL samples encompassing 216 diffuse large B cell lymphoma (DLBCL and 139 follicular lymphoma (FL and 307 controls. The effect of single genes and haplotypes were investigated and gene-expression analysis was applied for selected genes. Since interaction between risk genes can have a large impact on phenotype, two-way gene-gene interaction analysis was included.We found inherited SNPs in genes critical for inflammatory pathways; TLR9, IL4, TAP2, IL2RA, FCGR2A, TNFA, IL10RB, GALNT12, IL12A and IL1B were significantly associated with disease risk and SELE, IL1RN, TNFA, TAP2, MBL2, IL5, CX3CR1, CHI3L1 and IL12A were, associated with overall survival (OS in specific diagnostic entities of B-NHL. We discovered noteworthy interactions between DLBCL risk alleles on IL10 and IL4RA and FL risk alleles on IL4RA and IL4. In relation to OS, a highly significant interaction was observed in DLBCL for IL4RA (rs1805010 * IL10 (rs1800890 (HR = 0.11 (0.02-0.50. Finally, we explored the expression of risk genes from the gene-gene interaction analysis in normal B-cell subtypes showing a different expression of IL4RA, IL10, IL10RB genes supporting a pathogenetic effect of these interactions in the germinal center.The present findings support the importance of inflammatory genes in B-cell lymphomas. We found association between polymorphic sites in inflammatory response genes and risk as well as outcome in B-NHL and suggest an effect of gene-gene interactions during the stepwise oncogenesis.

  18. PI3Kδ inhibition augments the efficacy of rapamycin in suppressing proliferation of Epstein-Barr virus (EBV)+ B cell lymphomas.

    Science.gov (United States)

    Furukawa, S; Wei, L; Krams, S M; Esquivel, C O; Martinez, O M

    2013-08-01

    Posttransplant lymphoproliferative disorder (PTLD) continues to be a devastating and potentially life-threatening complication in organ transplant recipients. PTLD is associated with EBV infection and can result in malignant B cell lymphomas. Here we demonstrate that the PI3K/Akt/mTOR pathway is highly activated in EBV+ B cell lymphoma lines derived from patients with PTLD. Treatment with the mTORC1 inhibitor Rapamycin (RAPA) partially inhibited the proliferation of EBV+ B cell lines. Resistance to RAPA treatment correlated with high levels of Akt phosphorylation. An mTORC1/2 inhibitor and a PI3K/mTOR dual inhibitor suppressed Akt phosphorylation and showed a greater anti-proliferative effect on EBV+ B lymphoma lines compared to RAPA. EBV+ B cell lymphoma lines expressed high levels of PI3Kδ. We demonstrate that PI3Kδ is responsible for Akt activation in EBV+ B cell lymphomas, and that selective inhibition of PI3Kδ by either siRNA, or a small molecule inhibitor, augmented the anti-proliferative effect of RAPA on EBV+ B cell lymphomas. These results suggest that PI3Kδ is a novel, potential therapeutic target for the treatment of EBV-associated PTLD and that combined blockade of PI3Kδ and mTOR provides increased efficacy in inhibiting proliferation of EBV+ B cell lymphomas.

  19. Rituximab maintenance therapy for patients with diffuse large B-cell lymphoma: A meta-analysis

    Science.gov (United States)

    Li, Juan

    2017-01-01

    Purpose The addition of rituximab to standard chemotherapy has significantly improved survival in patients with lymphoma. Recently, maintenance therapy with rituximab has been shown to prevent relapse and provide survival benefits for patients with follicular or mantle cell lymphoma. However, the effects of rituximab in patients with diffuse large B-cell lymphoma (DLBCL) remain unclear. Two new studies involving rituximab in the treatment of DLBCL were performed this past year. We performed a meta analysis to evaluate the effects of rituximab maintenance treatment of patients with DLBCL. Methods Several databases (PubMed, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials) databases were reviewed for relevant randomized controlled trials published prior to May, 2016. Two reviewers assessed the quality of the included studies and extracted data independently. The hazard ratios (HRs) for time-to-event data and relative risks (RRs) for the other data were pooled and estimated. Results Totally 5 studies including 1740 patients were eligible for the meta-analysis. Compared to the observation group, patients who received rituximab maintenance therapy had significantly improved event-free survival (EFS) (HR = 0.80, 95% CI: 0.65–0.98) and progression-free survival (PFS) (HR = 0.72, 95% CI: 0.54–0.94). However, there was no statistically significant difference in overall survival (OS) (HR = 0.66, 95% CI: 0.27–1.29). A subgroup analysis suggested that male patients may benefit from rituximab maintenance therapy with a better EFS (HR = 0.53, 95% CI: 0.34–0.82-), while this advantage was not observed in female patients (HR = 0.99, 95% CI: 0.64–1.52). Conclusions Rituximab maintenance may provide survival benefits beyond that afforded by first- and second-line chemotherapy alone, especially in male patients. However, maintenance rituximab treatment may cause more adverse events. It is recommended that both survival benefits and adverse events should

  20. Epstein-Barr virus positive B-cell lymphoproliferative disorder/polymorphous B-cell lymphoma of the urinary bladder: A case report with review of literature

    Directory of Open Access Journals (Sweden)

    Sandhya Sundaram

    2009-01-01

    Full Text Available We report an unusual case of a localized Epstein-Barr virus (EBV-positive B cell lymphoproliferative disorder (LPD/polymorphous B cell lymphoma of the urinary bladder in a 67 years old female patient. She had no known predisposing immunodeficiencies and presented with recent onset of hematuria. The CT and cystoscopic examination revealed a localized 2.5 cm polypoid or plaque-like mucosal mass on the right posterior and lateral wall of the bladder. The biopsy sample showed a diffuse and densely polymorphous atypical lymphoid infiltrate admixed with numerous small lymphocytes, histiocytes and occasional plasma cells and neutrophils. The large atypical cells were CD20+, CD79a+, CD30+, CD43+ and they were strongly positive for EBV by in situ hybridization using anti-EBER-1 probe. Polymerase chain reaction (PCR for immunoglobulin heavy chain gene rearrangement study showed a clonal gene rearrangement. The findings indicated EBV+LPD of the bladder. Primary lymphoma of bladder is rare and primary EBV+LPD of the bladder has not been previously described. Potential misdiagnosis of poorly differentiated urothelial carcinoma can occur and accurate diagnosis depends on comprehensive immunohistochemical and molecular workups.

  1. Cyclophosphamide pharmacokinetics and pharmacogenetics in children with B-cell non-Hodgkin's lymphoma

    Science.gov (United States)

    Veal, Gareth J.; Cole, Michael; Chinnaswamy, Girish; Sludden, Julieann; Jamieson, David; Errington, Julie; Malik, Ghada; Hill, Christopher R.; Chamberlain, Thomas; Boddy, Alan V.

    2016-01-01

    Introduction Variation in cyclophosphamide pharmacokinetics and metabolism has been highlighted as a factor that may impact on clinical outcome in various tumour types. The current study in children with B-cell non-Hodgkin's lymphoma (NHL) was designed to corroborate previous findings in a large prospective study incorporating genotype for common polymorphisms known to influence cyclophosphamide pharmacology. Methods A total of 644 plasma samples collected over a 5 year period, from 49 B-cell NHL patients ≤18 years receiving cyclophosphamide (250 mg/m2), were used to characterise a population pharmacokinetic model. Polymorphisms in genes including CYP2B6 and CYP2C19 were analysed. Results A two-compartment model provided the best fit of the population analysis. The mean cyclophosphamide clearance value following dose 1 was significantly lower than following dose 5 (1.83 ± 1.07 versus 3.68 ± 1.43 L/h/m2, respectively; mean ± standard deviation from empirical Bayes estimates; P < 0.001). The presence of at least one CYP2B6*6 variant allele was associated with a lower cyclophosphamide clearance following both dose 1 (1.54 ± 0.11 L/h/m2 versus 2.20 ± 0.31 L/h/m2, P = 0.033) and dose 5 (3.12 ± 0.17 L/h/m2 versus 4.35 ± 0.37 L/h/m2, P = 0.0028), as compared to homozygous wild-type patients. No pharmacokinetic parameters investigated were shown to have a significant influence on progression free survival. Conclusion The results do not support previous findings of a link between cyclophosphamide pharmacokinetics or metabolism and disease recurrence in childhood B-cell NHL. While CYP2B6 genotype was shown to influence pharmacokinetics, there was no clear impact on clinical outcome. PMID:26773420

  2. The anti-lymphoma activity of antiviral therapy in HCV-associated B-cell non-Hodgkin lymphomas: a meta-analysis.

    Science.gov (United States)

    Peveling-Oberhag, J; Arcaini, L; Bankov, K; Zeuzem, S; Herrmann, E

    2016-07-01

    Many epidemiological studies provide solid evidence for an association of chronic hepatitis C virus (HCV) infection with B-cell non-Hodgkin's lymphoma (B-NHL). However, the most convincing evidence for a causal relationship between HCV infection and lymphoma development is the observation of B-NHL regression after HCV eradication by antiviral therapy (AVT). We conducted a literature search to identify studies that included patients with HCV-associated B-NHL (HCV-NHL) who received AVT, with the intention to treat lymphoma and viral disease at the same time. The primary end point was the correlation of sustained virological response (SVR) under AVT with lymphoma response. Secondary end points were overall lymphoma response rates and HCV-NHL response in correlation with lymphoma subtypes. We included 20 studies that evaluated the efficacy of AVT in HCV-NHL (n = 254 patients). Overall lymphoma response rate through AVT was 73% [95%>confidence interval, (CI) 67-78%]. Throughout studies there was a strong association between SVR and lymphoma response (83% response rate, 95%>CI, 76-88%) compared to a failure in achieving SVR (53% response rate, 95%>CI, 39-67%, P = 0.0002). There was a trend towards favourable response for AVT in HCV-associated marginal zone lymphomas (response rate 81%, 95%>CI, 74-87%) compared to nonmarginal zone origin (response rate 71%, 95%>CI, 61-79%, P = 0.07). In conclusion, in the current meta-analysis, the overall response rate of HCV-NHL under AVT justifies the recommendation for AVT as first-line treatment in patients who do not need immediate conventional treatment. The strong correlation of SVR and lymphoma regression supports the hypothesis of a causal relationship of HCV and lymphomagenesis.

  3. Synchronous, primary, diffuse, large B-cell lymphomas involving the ethmoid sinus and epiglottis: a rare clinical entity.

    Science.gov (United States)

    Yoon, Young-Ho; Park, Won-Young; Choi, Young-Jin; Cho, Kyu-Sup

    2013-03-01

    Non-Hodgkin's lymphoma (NHL) affecting the ethmoid sinus and epiglottis is uncommon. Furthermore, synchronous NHLs involving the ethmoid sinus and epiglottis are extremely rare and have not been reported previously. This article reports synchronous, primary, diffuse, large B-cell lymphoma (DLBCL) arising in the ethmoid sinus and epiglottis, which was successfully treated by immunochemotherapy. A careful examination of the head and neck is necessary to determine the existence of multiple synchronous primary tumors, because primary synchronous occurrence of DLBCL in the head and neck is unusual and can impact the prognosis adversely.

  4. Primary Diffuse Large B-Cell Lymphoma Localized to the Lacrimal Sac: A Case Presentation and Review of the Literature

    OpenAIRE

    Kevin Zarrabi; Ved Desai; Brandom Yim; Gabig, Theodore G.

    2016-01-01

    We report a rare case of diffuse large B-cell lymphoma (DLBCL) of the lacrimal sac in a 50-year-old male. The incidence of primary ocular lymphoma is low and it is considered a rare disease. Moreover, reports of ocular DLBCL are uncommon and the disease remains poorly characterized. Our patient presented for management of osteomyelitis and was incidentally found to have a painless swelling and cyst around his right eye. A PET/CT scan revealed hypermetabolic activity within the lacrimal sac an...

  5. Myelodysplastic Syndrome with Myelofibrosis Transformed to a Precursor B-Cell Acute Lymphoblastic Leukemia: A Case Report with Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ayed A. Algarni

    2012-01-01

    Full Text Available Myelodysplastic syndromes (MDS comprise a group of heterogeneous clonal hematopoietic cell disorders characterized by cytopenias, bone marrow hypercellularity, and increased risk of transformation to acute leukemias. MDS usually transformed to acute myeloid leukemia, and transformation to acute lymphoblastic leukemia (ALL is rare. Herein, we report a unique patient who presented with MDS with myelofibrosis. Two months after the initial diagnosis, she progressed to a precursor B-cell acute lymphoblastic leukemia. She was treated with induction therapy followed by allogenic stem cell transplantation. She was alive and doing well upon last followup. We have also reviewed the literature and discussed the clinicopathologic features of 36 MDS patients who progressed to ALL reported in the literature.

  6. Guidelines for diagnosis, prevention and management of central nervous system involvement in diffuse large B-cell lymphoma patients by the Spanish Lymphoma Group (GELTAMO)

    Science.gov (United States)

    Peñalver, Francisco-Javier; Sancho, Juan-Manuel; de la Fuente, Adolfo; Olave, María-Teresa; Martín, Alejandro; Panizo, Carlos; Pérez, Elena; Salar, Antonio; Orfao, Alberto

    2017-01-01

    Diffuse large B-cell lymphoma patients have a 5% overall risk of central nervous system events (relapse or progression), which account for high morbidity and frequently fatal outcomes,1 and shortened overall survival of <6 months.2 Early diagnosis of central nervous system events is critical for successful treatment and improved prognosis. Identification of patients at risk of central nervous system disease is critical to accurately identify candidates for central nervous system prophylaxis vs. therapy.3–5 This report by the Spanish Lymphoma Group (GELTAMO) aims to provide useful guidelines and recommendations for the prevention, diagnosis, and treatment of central nervous system diffuse large B-cell lymphoma patients with, or at risk of, leptomeningeal and/or brain parenchyma lymphoma relapse. A panel of lymphoma experts working on behalf of GELTAMO reviewed all data published on these topics available in PubMed up to May 2016. Recommendations were classified according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach.6 A practical algorithm based on the proposed recommendations was then developed (Figure 1). Initial discussions among experts were held in May 2014, and final consensus was reached in June 2016. The final manuscript was reviewed by all authors and the Scientific Committee of GELTAMO. PMID:27846613

  7. Primary non-Hodgkin′s lymphoma of the salivary gland: A spectrum of lymphoepithelial sialadenitis, low-grade B-cell lymphoma of mucosa-associated lymphoid tissue with transformation to high-grade lymphoma

    Directory of Open Access Journals (Sweden)

    Agale Shubhangi

    2010-04-01

    Full Text Available Lymphoid infiltrates of the salivary gland can be either reactive or neoplastic. The reactive lesion, lymphoepithelial sialadenitis (LESA may be associated with Sjogren′s syndrome (SS or may occur as an isolated salivary gland enlargement. Patients with LESA/SS have a particularly high risk of subsequently developing lymphoma, which is a low-grade mucosa-associated lymphoid tissue (MALT type lymphoma of the salivary gland. We document a rare case of primary non-Hodgkin′s lymphoma of the parotid gland arising in the background of LESA and with a rare example of transformation from low grade to high-grade B cell lymphoma of MALT type.

  8. Biomarkers of diffuse large B-cell lymphoma: impact on diagnosis, treatment, and prognosis

    Directory of Open Access Journals (Sweden)

    Coutinho R

    2013-02-01

    Full Text Available Rita Coutinho, John GribbenCentre for Haemato-Onocology, Barts Cancer Institute, Queen Mary, University of London, London, United KingdomAbstract: Introduction of immunochemotherapy as frontline treatment for diffuse large B-cell lymphoma (DLBCL has significantly increased survival. However, patients refractory to rituximab-containing regimens have a very poor survival. These differences in clinical behavior might lie behind the biological heterogeneity well recognized in this disease. Advanced molecular research has helped us to define DLBCL subgroups which harbor distinct oncogenic events and response to immunochemotherapy. The field of biomarker discovery in DLBCL has become more complex over the last decade and a broad up-to-date review on this topic is lacking. The aim for this review was to offer the hematology community a comprehensive overview of clinical and biological markers which have a diagnostic and prognostic potential and that might be amenable to therapeutic targeting. Some well known markers are reassessed in light of recent findings.Keywords: DLBCL, immunochemotherapy, rituximab, biomarkers

  9. Antitumor activity of fucoidan against diffuse large B cell lymphoma in vitro and in vivo.

    Science.gov (United States)

    Yang, Guang; Zhang, Qianqiao; Kong, Yuanyuan; Xie, Bingqian; Gao, Minjie; Tao, Yi; Xu, Hongwei; Zhan, Fenghuang; Dai, Bojie; Shi, Jumei; Wu, Xiaosong

    2015-11-01

    Fucoidan is one of the major sulfated polysaccharides isolated from brown seaweeds. In this study, we determined the anti-cancer activity of fucoidan on diffuse large B cell lymphoma (DLBCL) cells both in vitro and in vivo. Fucoidan inhibited the growth of DLBCL cells in a dose- and time-dependent manner, and fucoidan treatment provoked G0/G1 cell cycle arrest, which was accompanied by p21 up-regulation and cyclin D1, Cdk4, and Cdk6 down-regulation. Fucoidan also induced caspase-dependent cell apoptosis in DLBCL cell lines and primary DLBCL cell. In addition, fucoidan treatment caused the loss of mitochondrial membrane potential and the release of cytochrome c and apoptosis-inducing factor from the mitochondria into the cytosol. Fucoidan also potentiated the activities of carfilzomib in killing DLBCL cells. Oral administration of fucoidan effectively inhibited tumor growth in xenograft mouse models. Our findings reveal the novel function of fucoidan as an anti-DLBCL agent, which can be used in the clinical treatment of DLBCL.

  10. Low T3 syndrome is a strong prognostic predictor in diffuse large B cell lymphoma.

    Science.gov (United States)

    Gao, Rui; Liang, Jin-Hua; Wang, Li; Zhu, Hua-Yuan; Wu, Wei; Wu, Jia-Zhu; Xia, Yi; Cao, Lei; Fan, Lei; Yang, Tao; Li, Jian-Yong; Xu, Wei

    2017-02-01

    The aim of this study was to evaluate the prognostic effect of low triiodothyronine (T3) syndrome on patients with diffuse large B cell lymphoma (DLBCL). A hundred and eighty-eight patients with detailed thyroid hormone levels at diagnosis of DLBCL were enrolled. Low T3 syndrome was defined as a low serum free T3 (FT3) level with low or normal serum free tetraiodothyronine (FT4) and thyroid stimulating hormone levels. Multivariate Cox regression analysis was used to screen prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver-operator characteristic curves and the corresponding areas under the curve were calculated to assess the predictive accuracy of International Prognostic Index (IPI) and low T3 syndrome. Twenty-four patients were diagnosed with low T3 syndrome, which was associated with worse PFS and OS in the rituximab era. It was an independent prognostic factor for PFS and OS, especially for those with IPI 0-2, extranodal sites ≤1 and stage III-IV. Synchronously low FT3 and FT4 had poorer survival outcome compared to only low FT3 and adding criterion of low T3 syndrome improved the prognostic capacity of IPI for predicting PFS and OS in DLBCL. Low T3 syndrome was found to be a strong prognostic predictor in DLBCL.

  11. A case of cutaneous large B-cell lymphoma of the legs appearing as chronic venous ulceration

    Directory of Open Access Journals (Sweden)

    Alfredo Rossi

    2012-05-01

    Full Text Available We report here a case of a woman with a cutaneous large B-cell lymphoma of the legs. She had a plaque lesion, superficially ulcerated and necrotized with tumorous borders situated on the posterior side of the right leg and two red or bluish-red nodular lesions. A skin biopsy from both nodular and plaque lesion showed a diffuse infiltrate of atypical large B cells CD20+ and CD79a+, spanning epidermis, dermis and subcutaneous tissue. A therapeutic approach containing anti-CD20 monoclonal antibody (rituximab was suggested.

  12. ‘Les liaisons dangereuses’: Hepatitis C, Rituximab and B-cell non-Hodgkin’s lymphomas

    Institute of Scientific and Technical Information of China (English)

    Massimo; Marignani; Michela; di; Fonzo; Paola; Begini; Elia; Gigante; Ilaria; Deli; Adriano; M; Pellicelli; Sara; Gallina; Emanuela; de; Santis; Gianfranco; Delle; Fave; M; Christina; Cox

    2012-01-01

    Rituximab has provided a revolutionary contribution to the treatment of B-cell non-Hodgkin’s lymphomas (NHL). A high prevalence of hepatitis C virus (HCV) infection has been described in B-cell NHL patients. Cases of liver dysfunction in HCV-positive patients have been reported with Rituximab-containing regimens. In this paper we review the recent data regarding the effects of Rituximab in NHL patients with HCV infection. We also added a section devoted to improving communication between oncohaematologists and hepatologists. Furthermore, we propose a common methodological ground to study hepatic toxicity emerging during chemotherapy.

  13. Protein kinase CK2 is widely expressed in follicular, Burkitt and diffuse large B-cell lymphomas and propels malignant B-cell growth.

    Science.gov (United States)

    Pizzi, Marco; Piazza, Francesco; Agostinelli, Claudio; Fuligni, Fabio; Benvenuti, Pietro; Mandato, Elisa; Casellato, Alessandro; Rugge, Massimo; Semenzato, Gianpietro; Pileri, Stefano A

    2015-03-30

    Serine-threonine kinase CK2 is highly expressed and pivotal for survival and proliferation in multiple myeloma, chronic lymphocytic leukemia and mantle cell lymphoma. Here, we investigated the expression of α catalytic and β regulatory CK2 subunits by immunohistochemistry in 57 follicular (FL), 18 Burkitt (BL), 52 diffuse large B-cell (DLBCL) non-Hodgkin lymphomas (NHL) and in normal reactive follicles. In silico evaluation of available Gene Expression Profile (GEP) data sets from patients and Western blot (WB) analysis in NHL cell-lines were also performed. Moreover, the novel, clinical-grade, ATP-competitive CK2-inhibitor CX-4945 (Silmitasertib) was assayed on lymphoma cells. CK2 was detected in 98.4% of cases with a trend towards a stronger CK2α immunostain in BL compared to FL and DLBCL. No significant differences were observed between Germinal Center B (GCB) and non-GCB DLBCL types. GEP data and WB confirmed elevated CK2 mRNA and protein levels as well as active phosphorylation of specific targets in NHL cells. CX-4945 caused a dose-dependent growth-arresting effect on GCB, non-GCB DLBCL and BL cell-lines and it efficiently shut off phosphorylation of NF-κB RelA and CDC37 on CK2 target sites. Thus, CK2 is highly expressed and could represent a suitable therapeutic target in BL, FL and DLBCL NHL.

  14. Fluorine-18-fluorodeoxyglucose positron emission tomography for interim response assessment of advanced-stage Hodgkin's lymphoma and diffuse large B-cell lymphoma: a systematic review

    DEFF Research Database (Denmark)

    Terasawa, T.; Lau, J.; Bardet, S.

    2009-01-01

    PURPOSE: To systematically review the prognostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) for interim response assessment of patients with untreated advanced-stage Hodgkin's lymphoma (HL) or diffuse large B-cell lymphoma (DLBCL). METHODS: MEDLINE, EMBASE......-stage HL, FDG-PET performed after a few cycles of standard chemotherapy seems to be a reliable prognostic test to identify poor responders, warranting prospective studies to assess PET-based treatment strategies. For DLBCL, no reliable conclusions can be drawn due to heterogeneity. Interim PET remains...

  15. A reliable Raman-spectroscopy-based approach for diagnosis, classification and follow-up of B-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Managò, Stefano; Valente, Carmen; Mirabelli, Peppino; Circolo, Diego; Basile, Filomena; Corda, Daniela; de Luca, Anna Chiara

    2016-04-01

    Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder that shows high mortality rates due to immature lymphocyte B-cell proliferation. B-ALL diagnosis requires identification and classification of the leukemia cells. Here, we demonstrate the use of Raman spectroscopy to discriminate normal lymphocytic B-cells from three different B-leukemia transformed cell lines (i.e., RS4;11, REH, MN60 cells) based on their biochemical features. In combination with immunofluorescence and Western blotting, we show that these Raman markers reflect the relative changes in the potential biological markers from cell surface antigens, cytoplasmic proteins, and DNA content and correlate with the lymphoblastic B-cell maturation/differentiation stages. Our study demonstrates the potential of this technique for classification of B-leukemia cells into the different differentiation/maturation stages, as well as for the identification of key biochemical changes under chemotherapeutic treatments. Finally, preliminary results from clinical samples indicate high consistency of, and potential applications for, this Raman spectroscopy approach.

  16. Portraying the Expression Landscapes of B-CellLymphoma-Intuitive Detection of Outlier Samples and of Molecular Subtypes

    Directory of Open Access Journals (Sweden)

    Lydia Hopp

    2013-12-01

    Full Text Available We present an analytic framework based on Self-Organizing Map (SOM machine learning to study large scale patient data sets. The potency of the approach is demonstrated in a case study using gene expression data of more than 200 mature aggressive B-cell lymphoma patients. The method portrays each sample with individual resolution, characterizes the subtypes, disentangles the expression patterns into distinct modules, extracts their functional context using enrichment techniques and enables investigation of the similarity relations between the samples. The method also allows to detect and to correct outliers caused by contaminations. Based on our analysis, we propose a refined classification of B-cell Lymphoma into four molecular subtypes which are characterized by differential functional and clinical characteristics.

  17. ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype

    Science.gov (United States)

    Hirabayashi, Shinsuke; Ohki, Kentaro; Nakabayashi, Kazuhiko; Ichikawa, Hitoshi; Momozawa, Yukihide; Okamura, Kohji; Yaguchi, Akinori; Terada, Kazuki; Saito, Yuya; Yoshimi, Ai; Ogata-Kawata, Hiroko; Sakamoto, Hiromi; Kato, Motohiro; Fujimura, Junya; Hino, Moeko; Kinoshita, Akitoshi; Kakuda, Harumi; Kurosawa, Hidemitsu; Kato, Keisuke; Kajiwara, Ryosuke; Moriwaki, Koichi; Morimoto, Tsuyoshi; Nakamura, Kozue; Noguchi, Yasushi; Osumi, Tomoo; Sakashita, Kazuo; Takita, Junko; Yuza, Yuki; Matsuda, Koich; Yoshida, Teruhiko; Matsumoto, Kenji; Hata, Kenichiro; Kubo, Michiaki; Matsubara, Yoichi; Fukushima, Takashi; Koh, Katsuyoshi; Manabe, Atsushi; Ohara, Akira; Kiyokawa, Nobutaka

    2017-01-01

    Fusion genes involving ZNF384 have recently been identified in B-cell precursor acute lymphoblastic leukemia, and 7 fusion partners have been reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or polymerase chain reaction. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384. Including the EP300-ZNF384 that we reported recently, the total frequency of ZNF384-related fusion genes was 4.1% in 291 B-cell precursor acute lymphoblastic leukemia patients enrolled in a single clinical trial, and TCF3-ZNF384 was the most recurrent, with a frequency of 2.4%. The characteristic immunophenotype of weak CD10 and aberrant CD13 and/or CD33 expression was revealed to be a common feature of the leukemic cells harboring ZNF384-related fusion genes. The signature gene expression profile in TCF3-ZNF384-positive patients was enriched in hematopoietic stem cell features and related to that of EP300-ZNF384-positive patients, but was significantly distinct from that of TCF3-PBX1-positive and ZNF384-fusion-negative patients. However, clinical features of TCF3-ZNF384-positive patients are markedly different from those of EP300-ZNF384-positive patients, exhibiting higher cell counts and a younger age at presentation. TCF3-ZNF384-positive patients revealed a significantly poorer steroid response and a higher frequency of relapse, and the additional activating mutations in RAS signaling pathway genes were detected by whole exome analysis in some of the cases. Our observations indicate that ZNF384-related fusion genes consist of a distinct subgroup of B-cell precursor acute lymphoblastic leukemia with a characteristic immunophenotype, while the clinical features depend on the functional properties of individual fusion partners. PMID:27634205

  18. Molecular cloning and nucleotide sequence of a transforming gene detected by transfection of chicken B-cell lymphoma DNA

    Science.gov (United States)

    Goubin, Gerard; Goldman, Debra S.; Luce, Judith; Neiman, Paul E.; Cooper, Geoffrey M.

    1983-03-01

    A transforming gene detected by transfection of chicken B-cell lymphoma DNA has been isolated by molecular cloning. It is homologous to a conserved family of sequences present in normal chicken and human DNAs but is not related to transforming genes of acutely transforming retroviruses. The nucleotide sequence of the cloned transforming gene suggests that it encodes a protein that is partially homologous to the amino terminus of transferrin and related proteins although only about one tenth the size of transferrin.

  19. CGCI Investigators Reveal Comprehensive Landscape of Diffuse Large B-Cell Lymphoma (DLBCL) Genomes | Office of Cancer Genomics

    Science.gov (United States)

    Researchers from British Columbia Cancer Agency used whole genome sequencing to analyze 40 DLBCL cases and 13 cell lines in order to fill in the gaps of the complex landscape of DLBCL genomes. Their analysis, “Mutational and structural analysis of diffuse large B-cell lymphoma using whole genome sequencing,” was published online in Blood on May 22. The authors are Ryan Morin, Marco Marra, and colleagues.  

  20. Prognostic significance of Epstein-Barr virus DNA detection in pretreatment serum in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Okamoto, Akinao; Yanada, Masamitsu; Miura, Hiroki; Inaguma, Yoko; Tokuda, Masutaka; Morishima, Satoko; Kanie, Tadaharu; Yamamoto, Yukiya; Mizuta, Shuichi; Akatsuka, Yoshiki; Yoshikawa, Tetsushi; Mizoguchi, Yoshikazu; Nakamura, Shigeo; Okamoto, Masataka; Emi, Nobuhiko

    2015-11-01

    It is still a matter of debate whether detection of Epstein-Barr virus (EBV) DNA in pretreatment serum has clinical implications for diffuse large B-cell lymphoma. For this study, we measured EBV DNA load in pretreatment serum from 127 diffuse large B-cell lymphoma patients without any underlying immunodeficiency to evaluate its effects on clinical manifestations and prognosis. Anthracycline-based chemotherapy in combination with rituximab was given as initial therapy for 119 patients (94%). Epstein-Barr virus DNA was detected in 15 patients (12%), who were older (P = 0.005) and tended to be at a more advanced disease stage (P = 0.053). They showed significantly worse progression-free survival (PFS) and overall survival (OS) than other patients (P EBV-encoded small RNA in situ hybridization was known for 123 patients; 6 of 8 positive patients (75%) and 9 of 115 negative patients (8%) had detectable EBV DNA in pretreatment serum. While patients positive for EBV-encoded small RNA had significantly worse PFS and OS than negative patients (P = 0.001 and P = 0.029, respectively), EBV DNA detection in pretreatment serum was associated with poorer PFS and OS even for the 115 patients negative for EBV-encoded small RNA (P EBV DNA detection in pretreatment serum may have an adverse prognostic impact for patients with diffuse large B-cell lymphoma.

  1. Multifocal Gastric Ulcers Caused by Diffuse Large B Cell Lymphoma in a Patient With Significant Weight Loss

    Directory of Open Access Journals (Sweden)

    Mark A. Gromski MD

    2016-12-01

    Full Text Available Primary gastrointestinal (GI lymphoma is a heterogeneous disease with varied clinical presentations. The stomach is the most common GI site and accounts for 70% to 75% of GI lymphomas. We present a patient with gastric diffuse large B cell lymphoma (DLBCL who presented with significant weight loss, early satiety, and multifocal ulcerated gastric lesions. Esophagoduodenoscopy should be performed in patients presenting with warning symptoms as in our case. Diagnosis is usually made by endoscopic biopsies. Multiple treatment modalities including surgery, radiotherapy, and chemotherapy have been used. Advancements in endoscopic and pathologic technology decrease turnaround time for diagnosis and treatment initiation, thus reducing the need for surgery. Health care providers should maintain a high level of suspicion and consider gastric DLBCL as part of the differential diagnosis, especially in those with warning symptoms such as weight loss and early satiety with abnormal endoscopic findings.

  2. [Parapsoriasis en plaque suspected of progression to mycosis fungoides associated with extranodal malignant B cell lymphoma of the cheek].

    Science.gov (United States)

    Onizuka, T; Satou, S; Koike, M; Ishiyama, T; Tomoyasu, S; Tsuruoka, N; Ohta, H; Fujisawa, R; Yamaguchi, A; Tashiro, T

    1993-06-01

    A 59-year-old female, clinically diagnosed as having parapsoriasis en plaque for ten years, was referred on June 1991 to the Department of Oral Surgery in the Dental School of showa University with a complaint of painless swelling of the left malar area. The swelling was found to have been caused by a tumor. Since the excised tumor was suspected to be a malignant lymphoma, she was admitted to our hospital. The specimen was subsequently confirmed to be a malignant lymphoma of the diffuse large cell type according to the LSG classification, and was immunologically confirmed to be a B cell lymphoma. In addition, the excised skin was suspected of incipient mycosis fungoides. She was classified as having stage IE disease according to her bone marrow biopsy and other examinations. she was treated with combination of chemotherapy (CHOP) and radiation therapy. This subject was interesting because her tumor probably resulted from a parapsoriasis en plaque skin lesion.

  3. Primary Diffuse Large B-Cell Lymphoma Localized to the Lacrimal Sac: A Case Presentation and Review of the Literature.

    Science.gov (United States)

    Zarrabi, Kevin; Desai, Ved; Yim, Brandom; Gabig, Theodore G

    2016-01-01

    We report a rare case of diffuse large B-cell lymphoma (DLBCL) of the lacrimal sac in a 50-year-old male. The incidence of primary ocular lymphoma is low and it is considered a rare disease. Moreover, reports of ocular DLBCL are uncommon and the disease remains poorly characterized. Our patient presented for management of osteomyelitis and was incidentally found to have a painless swelling and cyst around his right eye. A PET/CT scan revealed hypermetabolic activity within the lacrimal sac and a subsequent excisional biopsy of the mass yielded histopathology consistent with DLBCL. Consequently, the patient underwent treatment with R-CHOP therapy. The patient responded well to chemotherapy with a substantial shrinkage in tumor burden and the disease remained localized. Herein, we present a rare case of primary ocular lymphoma, highlight the importance of early diagnosis, and review current treatment modalities.

  4. Primary Diffuse Large B-Cell Lymphoma Localized to the Lacrimal Sac: A Case Presentation and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Kevin Zarrabi

    2016-01-01

    Full Text Available We report a rare case of diffuse large B-cell lymphoma (DLBCL of the lacrimal sac in a 50-year-old male. The incidence of primary ocular lymphoma is low and it is considered a rare disease. Moreover, reports of ocular DLBCL are uncommon and the disease remains poorly characterized. Our patient presented for management of osteomyelitis and was incidentally found to have a painless swelling and cyst around his right eye. A PET/CT scan revealed hypermetabolic activity within the lacrimal sac and a subsequent excisional biopsy of the mass yielded histopathology consistent with DLBCL. Consequently, the patient underwent treatment with R-CHOP therapy. The patient responded well to chemotherapy with a substantial shrinkage in tumor burden and the disease remained localized. Herein, we present a rare case of primary ocular lymphoma, highlight the importance of early diagnosis, and review current treatment modalities.

  5. Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Randa; Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez, Alma [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shihadeh, Ferial; Pinnix, Chelsea C.; Arzu, Isadora; Reed, Valerie K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Oki, Yasuhiro; Westin, Jason R.; Fayad, Luis E.; Medeiros, L. Jeffrey [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dabaja, Bouthaina, E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-05-01

    Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS.

  6. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Wu, Lin; Visco, Carlo;

    2012-01-01

    TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. ...

  7. The contribution of HGAL/GCET2 in immunohistological algorithms: a comparative study in 424 cases of nodal diffuse large B-cell lymphoma.

    Science.gov (United States)

    Gualco, Gabriela; Bacchi, Lívia M; Domeny-Duarte, Pollyanna; Natkunam, Yasodha; Bacchi, Carlos E

    2012-11-01

    Diffuse large B-cell lymphoma can be subclassified into at least two molecular subgroups by gene expression profiling: germinal center B-cell like and activated B-cell like diffuse large B-cell lymphoma. Several immunohistological algorithms have been proposed as surrogates to gene expression profiling at the level of protein expression, but their reliability has been an issue of controversy. Furthermore, the proportion of misclassified cases of germinal center B-cell subgroup by immunohistochemistry, in all reported algorithms, is higher compared with germinal center B-cell cases defined by gene expression profiling. We analyzed 424 cases of nodal diffuse large B-cell lymphoma with the panel of markers included in the three previously described algorithms: Hans, Choi, and Tally. To test whether the sensitivity of detecting germinal center B-cell cases could be improved, the germinal center B-cell marker HGAL/GCET2 was also added to all three algorithms. Our results show that the inclusion of HGAL/GCET2 significantly increased the detection of germinal center B-cell cases in all three algorithms (P<0.001). The proportions of germinal center B-cell cases in the original algorithms were 27%, 34%, and 19% for Hans, Choi, and Tally, respectively. In the modified algorithms, with the inclusion of HGAL/GCET2, the frequencies of germinal center B-cell cases were increased to 38%, 48%, and 35%, respectively. Therefore, HGAL/GCET2 protein expression may function as a marker for germinal center B-cell type diffuse large B-cell lymphoma. Consideration should be given to the inclusion of HGAL/GCET2 analysis in algorithms to better predict the cell of origin. These findings bear further validation, from comparison to gene expression profiles and from clinical/therapeutic data.

  8. A Unique “Composite” PTLD with Diffuse Large B-Cell and T/Anaplastic Large Cell Lymphoma Components Occurring 17 Years after Transplant

    Directory of Open Access Journals (Sweden)

    Kristin La Fortune

    2013-01-01

    Full Text Available Posttransplant lymphoproliferative disorder (PTLD comprises a spectrum ranging from polyclonal hyperplasia to aggressive monoclonal lymphomas. The majority of PTLDs are of B-cell origin while T-cell PTLDs and Hodgkin lymphoma-like PTLDs are uncommon. Here, we report a unique case of a 56-year-old man in whom a lymphoma with two distinct components developed as a duodenal mass seventeen years following a combined kidney-pancreas transplant. This PTLD, which has features not previously reported in the literature, consisted of one component of CD20 positive and EBV negative monomorphic diffuse large B-cell lymphoma. The other component showed anaplastic morphology, expressed some but not all T-cell markers, failed to express most B-cell markers except for PAX5, and was diffusely EBV positive. Possible etiologies for this peculiar constellation of findings are discussed and the literature reviewed for “composite-like” lymphomas late in the posttransplant setting.

  9. Epitope-driven DNA vaccine design employing immunoinformatics against B-cell lymphoma: a biotech's challenge.

    Science.gov (United States)

    Iurescia, Sandra; Fioretti, Daniela; Fazio, Vito Michele; Rinaldi, Monica

    2012-01-01

    DNA vaccination has been widely explored to develop new, alternative and efficient vaccines for cancer immunotherapy. DNA vaccines offer several benefits such as specific targeting, use of multiple genes to enhance immunity and reduced risk compared to conventional vaccines. Rapid developments in molecular biology and immunoinformatics enable rational design approaches. These technologies allow construction of DNA vaccines encoding selected tumor antigens together with molecules to direct and amplify the desired effector pathways, as well as highly targeted vaccines aimed at specific epitopes. Reliable predictions of immunogenic T cell epitope peptides are crucial for rational vaccine design and represent a key problem in immunoinformatics. Computational approaches have been developed to facilitate the process of epitope detection and show potential applications to the immunotherapeutic treatment of cancer. In this review a number of different epitope prediction methods are briefly illustrated and effective use of these resources to support experimental studies is described. Epitope-driven vaccine design employs these bioinformatics algorithms to identify potential targets of vaccines against cancer. In this paper the selection of T cell epitopes to develop epitope-based vaccines, the need for CD4(+) T cell help for improved vaccines and the assessment of vaccine performance against tumor are reviewed. We focused on two applications, namely prediction of novel T cell epitopes and epitope enhancement by sequence modification, and combined rationale design with bioinformatics for creation of new synthetic mini-genes. This review describes the development of epitope-based DNA vaccines and their antitumor effects in preclinical research against B-cell lymphoma, corroborating the usefulness of this platform as a potential tool for cancer therapy. Achievements in the field of DNA vaccines allow to overcome hurdles to clinical translation. In a scenario where the vaccine

  10. Comparative Study on Rituximab Combined with Chemotherapy and Single Chemotherapy for Diffuse Large B Cell Lymphoma

    Institute of Scientific and Technical Information of China (English)

    FENG Ji-feng

    2015-01-01

    Objective:To explore the clinical efifcacy and safety of rituximab combined with chemotherapy and single chemotherapy for diffuse large B cell lymphoma (DLBCL). Methods:A total of 97 patients with DLBCL were selected. Patients treated by single chemotherapy were designed as control group, while those by rituximab combined with chemotherapy as observational group. All patients were treated for at least 4 cycles. The short-term and long-term efifcacy and related adverse reactions of 2 groups were observed. Results:The rate of complete remission (CR) in observational group was signiifcantly higher than in control group (χ2=4.6589,P=0.0309). However, there was no signiifcant difference in objective remission rate (ORR) between 2 groups (P=0.3651). The rates of 3-year overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were 80.30% (53/66), 69.70% (46/66) and 59.09% (39/66) in observational group, and 61.29% (19/31), 58.06% (18/31) and 58.06% (18/31) in control group, respectively. The OS in observational group was signiifcantly longer than in control group (P=0.035). However, there was no signiifcant difference in PFS, DFS and rate adverse reactions between 2 groups (P=0.089;P=0.438;χ2=0.1562,P=0.6927). Conclusion: Rituximab combined with chemotherapy can improve the efficacy of DLBCL without increasing the adverse reactions, which can be used as the ifrst-line treatment for DLBCL, thus deserving to be widely applied in clinic.

  11. Comparative Study on Rituximab Combined with Chemotherapy and Single Chemotherapy for Diffuse Large B Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Ji-feng FENG

    2015-06-01

    Full Text Available Objective: To explore the clinical efficacy and safety of rituximab combined with chemotherapy and single chemotherapy for diffuse large B cell lymphoma (DLBCL. Methods: A total of 97 patients with DLBCL were selected. Patients treated by single chemotherapy were designed as control group, while those by rituximab combined with chemotherapy as observational group. All patients were treated for at least 4 cycles. The short-term and long-term efficacy and related adverse reactions of 2 groups were observed. Results: The rate of complete remission (CR in observational group was significantly higher than in control group (χ2=4.6589, P=0.0309. However, there was no significant difference in objective remission rate (ORR between 2 groups (P=0.3651. The rates of 3-year overall survival (OS, progression-free survival (PFS and disease-free survival (DFS were 80.30% (53/66, 69.70% (46/66 and 59.09% (39/66 in observational group, and 61.29% (19/31, 58.06% (18/31 and 58.06% (18/31 in control group, respectively. The OS in observational group was significantly longer than in control group (P=0.035. However, there was no significant difference in PFS, DFS and rate adverse reactions between 2 groups (P=0.089; P=0.438; χ2=0.1562, P=0.6927. Conclusion: Rituximab combined with chemotherapy can improve the efficacy of DLBCL without increasing the adverse reactions, which can be used as the first-line treatment for DLBCL, thus deserving to be widely applied in clinic.

  12. Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Hugo J.A., E-mail: h.j.a.adams@gmail.com [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands); Klerk, John M.H. de [Department of Nuclear Medicine, Meander Medical Center, Amersfoort (Netherlands); Fijnheer, Rob [Department of Hematology, Meander Medical Center, Amersfoort (Netherlands); Dubois, Stefan V. [Department of Pathology, Meander Medical Center, Amersfoort (Netherlands); Nievelstein, Rutger A.J.; Kwee, Thomas C. [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands)

    2015-03-15

    Highlights: •CT is compulsory for staging newly diagnosed DLBCL. •Approximately 13.7% of DLBCL patients have tumor necrosis at CT. •Tumor necrosis status at CT is not associated with any NCCN-IPI factor. •Patients with tumor necrosis at CT have a significantly worse outcome. -- Abstract: Objective: To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Materials and methods: This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. Results: There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ = −0.042, P = 0.765), categorized lactate dehydrogenase (LDH) ratio (ρ = 0.201, P = 0.156), extranodal disease in major organs (φ = −0.245, P = 0.083), Ann Arbor stage III/IV disease (φ = −0.208, P = 0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ = 0.015, P = 0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P = 0.003) and overall survival (P = 0.004). Conclusion: The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL.

  13. HLA-G and MHC Class II Protein Expression in Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Jesionek-Kupnicka, Dorota; Bojo, Marcin; Prochorec-Sobieszek, Monika; Szumera-Ciećkiewicz, Anna; Jabłońska, Joanna; Kalinka-Warzocha, Ewa; Kordek, Radzisław; Młynarski, Wojciech; Robak, Tadeusz; Warzocha, Krzysztof; Lech-Maranda, Ewa

    2016-06-01

    The expression of human leukocyte antigen-G (HLA-G) and HLA class II protein was studied by immunohistochemical staining of lymph nodes from 148 patients with diffuse large B-cell lymphoma (DLBCL) and related to the clinical course of the disease. Negative HLA-G expression was associated with a lower probability of achieving a complete remission (p = 0.04). Patients with negative HLA-G expression tended towards a lower 3-year overall survival (OS) rate compared to those with positive expression of HLA-G (p = 0.08). When restricting the analysis to patients receiving chemotherapy with rituximab, the estimated 3-year OS rate of patients with positive HLA-G expression was 73.3 % compared with 47.5 % (p = 0.03) in those with negative expression. Patients with negative HLA class II expression presented a lower 3-year OS rate compared to subjects with positive expression (p = 0.04). The loss of HLA class II expression (p = 0.05) and belonging to the intermediate high/high IPI risk group (p = 0.001) independently increased the risk of death. HLA class II expression also retained its prognostic value in patients receiving rituximab; the 3-year OS rate was 65.3 % in patients with positive HLA class II expression versus 29.6 % (p = 0.04) in subjects that had loss of HLA class II expression. To our knowledge, for the first time, the expression of HLA-G protein in DLBCL and its association with the clinical course of the disease was demonstrated. Moreover, the link between losing HLA class II protein expression and poor survival of patients treated with immunochemotherapy was confirmed.

  14. Nodular lymphocyte predominant hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma--endpoints of a spectrum of one disease?

    Directory of Open Access Journals (Sweden)

    Sylvia Hartmann

    Full Text Available In contrast to the commonly indolent clinical behavior of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL, T cell/histiocyte rich large B cell lymphoma (THRLBCL is frequently diagnosed in advanced clinical stages and has a poor prognosis. Besides the different clinical presentations of these lymphoma entities, there are variants of NLPHL with considerable histopathologic overlap compared to THRLBCL. Especially THRLBCL-like NLPHL, a diffuse form of NLPHL, often presents a histopathologic pattern similar to THRLBCL, suggesting a close relationship between both lymphoma entities. To corroborate this hypothesis, we performed gene expression profiling of microdissected tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. In unsupervised analyses, the lymphomas did not cluster according to their entity. Moreover, even in supervised analyses, very few consistently differentially expressed transcripts were found, and for these genes the extent of differential expression was only moderate. Hence, there are no clear and consistent differences in the gene expression of the tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. Based on the gene expression studies, we identified BAT3/BAG6, HIGD1A, and FAT10/UBD as immunohistochemical markers expressed in the tumor cells of all three lymphomas. Characterization of the tumor microenvironment for infiltrating T cells and histiocytes revealed significant differences in the cellular composition between typical NLPHL and THRLBCL cases. However, THRLBCL-like NLPHL presented a histopathologic pattern more related to THRLBCL than NLPHL. In conclusion, NLPHL and THRLBCL may represent a spectrum of the same disease. The different clinical behavior of these lymphomas may be strongly influenced by differences in the lymphoma microenvironment, possibly related to the immune status of the patient at the timepoint of diagnosis.

  15. Clinical implication of genome-wide profiling in diffuse large B-cell lymphoma and other subtypes of B-cell lymphoma

    DEFF Research Database (Denmark)

    Iqbal, Javeed; Joshi, Shantaram; Patel, Kavita N

    2007-01-01

    of Lymphoid Neoplasms (REAL) and World Health Organization (WHO) classifications. These classification methods were based on histological, immunophenotypic and cytogenetic markers and widely accepted by pathologists and oncologists worldwide. During last several decades, great progress has been made...... technology. The genome-wide transcriptional measurement, also called gene expression profile (GEP) can accurately define the biological phenotype of the tumor. In this review, important discoveries made by genome-wide GEP in understanding the biology of lymphoma and additionally the diagnostic and prognostic...

  16. Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies

    Science.gov (United States)

    Kim, Yeong-Jin; Kim, Hee Kyung; Yang, Deok-Hwan; Jung, Shin; Noh, Myung-Giun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2016-01-01

    Abstract This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma. A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL. Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma. PMID:26937937

  17. Renal small B-cell lymphoma with plasmacytic differentiation presenting with monoclonal gammopathy and disseminated intravascular coagulation syndrome

    Directory of Open Access Journals (Sweden)

    Paula de Oliveira Pádua Prestes

    2013-10-01

    Full Text Available Primary renal lymphomas are very rare. However, the kidney may be a site of metastasis, usually from a disseminated aggressive lymphoma. A 58-year-old woman was brought to the medical facility due to acute mental confusion, severe hypotension, septic shock, and signs of disseminated intravascular coagulation. Laboratory tests showed severe leukopenia, renal failure, altered liver function, and elevated serum lactate dehydrogenase levels. Protein electrophoresis revealed hypergammaglobulinemia with a monoclonal peak of IgG lambda. The clinical outcome was fulminant and the patient died less than 24 hours after admission. Autopsy revealed an indolent B-cell lymphoma with extensive plasmacytic differentiation infiltrating the right renal sinus and involving the submandibular and sublingual glands, cervical and peri-aortic lymph nodes, multiple microscopic foci in pituitary and adrenal glands, lung, breast, liver, thyroid, and bone marrow. Numerous IgG4-positive plasma cells were detected by immunohistochemistry although other histological features of IgG4-related disease were missing. There was also extensive hemorrhagic necrosis of the adrenal glands and purulent cystitis, which was probably responsible for the septic shock. The authors concluded that the kidney was most likely the primary site of the indolent lymphoma, as that was the site with the largest tumor mass. Infiltration of other organs was considered as dissemination of the disease. The differential diagnosis with mucosa-associated lymphoid tissue and lymphoplasmacytic lymphoma is discussed.

  18. Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies: A Case Report.

    Science.gov (United States)

    Kim, Yeong-Jin; Kim, Hee Kyung; Yang, Deok-Hwan; Jung, Shin; Noh, Myung-Giun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2016-02-01

    This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma.A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL.Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma.

  19. Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Kristensen, Lasse Sommer; Asmar, Fazila; Dimopoulos, Konstantinos;

    2014-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Improvements in overall survival have been observed with the introduction of rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), however, prognostic markers...

  20. T(14;18)(q32;q21) involving MALT1 and IGH genes occurs in extranodal diffuse large B-cell lymphomas of the breast and testis

    NARCIS (Netherlands)

    Kuper-Hommel, M.J.; Schreuder, M.I.; Gemmink, A.H.; Krieken, J.H. van

    2013-01-01

    Primary B-cell lymphoma of the testis, breast and thyroid are rare and data concerning cytogenetic aberrations at these extranodal sites are scarce. We examined the presence of extranodal marginal zone lymphoma-associated translocations, t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), t(3;14

  1. Interim positron emission tomography scan associated with international prognostic index and germinal center B cell-like signature as prognostic index in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Lanic, Hélène; Mareschal, Sylvain; Mechken, Férial; Picquenot, Jean-Michel; Cornic, Marie; Maingonnat, Catherine; Bertrand, Philippe; Clatot, Florian; Bohers, Elodie; Stamatoullas, Aspasia; Leprêtre, Stéphane; Rainville, Vinciane; Ruminy, Philippe; Bastard, Christian; Tilly, Hervé; Becker, Stéphanie; Vera, Pierre; Jardin, Fabrice

    2012-01-01

    [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is essential to optimize the initial staging and to predict the prognosis of diffuse large B-cell lymphoma (DLBCL). To assess the relationship between the germinal center B cell-like/activated B cell-like (GCB/ABC) classification and PET scan features in DLBCL, 57 cases treated with rituximab and a cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)/CHOP-like regimen were analyzed. The expression profile of 18 GCB/ABC related genes and five genes coding for glucose transporters (GLUTs) was determined from frozen tissues using DASL (cDNA-mediated Annealing, Selection, Ligation and extension) technology. According to the gene expression profile (GEP), 30 cases of DLBCL were classified as GCB subtype (2-year progression-free survival [PFS] 76%) and 27 cases as ABC subtype (2-year PFS 51%, p = 0.03). Using a semiquantitative assessment of the decrease in standard uptake value (SUV) at interim PET performed after 3-4 cycles of chemotherapy, we defined fast (n = 36) and slow (n = 9) metabolic responders. In multivariate analysis, GCB/ABC subtype, age-adjusted international prognostic index (aaIPI) and slow/fast metabolic response were independent variables that predicted outcome. A score incorporating aaIPI, fast/slow metabolic response and GCB/ABC classification was used to define two groups with highly significantly distinct outcomes. Our study suggests that the combination of GEP, aaIPI and interim PET more accurately predicts DLBCL prognosis and is therefore suitable for tailoring therapeutic strategies.

  2. Gastric low-grade MALT lymphoma, high-grade MALT lymphoma and diffuse large B cell lymphoma show different frequencies of trisomy

    NARCIS (Netherlands)

    Hoeve, M A; Gisbertz, I A; Schouten, H C; Schuuring, E; Bot, F J; Hermans, J; Hopman, A; Kluin, P M; Arends, J E; van Krieken, J H

    1999-01-01

    Gastric MALT lymphoma is a distinct entity related to Helicobacter pylori gastritis. Some studies suggest a role for trisomy 3 in the genesis of these lymphomas, but they mainly focused on low-grade MALT lymphoma. Gastric MALT lymphoma, however, comprises a spectrum from low- to high-grade cases. Fu

  3. Primary diffuse large B-cell lymphoma of the corpora cavernosa presented as a perineal mass

    Science.gov (United States)

    Carlos, González-Satué; Ivanna, Valverde Vilamala; Gustavo, Tapia Melendo; Joan, Areal Calama; Javier, Sanchez Macias; Luis, Ibarz Servio

    2012-01-01

    Primary male genital lymphomas may appear rarely in testis, and exceptionally in the penis and prostate, but there is not previous evidence of a lymphoma arising from the corpora cavernosa. We report the first case in the literature of a primary diffuse cell B lymphoma of the corpora cavernosa presented with low urinary tract symptoms, perineal pain and palpable mass. Diagnosis was based on trucut biopsy, histopathological studies and computed tomographic images. PMID:22919138

  4. Hypercalcemia and huge splenomegaly presenting in an elderly patient with B-cell non-Hodgkin's lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Tirgari Farrokh

    2010-10-01

    Full Text Available Abstract Introduction Hypercalcemia is the major electrolyte abnormality in patients with malignant tumors. It can be due to localized osteolytic hypercalcemia or elaboration of humoral substances such as parathyroid hormone-related protein from tumoral cells. In hematological malignancies, a third mechanism of uncontrolled synthesis and secretion of 1-25(OH2D3 from tumoral cells or neighboring macrophages may contribute to the problem. However, hypercalcemia is quite unusual in patients with B-cell non-Hodgkin's lymphoma. Case presentation An 85-year-old Caucasian woman presented with low grade fever, anorexia, abdominal discomfort and fullness in her left abdomen for the last six months. She was mildly anemic and complained of fatigability. She had huge splenomegaly and was hypercalcemic. After correction of her hypercalcemia, she had a splenectomy. Microscopic evaluation revealed a malignant lymphoma. Her immunohistochemistry was positive for leukocyte common antigen, CD20 and parathyroid hormone-related peptide. Conclusion Immunopositivity for parathyroid hormone-related peptide clearly demonstrates that hypersecretion of a parathyroid hormone-like substance from the tumor had led to hypercalcemia in this case. High serum calcium is seen in only seven to eight percent of patients with B-cell non-Hodgkin's lymphoma, apparently due to different mechanisms. Evaluation of serum parathyroid hormone-related protein and 1-25(OH2D3 can be helpful in diagnosis and management. It should be noted that presentation with hypercalcemia has a serious impact on prognosis and survival.

  5. Combinatorial BTK and MALT1 inhibition augments killing of CD79 mutant diffuse large B cell lymphoma.

    Science.gov (United States)

    Nagel, Daniel; Bognar, Miriam; Eitelhuber, Andrea C; Kutzner, Kerstin; Vincendeau, Michelle; Krappmann, Daniel

    2015-12-08

    Survival of activated B cell-subtype (ABC) of diffuse large B cell lymphoma (DLBCL) is driven by chronic B cell receptor (BCR) signaling that activates the canonical NF-κB pathway. Inhibition of BTK by Ibrutinib has been shown to kill ABC DLBCL cells that carry activating mutations in the BCR adaptor CD79. However, mutations in BTK or in downstream components such as CARMA1/CARD11 can render lymphomas Ibrutinib resistant. Therefore, we assessed here the simultaneous inhibition of BTK and the protease MALT1 that acts downstream of CARMA1 and is essential for ABC DLBCL tumor growth. We show that in CD79 mutant cells BTK is a crucial upstream regulator of MALT1, but dispensable in CARMA1 mutant ABC DLBCL. Combined inhibition of BTK by Ibrutinib and MALT1 by S-Mepazine additively impaired MALT1 cleavage activity and expression of NF-κB pro-survival factors. Thereby, combinatorial Ibrutinib and S-Mepazine treatment enhanced killing of CD79 mutant ABC DLBCL cells. Moreover, while expression of oncogenic CARMA1 in CD79 mutant cells conferred Ibrutinib resistance, double mutant cells were still sensitive to MALT1 inhibition by S-Mepazine. Thus, based on the genetic background combinatorial BTK and MALT1 inhibition may improve effectiveness of therapeutic treatment and reduce the chances for the development of drug resistances.

  6. Retrospective study of intravascular large B-cell lymphoma cases diagnosed in Quebec

    Science.gov (United States)

    Brunet, Vanessa; Marouan, Sofia; Routy, Jean-Pierre; Hashem, Mohamed Amin; Bernier, Vincent; Simard, Raynald; Petrella, Tony; Lamarre, Louis; Théorêt, Gilles; Carrier, Christian; Knecht, Hans; Fleury, Isabelle; Pavic, Michel

    2017-01-01

    Abstract Introduction: Intravascular large B-cell lymphoma (IVL) is an extremely rare malignancy, mainly studied through European and Asian series. Due to the low incidence of this condition, our understanding of the clinical presentation as well as the management of IVL relies on a limited number of patients. We report the largest North American study to date on IVL with 29 cases from Quebec hospital diagnosed between 1990 and 2016. The aim of our study is to describe the clinical presentations, diagnostic and staging procedures, therapeutic management and clinical outcomes of IVL patients in our population and compare the disease phenotype to European and Asian series reported. In our cohort, all patients had stage IV IVL at diagnosis, with a median age of 66.7 years (range 47.2–90.8). Clinical presentation was characterized by constitutional symptoms (100%), poor ECOG-PS (100% ≥ 2), cytopenias (93% anemia), and elevated lactate dehydrogenase (97%) and C-reactive protein (96%). Our cohort presented with mainly cutaneous and neurological symptoms. However, neurological involvement (75.9%) was predominant and no “cutaneous variant” was observed; this differs from European literature, where “classical” IVL is reported with mainly cutaneous involvement. Two of our Caucasian patients presented “Asian variant” IVL; this observation is not unusual, as cases of “classical” IVL have been reported in Asians and “Asian variant” IVL has been reported in Europeans. All patients were classified according to their immunophenotypic features in 3 different subgroups (CD5+ or CD5−CD10+, CD5−CD10−, CD5+CD10−) with no difference in outcome. Finally, 62% of our cohort received anthracycline-based chemotherapy and 53% of them achieved a complete response. After a median follow-up of 328 days, OS at 3 years was 42.7% for the entire cohort and 47.4% for the cases with in vivo diagnosis. Conclusion: Unlike European studies on “classical” IVL, our study

  7. In Situ Hepatitis C NS3 Protein Detection Is Associated with High Grade Features in Hepatitis C-Associated B-Cell Non-Hodgkin Lymphomas

    Science.gov (United States)

    Rabiega, Pascaline; Molina, Thierry J.; Charlotte, Frédéric; Lazure, Thierry; Davi, Frédéric; Settegrana, Catherine; Berger, Françoise; Alric, Laurent; Cacoub, Patrice; Terrier, Benjamin; Suarez, Felipe; Sibon, David; Dupuis, Jehan; Feray, Cyrille; Tilly, Hervé; Pol, Stanislas; Deau Fischer, Bénédicte; Roulland, Sandrine; Thieblemont, Catherine; Leblond, Véronique; Carrat, Fabrice; Hermine, Olivier; Besson, Caroline

    2016-01-01

    Hepatitis C Virus (HCV) infection is associated with the B-cell non-Hodgkin lymphomas (NHL), preferentially marginal zone lymphomas (MZL) and diffuse large B-cell lymphomas (DLBCL). While chronic antigenic stimulation is a main determinant of lymphomagenesis in marginal zone lymphomas (MZL), a putative role of HCV infection of B-cells is supported by in vitro studies. We performed a pathological study within the "ANRS HC-13 LymphoC" observational study focusing on in situ expression of the oncogenic HCV non structural 3 (NS3) protein. Lympho-C study enrolled 116 HCV-positive patients with B-NHL of which 86 histological samples were collected for centralized review. Main histological subtypes were DLBCL (36%) and MZL (34%). Almost half of DLBCL (12/26) were transformed from underlying small B-cell lymphomas. NS3 immunostaining was found positive in 17 of 37 tested samples (46%). There was a striking association between NS3 detection and presence of high grade lymphoma features: 12 out of 14 DLBCL were NS3+ compared to only 4 out of 14 MZL (p = 0.006). Moreover, 2 among the 4 NS3+ MZL were enriched in large cells. Remarkably, this study supports a new mechanism of transformation with a direct oncogenic role of HCV proteins in the occurrence of high-grade B lymphomas. PMID:27257992

  8. Gastric infiltration of diffuse large B-cell lymphoma: Endoscopic diagnosis and improvement of lesions after chemotherapy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of the non-Hodgkin's lymphoma (NHL) accounting for about 40% of all NHLs. This is a case report about the endoscopic appearance of a DLBCL with infiltration to the stomach in a 39-year-old female. She had a 6-me history of lumbar and left upper quadrant pain with intermittent episodes of melena. A computer tomograghy (CT) scan showed mural thickening of the gastric antrum. Endoscopic examination revealed multiple gastric ulcers. Definite diagnosis could be made by endoscopic biopsies and the patient had a good response to chemotherapy. This response correlated well with a further endoscopic follow-up. A follow-up endoscopic examination could be considered to evaluate a good response to chemotherapy in DLBCL patients with secondary gastric dissemination.

  9. Routine imaging for diffuse large B-cell lymphoma in first remission is not associated with better survival

    DEFF Research Database (Denmark)

    El-Galaly, Tarec; Jakobsen, Lasse Hjort; Hutchings, Martin

    2015-01-01

    Background: Routine surveillance imaging plays a limited role in detecting recurrent diffuse large B-cell lymphoma (DLBCL), and the value of routine imaging is controversial. The present population-based study compares the post-remission survival of Danish and Swedish DLBCL patients......-two neighbouring countries with comparable treatment guidelines but with completely different traditions for routine surveillance imaging. Methods: Patients enroled in the Danish (LYFO) and Swedish population-based lymphoma registries were included by following criteria: (a) newly diagnosed DLBCL in the period...... (HR 2.3, P 2 (HR 1.8, P = 0.04) at diagnosis were associated with inferior post-remission OS in multivariate Cox analysis, whereas an imaging-based FU strategy (country of FU) was not prognostic. An imaging-based FU strategy also had...

  10. Chemotherapy versus surgery in primary B-cell lymphoma masquerading as Klatskin tumor-a diagnostic and therapeutic dilemma.

    Science.gov (United States)

    Ghose, Abhimanyu; Sethi, Namrata; Li, Guiyuan; Chaudhary, Rekha

    2011-11-01

    Primary lymphoma in the region of the liver bed mimicking hilar cholangiocarcinoma or Klatskin tumor is very rare. A patient presented with obstructive jaundice along with right upper quadrant pain, weight loss, and decreased appetite. Apart from altered liver function, her lactate dehydrogenase was significantly elevated, and imaging studies showed prominent lesion close to the liver bed with localized lymphadenopathy. The diagnosis ultimately reached at by biopsy and immunohistochemical staining was diffuse large B-cell lymphoma. Such cases are very infrequent, but demand awareness. The sooner the diagnosis can be reached by minimally invasive procedures, the earlier chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone can be initiated and laparotomy can be avoided as chemotherapy is the mainstay of treatment, even in the presence of jaundice.

  11. The CXCR4 antagonist plerixafor enhances the effect of rituximab in diffuse large B-cell lymphoma cell lines

    DEFF Research Database (Denmark)

    Reinholdt, Linn; Laursen, Maria Bach; Schmitz, Alexander;

    2016-01-01

    . Accordingly, the fraction of apoptotic/dead cells significantly increased following addition of plerixafor to rituximab treatment. Furthermore, exposure of DLBCL cells to plerixafor resulted in a significant decrease in CXCR4 fluorescence intensity. CONCLUSIONS: Based on our results, implying that the anti......BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with variable clinical outcome, accounting for at least 25-30 % of adult non-Hodgkin lymphomas. Approximately one third of DLBCL patients are not cured by the currently used treatment regimen, R-CHOP. Hence, new treatment......-proliferative/pro-apoptotic effect of rituximab on DLBCL cells can be synergistically enhanced by the CXCR4 antagonist plerixafor, addition of plerixafor to the R-CHOP regimen can be suggested to improve treatment outcome for DLBCL patients....

  12. Frequent somatic hypermutation of the 5' noncoding region of the BCL6 gene in B-cell lymphoma.

    Science.gov (United States)

    Migliazza, A; Martinotti, S; Chen, W; Fusco, C; Ye, B H; Knowles, D M; Offit, K; Chaganti, R S; Dalla-Favera, R

    1995-01-01

    The BCL6 gene encodes a zinc-finger transcription factor and is altered by chromosomal arrangements in its 5' noncoding region in approximately 30% of diffuse large-cell lymphoma (DLCL). We report here that, in 22/30 (73%) DLCL and 7/15 (47%) follicular lymphoma (FL), but not in other tumor types, the BCL6 gene is also altered by multiple (1.4 x 10(-3) -1.6 x 10(-2) per bp), often biallelic, mutations clustering in its 5' noncoding region. These mutations are of somatic origin and are found in cases displaying either normal or rearranged BLC6 alleles indicating their independence from chromosomal rearrangements and linkage to immunoglobulin genes. These alterations identify a mechanism of genetic instability in malignant B cells and may have been selected during lymphomagenesis for their role in altering BCL6 expression. Images Fig. 2 Fig. 4 PMID:8618933

  13. Primary endobronchial marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue: CT findings 7 patients

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Ra Gyoung; Kim, Mi Young; Song, Jae Woo; Chae, Eun Jin; Choi, Chang Min; Jang, Se Jin [University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2013-04-15

    To investigate CT and 1{sup 8F}-fluorodeoxyglucose (1{sup 8F}-FDG) positron-emission tomography/CT findings of primary endobronchial marginal zone B-cell lymphoma of the bronchus-associated lymphoid tissue (BALT). From June 2006 through April 2012, seven patients (six female, one male; age range, 21-61 years; mean age, 49 years) were examined who were pathologically diagnosed with the primary endobronchial marginal zone B-cell lymphoma of BALT. We evaluated the locations and characteristics of the lesions on CT and 1{sup 8F}-FDG-PET/CT scans. The lesions were classified into the following three patterns: 1) solitary intraluminal nodule; 2) several tiny nodular protrusions; and 3) diffuse wall thickening. A solitary intraluminal nodule was observed in four patients (57.1%), several tiny nodular protrusion in two patients (28.6%), and diffuse wall thickening in one patient (14.3%). The lesions were categorized into 3 major locations: confined to the trachea (n 3), confined to the lobar bronchus (n = 2), and diffuse involvement of the trachea and both main bronchi (n = 2). All lesions demonstrated homogeneous iso-attenuation as compared with muscle on pre- and post-enhancement scans. Secondary findings in the lungs (n = 3; 42.9%) included postobstructive lobar atelectasis (n = 1), air trapping (n = 1), and pneumonia (n = 1). On 1{sup 8F}-FDG-PET/CT (n = 5), 4 lesions showed homogeneous uptake with maximum standardized uptake values (mSUV), ranging 2.3-5.7 (mean mSUV: 3.3). One lesion showed little FDG uptake. Primary endobronchial marginal zone B-cell lymphoma of the BALT manifests as three distinct patterns on CT, with the solitary intraluminal nodule presenting as the main pattern. Most lesions demonstrate homogeneous but weak FDG uptake on 1{sup 8F}-FDG-PET/CT.

  14. Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas.

    Science.gov (United States)

    Ruan, J; Shah, B; Martin, P; Schuster, S J

    2016-07-01

    Lenalidomide is an oral immunomodulatory drug with significant activity in indolent B-cell and mantle cell lymphomas. Lenalidomide has a manageable safety profile whether administered as a single agent or in combination with rituximab. The combination of lenalidomide with rituximab, known as the 'R(2)' regimen, enhances efficacy over what has been shown with monotherapy and has demonstrated activity in patients considered resistant to rituximab. Tolerability of these regimens has been consistent among studies. Asymptomatic neutropenia is the most common grade 3/4 adverse event, typically managed by dose interruption, followed by dose reduction once neutrophils have recovered. Nonhematologic toxicities (e.g. fatigue) are generally low-grade, manageable with concomitant treatment, and/or lenalidomide dose modification. More frequent with R(2), immune-related symptoms such as rash and tumor flare are important to recognize as lenalidomide-associated treatment effects in patients with lymphoma who require supportive care and potential dose modifications. Severe tumor flare reactions with painful lymphadenopathy are not typically observed outside of chronic lymphocytic leukemia/small lymphocytic lymphoma. Venous thromboembolism is uncommon in lymphomas, though prophylaxis is recommended. The general safety profile, differences between lenalidomide monotherapy and R(2) treatment, and optimal strategies for managing adverse events are discussed here.

  15. Mediastinal B-Cell Lymphoma Presenting with Jugular-Subclavian Deep Vein Thrombosis as the First Presentation

    Directory of Open Access Journals (Sweden)

    Sherif Ali Eltawansy

    2015-01-01

    Full Text Available Jugular venous thrombosis infrequently could be secondary to malignancy and has seldom been reported secondary to mediastinal large B-cell lymphomas. The postulated mechanisms are mechanical compression that leads to stagnation of blood in the venous system of the neck and/or an increase in the circulating thrombogenic elements that could cause venous thromboembolism as a paraneoplastic phenomenon. We report the case of a middle aged male presenting with right sided neck pain and arm swelling secondary to ipsilateral jugular-subclavian deep vein thrombosis. Investigations revealed it to be secondary to a mediastinal mass shown on CT scan of the chest.

  16. Analysis of survival and prognsis in 409 newly diagnosed patients with diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    文菁菁

    2014-01-01

    Objective To explore the poor prognostic factors of diffuse large B-cell lymphoma(DLBCL).Methods The clinical data of 409 newly diagnosed patients with DLBCL from January 2000 to December 2010 were collected,and the prognostic factors by univariate and multivariate stratification were analyzed.Results Of the 409 DLBCL patients,244 were males and 165 females,the median age was 56(16-89)years old,the median follow-up time was 23(2-108)months.In univariate analysis,

  17. The utility of lactate dehydrogenase in the follow up of patients with diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Basem Magdy William

    2013-06-01

    Full Text Available Background: Serum lactate dehydrogenase is a non-specific marker for lymphoma whose prognostic significance is well established for both indolent and aggressive lymphomas at the time of diagnosis. The performance characteristics of this enzyme in predicting relapse in patients with diffuse large B-cell lymphoma has not been well studied. Methods: This study compared serum lactate dehydrogenase levels in 27 patients with diffuse large B-cell lymphoma who relapsed after sustaining a complete response versus 87 patients who did not relapse. For relapsed patients, the serum lactate dehydrogenase level at relapse was compared with the level three months before (considered baseline. For non-relapsed patients, the last two levels during follow-up were compared. For statistical analysis the T-test was used to compare differences in mean values between groups. The sensitivity, specificity, positive and negative predictive values for serum lactate dehydrogenase in detecting relapse compared to confirmatory imaging were calculated. Results: At relapse, only 33% patients had increases in serum lactate dehydrogenase above the upper limit of normal. The mean increase was 1.2-fold above the upper limit of normal for relapsed vs. 0.83 for those who did not relapse (p-value = 0.59. The mean increase in serum lactate dehydrogenase, from baseline, was 1.1-fold in non-relapsed vs. 1.3 in relapsed patients (p-value = 0.3. The likelihood ratio of relapse was 4.65 for patients who had 1.5-fold increases in serum lactate dehydrogenase above baseline (p-value = 0.03. The sensitivity, specificity, positive and negative predictive values of 1.5-fold increases for detecting relapse, compared to clinical and imaging findings were 0.18, 0.95, 0.55, and 0.79, respectively. Conclusion: A 1.5-fold increase in serum lactate dehydrogenase, over a period of 3 months, is associated with increased likelihood of relapse from diffuse large B-cell lymphoma.

  18. Large B-cell lymphoma arising in cardiac myxoma or intracardiac fibrinous mass: a localized lymphoma usually associated with Epstein-Barr virus?

    Science.gov (United States)

    Aguilar, Cristian; Beltran, Brady; Quiñones, Pilar; Carbajal, Tomas; Vilcapaza, Jorge; Yabar, Alejandro; Segura, Pedro; Quintanilla-Martinez, Leticia; Miranda, Roberto N; Castillo, Jorge J

    2015-01-01

    Primary cardiac neoplasms are rare. However, among them, cardiac myxoma is the most common tumor. In contrast, primary cardiac lymphoma within a cardiac myxoma is extremely rare and might be difficult to diagnose because of non-specific clinical manifestations. We report the case of a previously healthy 52-year-old man who presented with acute onset of transient dysarthria and left hemiplegia. A transthoracic echocardiography showed a 6×2.5-cm solid mass in the left atrium, which was subsequently resected. Histological, immunohistochemical, and molecular analyses revealed an EBV-associated CD30-positive large B-cell lymphoma with anaplastic morphology within a cardiac myxoma and fibrinous material. Staging studies showed no evidence of lymphoma elsewhere. The patient achieved complete remission and is alive 42 months after diagnosis, and did not receive chemotherapy. We discuss the clinical and pathologic features of lymphoma arising in cardiac myxoma or in intra-atrial fibrinoid mass and the potential role of IL-6 in its pathogenesis.

  19. GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests shared genetic susceptibility with diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Karin E Smedby

    2011-04-01

    Full Text Available Non-Hodgkin lymphoma (NHL represents a diverse group of hematological malignancies, of which follicular lymphoma (FL is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (OR(combined  = 0.64, P(combined  = 2 × 10(-21 located 962 bp away from rs10484561 (r(2<0.1 in controls. After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:OR(adjusted  = 0.70, P(adjusted  =  4 × 10(-12; rs10484561:OR(adjusted  = 1.64, P(adjusted  = 5 × 10(-15. Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (OR(combined  = 1.36, P(combined  =  1.4 × 10(-7. Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.

  20. GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests shared genetic susceptibility with diffuse large B-cell lymphoma.

    Science.gov (United States)

    Smedby, Karin E; Foo, Jia Nee; Skibola, Christine F; Darabi, Hatef; Conde, Lucia; Hjalgrim, Henrik; Kumar, Vikrant; Chang, Ellen T; Rothman, Nathaniel; Cerhan, James R; Brooks-Wilson, Angela R; Rehnberg, Emil; Irwan, Ishak D; Ryder, Lars P; Brown, Peter N; Bracci, Paige M; Agana, Luz; Riby, Jacques; Cozen, Wendy; Davis, Scott; Hartge, Patricia; Morton, Lindsay M; Severson, Richard K; Wang, Sophia S; Slager, Susan L; Fredericksen, Zachary S; Novak, Anne J; Kay, Neil E; Habermann, Thomas M; Armstrong, Bruce; Kricker, Anne; Milliken, Sam; Purdue, Mark P; Vajdic, Claire M; Boyle, Peter; Lan, Qing; Zahm, Shelia H; Zhang, Yawei; Zheng, Tongzhang; Leach, Stephen; Spinelli, John J; Smith, Martyn T; Chanock, Stephen J; Padyukov, Leonid; Alfredsson, Lars; Klareskog, Lars; Glimelius, Bengt; Melbye, Mads; Liu, Edison T; Adami, Hans-Olov; Humphreys, Keith; Liu, Jianjun

    2011-04-01

    Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (OR(combined)  = 0.64, P(combined)  = 2 × 10(-21)) located 962 bp away from rs10484561 (r(2)<0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:OR(adjusted)  = 0.70, P(adjusted)  =  4 × 10(-12); rs10484561:OR(adjusted)  = 1.64, P(adjusted)  = 5 × 10(-15)). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (OR(combined)  = 1.36, P(combined)  =  1.4 × 10(-7)). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.

  1. Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells.

    Science.gov (United States)

    Bai, Wenlin; Chen, Yujiao; Sun, Pengling; Gao, Ai

    2016-01-01

    Titanium dioxide (TiO2) nanoparticles (TNPs) are manufactured worldwide for a wide range of applications and the toxic effect of TNPs on biological systems is gaining attention. Autophagy is recognized as an emerging toxicity mechanism triggered by nanomaterials. MicroRNA 34a (miR34a) acts as a tumor suppressor gene by targeting many oncogenes, but how it affects autophagy induced by TNPs is not completely understood. Here, we observed the activation of TNP-induced autophagy through monodansylcadaverine staining and LC3-I/LC3-II conversion. Meanwhile, the transmission electron microscope ultrastructural analysis showed typical morphological characteristics in autophagy process. We detected the expression of miR34a and B-cell lymphoma/leukemia-2 (Bcl-2). In addition, the underlying mechanism of TNP-induced autophagy was performed using overexpression of miR34a by lentivirus vector transfection. Results showed that TNPs induced autophagy generation evidently. Typical morphological changes in the process of autophagy were observed by the transmission electron microscope ultrastructural analysis and LC3-I/LC3-II conversion increased significantly in TNP-treated cells. Meanwhile, TNPs induced the downregulation of miR34a and increased the expression of Bcl-2. Furthermore, overexpressed miR34a decreased the expression of Bcl-2 both in messenger RNA and protein level, following which the level of autophagy and cell death rate increased after the transfected cells were incubated with TNPs for 24 hours. These findings provide the first evidence that overexpressed miR34a enhanced TNP-induced autophagy and cell death through targeted downregulation of Bcl-2 in BEAS-2B cells.

  2. Somatic mutation of EZH2 (Y641) in follicular and diffuse large B-cell lymphomas of germinal center origin | Office of Cancer Genomics

    Science.gov (United States)

    Morin et al. describe recurrent somatic mutations in EZH2, a polycomb group oncogene. The mutation, found in the SET domain of this gene encoding a histone methyltransferase, is found only in a subset of lymphoma samples. Specifically, EZH2 mutations are found in about 12% of follicular lymphomas (FL) and almost 23% of diffuse large B-cell lymphomas (DLBCL) of germinal center origin. This paper goes on to demonstrate that altered EZH2 proteins, corresponding to the most frequent mutations found in human lymphomas, have reduced activity using in vitro histone methylation assays.

  3. Cerebral venous thrombosis in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma during induction chemotherapy with l-asparaginase: The GRAALL experience.

    Science.gov (United States)

    Couturier, Marie-Anne; Huguet, Françoise; Chevallier, Patrice; Suarez, Felipe; Thomas, Xavier; Escoffre-Barbe, Martine; Cacheux, Victoria; Pignon, Jean-Michel; Bonmati, Caroline; Sanhes, Laurence; Bories, Pierre; Daguindau, Etienne; Dorvaux, Véronique; Reman, Oumedaly; Frayfer, Jamile; Orvain, Corentin; Lhéritier, Véronique; Ifrah, Norbert; Dombret, Hervé; Hunault-Berger, Mathilde; Tanguy-Schmidt, Aline

    2015-11-01

    Central nervous system (CNS) thrombotic events are a well-known complication of acute lymphoblastic leukemia (ALL) induction therapy, especially with treatments including l-asparaginase (l-ASP). Data on risk factors and clinical evolution is still lacking in adult patients. We report on the clinical evolution of 22 CNS venous thrombosis cases occurring in 708 adults treated for ALL or lymphoblastic lymphoma (LL) with the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-induction protocol, which included eight L-ASP (6,000 IU/m(2) ) infusions. The prevalence of CNS thrombosis was 3.1%. CNS thrombosis occurred after a median of 18 days (range: 11-31) when patients had received a median of three l-ASP injections (range: 2-7). Patients with CNS thrombosis exhibited a median antithrombin (AT) nadir of 47.5% (range: 36-67%) at Day 17 (range: D3-D28), and 95% of them exhibited AT levels lower than 60%. There were no evident increase in hereditary thrombotic risk factors prevalence, and thrombosis occurred despite heparin prophylaxis which was performed in 90% of patients. Acquired AT deficiency was frequently detected in patients with l-ASP-based therapy, and patients with CNS thrombosis received AT prophylaxis (45%) less frequently than patients without CNS thrombosis (83%), P = 0.0002). CNS thrombosis was lethal in 5% of patients, while 20% had persistent sequelae. One patient received all planned l-ASP infusions without recurrence of CNS thrombotic whereas l-ASP injections were discontinued in 20 patients during the management of thrombosis without a significant impact on overall survival (P = 0.4).

  4. Treatment of childhood T-cell lymphoblastic lymphoma according to the strategy for acute lymphoblastic leukaemia, without radiotherapy: long term results of the EORTC CLG 58881 trial.

    Science.gov (United States)

    Uyttebroeck, Anne; Suciu, Stefan; Laureys, Geneviève; Robert, Alain; Pacquement, Hélène; Ferster, Alina; Marguerite, Geneviève; Mazingue, Françoise; Renard, Marleen; Lutz, Patrick; Rialland, Xavier; Mechinaud, Françoise; Cavé, Hélène; Baila, Liliana; Bertrand, Yves

    2008-04-01

    From June 1989 through to November 1998, 121 children with newly diagnosed T-cell lymphoblastic lymphoma (T-LBL) were included in the EORTC 58881 trial conducted by the Children's Leukaemia Group. The therapy regimen was based on a Berlin-Frankfurt-Munster protocol, for a total duration of 24 months. Cranial irradiation, prophylactic cranial and local, was omitted, even for patients with central nervous involvement at diagnosis. In total, 119 patients were evaluable. The median follow-up was 6.7 years. The overall event-free survival (EFS) rate at 6 years was 77.5% (standard error (SE)=4%). Median time of relapse was 1 year after complete remission (range 0.2-5.9 years). Only two (1.8%) patients had an isolated central nervous system relapse. For patients with complete response (n=16) to the 7-day prephase, the EFS rate at 6 years was 100% versus 14% (P<0.001) for patients with no response (n=7). Overall survival rate at 6 years was 86% (SE=3%). An intensive acute lymphoblastic leukaemia type chemotherapy regimen without irradiation leads to a high cure and survival rate in childhood T-LBL without an increased CNS recurrence. This suggests that prophylactic cranial irradiation can safely be omitted. Response to the prephase appeared to be a strong prognostic factor for EFS.

  5. Spontaneous Remission of an Untreated, MYC and BCL2 Coexpressing, High-Grade B-Cell Lymphoma: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    D. Alan Potts

    2017-01-01

    Full Text Available Non-Hodgkin lymphomas (NHL are a heterogeneous group of hematologic malignancies typically treated with multiagent chemotherapy. Rarely, spontaneous remissions can be observed, particularly in more indolent subtypes. The prognosis of aggressive NHL can be predicted using clinical and histopathologic factors. In aggressive B-cell NHL, the importance of MYC and BCL2 proto-oncogene coexpression (as assessed by immunohistochemistry and high-grade histologic features are particularly noteworthy. We report a unique case of spontaneous remission in a patient with an aggressive B-cell NHL which harbored high-risk histopathologic features, including MYC protein expression at 70–80%, BCL2 protein expression, and morphologic features suggestive of high-grade B-cell lymphoma, NOS (formerly B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma [BCLU]. After undergoing a biopsy to confirm this diagnosis, he opted to forego curative-intent chemotherapy. The single, yet relatively large area of involvement noted on 18F-fluorodeoxyglucose positron emission tomography-computed tomography steadily resolved on subsequent follow-up studies. He remained without evidence of recurrence one year later, having never received treatment. This case emphasizes the potential for spontaneous remission in NHL and demonstrates that this phenomenon can be observed despite contemporary high-risk histopathologic features.

  6. Chemo-sensitivity in a panel of B-cell precursor acute lymphoblastic leukemia cell lines, YCUB series, derived from children.

    Science.gov (United States)

    Goto, Hiroaki; Naruto, Takuya; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Fujii, Hisaki; Yokota, Shumpei; Komine, Hiromi

    2009-10-01

    Sensitivity to 10 anticancer drugs was evaluated in 6 childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines. Authenticity of newly established cell lines was confirmed by genomic fingerprinting. The line YCUB-5R established at relapse was more resistant to 4-hydroperoxy-cyclophosphamide, cytarabine, L-asparaginase, topotecan, fludarabine, and etoposide than YCUB-5 from the same patient at diagnosis. Of the drugs tested, etoposide and SN-38 (irinotecan) showed highest efficacy in the panel, with 50% growth inhibition at 0.22-1.8 microg/ml and 0.57-3.6 ng/ml, respectively. This cell line panel offers an in vitro model for the development of new therapies for childhood BCP-ALL.

  7. Epigenetic remodeling in B-cell acute lymphoblastic leukemia occurs in two tracks and employs embryonic stem cell-like signatures.

    Science.gov (United States)

    Lee, Seung-Tae; Muench, Marcus O; Fomin, Marina E; Xiao, Jianqiao; Zhou, Mi; de Smith, Adam; Martín-Subero, José I; Heath, Simon; Houseman, E Andres; Roy, Ritu; Wrensch, Margaret; Wiencke, John; Metayer, Catherine; Wiemels, Joseph L

    2015-03-11

    We investigated DNA methylomes of pediatric B-cell acute lymphoblastic leukemias (B-ALLs) using whole-genome bisulfite sequencing and high-definition microarrays, along with RNA expression profiles. Epigenetic alteration of B-ALLs occurred in two tracks: de novo methylation of small functional compartments and demethylation of large inter-compartmental backbones. The deviations were exaggerated in lamina-associated domains, with differences corresponding to methylation clusters and/or cytogenetic groups. Our data also suggested a pivotal role of polycomb and CTBP2 in de novo methylation, which may be traced back to bivalency status of embryonic stem cells. Driven by these potent epigenetic modulations, suppression of polycomb target genes was observed along with disruption of developmental fate and cell cycle and mismatch repair pathways and altered activities of key upstream regulators.

  8. Pathogenetic, Clinical, and Prognostic Features of Adult t(4;11(q21;q23/MLL-AF4 Positive B-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    F. Marchesi

    2011-01-01

    Full Text Available Translocation t(4;11(q21;q23 leading to formation of MLL-AF4 fusion gene is found in about 10% of newly diagnosed B-cell acute lymphoblastic leukemia (ALL in adult patients. Patients expressing this chromosomal aberration present typical biological, immunophenotypic, and clinical features. This form of leukemia is universally recognized as high-risk leukemia and treatment intensification with allogeneic hematopoietic stem cell transplantation (HSCT in first complete remission (CR could be a valid option to improve prognosis, but data obtained from the literature are controversial. In this review, we briefly describe pathogenetic, clinical, and prognostic characteristics of adult t(4;11(q21;q23/MLL-AF4 positive ALL and provide a review of the clinical outcome reported by the most important cooperative groups worldwide.

  9. An Unusual Case of Marginal Zone B-Cell Lymphoma Arising in the Breast - Its Diagnosis and the Role of Radiotherapy in its Management.

    Science.gov (United States)

    Rock, Kathy; Rangaswamy, Guhan; O'Sullivan, Siobhra; Coffey, Jerome

    2011-10-01

    BACKGROUND: Primary lymphoma of the breast accounts for 0.04-0.5% of all breast malignancies and approximately 1% of all extranodal lymphomas. For stage IE node-negative disease, involved field radiotherapy is recommended except for very young women in whom the risk of breast cancer is a concern. The rate of complete response for limited stage extranodal marginal B-cell lymphoma is in excess of 90%. CASE REPORT: We report the case of a 62-year-old lady who presented with a unilateral painless palpable right breast lump. She subsequently underwent a trucut biopsy of the lesion. The histology revealed a low-grade B-cell non-Hodgkin's lymphoma (NHL). Immunohistochemistry showed that more than 95% of the cells were B cells which were CD 20+/CD 45+ and BC L6+. This confirmed the diagnosis of marginal zone lymphoma. Staging work-up was negative for distant metastases. Serum alkaline phosphatase and lactate dehydrogenase were normal. The patient had no 'B' symptoms. Her final diagnosis was clinical stage IAE NHL, and she was referred for curative radiotherapy. CONCLUSION: Radiation treatment is a safe and extremely effective modality of treatment for early stage I marginal zone B-cell lymphomas of the breast.

  10. An Unusual Case of Marginal Zone B-Cell Lymphoma Arising in the Breast - Its Diagnosis and the Role of Radiotherapy in its Management.

    LENUS (Irish Health Repository)

    Rock, Kathy

    2011-10-01

    BACKGROUND: Primary lymphoma of the breast accounts for 0.04-0.5% of all breast malignancies and approximately 1% of all extranodal lymphomas. For stage IE node-negative disease, involved field radiotherapy is recommended except for very young women in whom the risk of breast cancer is a concern. The rate of complete response for limited stage extranodal marginal B-cell lymphoma is in excess of 90%. CASE REPORT: We report the case of a 62-year-old lady who presented with a unilateral painless palpable right breast lump. She subsequently underwent a trucut biopsy of the lesion. The histology revealed a low-grade B-cell non-Hodgkin\\'s lymphoma (NHL). Immunohistochemistry showed that more than 95% of the cells were B cells which were CD 20+\\/CD 45+ and BC L6+. This confirmed the diagnosis of marginal zone lymphoma. Staging work-up was negative for distant metastases. Serum alkaline phosphatase and lactate dehydrogenase were normal. The patient had no \\'B\\' symptoms. Her final diagnosis was clinical stage IAE NHL, and she was referred for curative radiotherapy. CONCLUSION: Radiation treatment is a safe and extremely effective modality of treatment for early stage I marginal zone B-cell lymphomas of the breast.

  11. Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Visco, C; Xu-Monette, Z Y; Miranda, R N

    2012-01-01

    Gene expression profiling (GEP) has stratified diffuse large B-cell lymphoma (DLBCL) into molecular subgroups that correspond to different stages of lymphocyte development-namely germinal center B-cell like and activated B-cell like. This classification has prognostic significance, but GEP...... on formalin-fixed, paraffin-embedded tissue samples. Sections were stained with antibodies reactive with CD10, GCET1, FOXP1, MUM1 and BCL6 and cases were classified following a rationale of sequential steps of differentiation of B cells. Cutoffs for each marker were obtained using receiver...

  12. High expression of CD40 on B-cell precursor acute lymphoblastic leukemia blasts is an independent risk factor associated with improved survival and enhanced capacity to up-regulate the death receptor CD95

    NARCIS (Netherlands)

    A. Troeger (Anja); L. Glouchkova (Ludmila); B. Ackermann (Birgit); G. Escherich (Gabriele); R. Meisel (Roland); H. Hanenberg (Helmut); M.L. den Boer (Monique); R. Pieters (Rob); G.E. Janka-Schaub (Gritta); U. Goebel (Ulrich); H.J. Laws; D. Dilloo (Dagmar)

    2008-01-01

    textabstractCD40 and CD27, members of the tumor necrosis factor receptor (TNFR) family, are critical regulators of lymphocyte growth and differentiation. In B-cell precursor acute lymphoblastic leukemia (BCP-ALL), we prospectively assessed the impact of CD40 and CD27 on outcome in 121 children treat

  13. VH1-44 gene usage defines a subset of canine B-cell lymphomas associated with better patient survival.

    Science.gov (United States)

    Chen, Hsiao-Wei; Small, George W; Motsinger-Reif, Alison; Suter, Steven E; Richards, Kristy L

    2014-02-15

    The use of specific immunoglobulin heavy chain variable region (VH) genes has been associated with increased patient survival in human B-cell lymphomas (hBCL). Given the similarity of human and canine BCL (cBCL) in morphology and clinical treatment, we examined the choice of VH in cBCL and determined whether VH gene selection was a distinct feature associated with survival time in dogs. VH gene selection and mutational status in 52 cBCL, including 29 diffuse large B-cell lymphomas (cDLBCL, the most common subtype of cBCL), were analyzed by comparison with the 80 published canine germline VH gene sequences. We further examined the prognostic impact of the subgroups defined by these features on canine survival. We found that VH1-44 was preferentially expressed in the majority of the 52 cBCLs (60%) as well as in the majority of the cDLBCL subset (59%). VH1-44 gene expression was associated with a statistically better overall survival (p=0.039) in cBCL patients, as well as in the cDLBCL subset of patients (p=0.038). These findings suggest that VH gene selection in cBCL is not random and may therefore have functional implications for cBCL lymphomagenesis, in addition to being a useful prognostic biomarker.

  14. Bone marrow large B cell lymphoma bearing cyclin D3 expression: clinical, morphologic, immunophenotypic, and genotypic analyses of seven patients.

    Science.gov (United States)

    Watanuki, Jyuri; Hatakeyama, Kinta; Sonoki, Takashi; Tatetsu, Hiro; Yoshida, Katsuhiko; Fujii, Soichiro; Mizutani, Minoru; Abo, Toru; Kurimoto, Miwa; Matsuoka, Hiroshi; Matsuno, Fumihiko; Nakakuma, Hideki

    2009-09-01

    We report seven large B cell lymphoma patients showing the involvement of tumor cells with cyclin D3 (CCND3) expression in bone marrow (BM) at the initial diagnosis. All patients presented with B symptoms, splenomegaly, and anemia/thrombocytopenia lacking hemophagocytosis in the BM. Five of the seven patients had suffered from immunological diseases or cancers. The tumor cells were divided into those with a lymphoplasmacytoid or blastoid appearance. Six cases were confirmed to express CD5 antigen on tumor cells. Three cases presented a chromosomal translocation between CCND3 and the immunoglobulin heavy chain (IGH) loci, t(6;14)(p21;q32). Three and two cases showed unmutated and mutated sequences of the variable region of IGH (VH), respectively, and one case showed deletion of an entire segment of VH. Two cases with t(6;14)(p21;q32) showed an unmutated VH sequence and chromosomal translocation within the switch region of IGH. Further studies are required to determine whether CCND3 expression is associated with a unique subset of diffuse large B cell lymphoma.

  15. Fcγ receptor IIIA polymorphisms and efficacy of rituximab therapy on Chinese diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wei; WANG Xuan; Li Jian; DUAN Ming-hui; ZHOU Dao-bin

    2010-01-01

    Background Rituximab is used extensively in combination with chemotherapy to cure non-Hodgkin's lymphoma (NHL), and not only accelerates short-term improvement, but also prolongs patient survival and decreases relapse. The aim of this study was to evaluate the impact of Fcγ receptor IIIA (FcγRIIIA) gene polymorphisms on the response to rituximab therapy for newly diagnosed B-cell lymphomas. Methods Patients with newly diagnosed histologically-proven CD20-positive B-cell lymphoma were eligible for the study. All of the patients received rituximab combined with chemotherapy (CHOP). The FcγRIIIA type was analyzed by PCR. The initial efficacy was assessed after 6 cycles and the long-term survival was determined. Results Thirty-four patients were recruited between October 2005 and April 2006. The FcγRIIIA distribution was as follows: 11 patients were W, 5 were FF, and 18 were VF. After a median of 6 cycles (range 4-8) of rituximab combined chemotherapy, the overall response rate was 79% (82% in the VV group, 83% in the VF group, and 60% in the FF group; P=0.04). After a median follow-up time of 37 months (range 34-41), there were 12 relapses among 27 responders (44%); 5 of 9 patients (5/9) in the VV group, 5 of 15 patients (33%) in the VF group, and 2 of 3 patients (2/3) in the FF group (P=0.21). The 1-year overall survival in the VV, FF, and VF groups was 80%, 60%, and 80%, respectively, and the 3-year overall survival was 58%, 40%, and 69%, respectively (P=0.08). After analysis by COX regression, only the international prognosis index and response to initial treatment were significantly related to overall survival. Conclusions The distribution of FcγRIIIA polymorphisms in this B-cell lymphoma population shows that VF is most frequently expressed, followed by VV and FF. Patients with the FcγRIIIA VV and VF types are more sensitive to the initial treatment of rituximab combined with chemotherapy and have superior long-term survival compared with those with FF

  16. ALK-positive diffuse large B-cell lymphoma: two more cases and a brief literature review.

    Science.gov (United States)

    Rudzki, Zbigniew; Rucińska, Małgorzata; Jurczak, Wojciech; Skotnicki, Aleksander B; Maramorosz-Kurianowicz, Magdalena; Mruk, Andrzej; Piróg, Krystyna; Utych, Graźyna; Bodzioch, Piotr; Srebro-Stariczyk, Maria; Włodarska, Iwona; Stachura, Jerzy

    2005-01-01

    Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare, recently defined tumor distinct in many aspects from ALK-positive anaplastic large cell lymphoma (ALCL). We present two additional cases of ALK+DLBCL recently diagnosed in our department and a review of literature. A 48-year old man presented with a large upper neck mass growing slowly over 18 months. Histologically the tumor was diagnosed as an ALK-positive diffuse large B-cell lymphoma. with plasmablastic features. Large, frequently intrasinusoidal tumor cells expressed CD138, EMA, weakly IgA and kappa, but were negative for other B-cell markers, T-cell markers and CD30. The ALK staining was cytoplasmic with the increased intensity in the Golgi area. At the diagnosis the patient manifested with the stage IIIB. Three courses of CHOP resulted in partial and only transient remission. The patient died of massive bleeding from his decomposing tumor 3 months after the diagnosis. A 49-year old man complaining of abdominal pain revealed abdominal lymphadenomegaly and a gastric infiltrate, involving the deep portions of the gastric wall. The tumor showed immunoblastic/anaplastic morphology, with some Reed-Sternberg-like cells positive for ALK. ALK immunostaining was cytoplasmic, weak in a routine immunostain, enhanced with double (proteinase + pressure cooker) antigen retrieval. FISH was consistent with the t(2;5)/nucleophosmin(NPM)-ALK rearrangement. The tumor demonstrated similar "null" B/T phenotype with positivity for IgA, lambda, EMA and LCA. The patient (stage IVB) currently undergoes chemotherapy. ALK-positive DLBCL affects mostly middle-aged men, shows generally poor but stage-dependent prognosis (at least 60% mortality rate), presents typically as a lymph node-based disseminated disease, and very rarely involves the bone marrow. Genetic studies showed that the majority of ALK+DLBCL cases are characterized by the clathrin (CLTC)-ALK fusion and in a few cases the NPM

  17. Down-regulation of BLIMP1α by the EBV oncogene, LMP-1, disrupts the plasma cell differentiation program and prevents viral replication in B cells: implications for the pathogenesis of EBV-associated B-cell lymphomas.

    Science.gov (United States)

    Vrzalikova, Katerina; Vockerodt, Martina; Leonard, Sarah; Bell, Andrew; Wei, Wenbin; Schrader, Alexandra; Wright, Kenneth L; Kube, Dieter; Rowe, Martin; Woodman, Ciaran B; Murray, Paul G

    2011-06-02

    An important pathogenic event in Epstein-Barr virus (EBV)-associated lymphomas is the suppression of virus replication, which would otherwise lead to cell death. Because virus replication in B cells is intimately linked to their differentiation toward plasma cells, we asked whether the physiologic signals that drive normal B-cell differentiation are absent in EBV-transformed cells. We focused on BLIMP1α, a transcription factor that is required for plasma cell differentiation and that is inactivated in diffuse large B-cell lymphomas. We show that BLIMP1α expression is down-regulated after EBV infection of primary germinal center B cells and that the EBV oncogene, latent membrane protein-1 (LMP-1), is alone capable of inducing this down-regulation in these cells. Furthermore, the down-regulation of BLIMP1α by LMP-1 was accompanied by a partial disruption of the BLIMP1α transcriptional program, including the aberrant induction of MYC, the repression of which is required for terminal differentiation. Finally, we show that the ectopic expression of BLIMP1α in EBV-transformed cells can induce the viral lytic cycle. Our results suggest that LMP-1 expression in progenitor germinal center B cells could contribute to the pathogenesis of EBV-associated lymphomas by down-regulating BLIMP1α, in turn preventing plasma cell differentiation and induction of the viral lytic cycle.

  18. Bilateral Facial Nerve Palsy in Acute B Cell Lymphoblastic Leukemia: A Case Report and Review of the Literature.

    Science.gov (United States)

    Sen, Shiraj; Gupta, Arjun; Friedman, Paul; Naina, Harris V

    2016-06-01

    Acute lymphoblastic leukemia (ALL) is a haematological malignancy that can involve the central nervous system (CNS). Less than 10 % of patients with ALL have CNS involvement at presentation. The cranial nerve most commonly affected is cranial nerve VII although bilateral involvement is rare. Management and outcomes of these patients are not well understood. Moreover bilateral Bells palsy as a presenting symptom of ALL is extremely uncommon. We report a very unusual presentation of ALL with bilateral facial nerve palsy, and discuss the management strategies and outcomes for patients with ALL that present with cranial nerve palsies.

  19. Retrospective monitoring of minimal residual disease using hairpin-shaped clone specific primers in B-cell lymphoma affected dogs.

    Science.gov (United States)

    Gentilini, Fabio; Turba, Maria E; Forni, Monica

    2013-06-15

    Lymphoma is one of the most common forms of cancer in dogs as it is in humans but, unlike humans, the cure rates in canines are still very low. Despite the fact that high grade B-cell lymphomas are considered to be chemotherapy responsive, almost all treated dogs ultimately relapse and die due to the residual malignant lymphocytes, namely minimal residual disease (MRD). It would be extremely valuable for clinicians to detect, monitor and quantify MRD for risk group stratification, effective treatment intervention and outcome prediction. The PCRs targeting the Ig gene rearrangements constitute one of the most reliable tools to this end. We have recently validated a method which exploits hairpin-shaped primers for quantifying MRD. In the present study, that method is conveniently used for retrospectively monitoring MRD in the peripheral blood of 8 dogs diagnosed with B-cell lymphoma who underwent chemotherapy. All dogs attained complete remission. The median disease-free interval was 254.5 days (range 63-774) while the median survival time was 313.5 days (range 143-817 days). At admission, all dogs, except one which had already been treated with prednisone, had circulating neoplastic cells. All dogs attained complete remission (CR) which was almost always matched with a complete MRD response. The persistence of MRD despite apparent CR indicated a worse prognosis and a short duration of CR. Finally, the relapse is consistently anticipated by the reappearance of MRD in the peripheral blood. The study confirmed the suitability of an MRD monitoring assay as a clinical decision-making tool.

  20. C-MYC and BCL2 translocation frequency in diffuse large B-cell lymphomas: A study of 97 patients

    Directory of Open Access Journals (Sweden)

    Bahar Akkaya

    2016-01-01

    Full Text Available Purpose: Diffuse large B-cell lymphoma (DLBCL is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. MYC and BCL2 rearrangements have been reported in a proportion of DLBCLs, where they may be associated with an adverse clinical outcome. The aim of this study was to determine the frequency of MYC and BCL2 translocations in DLBCL and assess the prognostic impact in DLBCL patients. Materials and Methods:   In the present study, we evaluated the expression patterns of CD 10, BCL6, and MUM 1 by immunohistochemistry in 121 cases with DLBCL in tissue microarray (TMA: 62 cases in germinal center B-cells (GCBs; and 59 cases in activated B-cells (ABCs of which 60 were females and 61 were males. MYC and BCL2 rearrangements were investigated by interphase fluorescence in situ hybridization on TMAs in 97 DLBCLs. Result: MYC rearrangements were observed in 11 of 97 cases. There was no association with other clinical features, including age, sex, and nodal/extranodal disease. MYC rearrangement was associated with significantly worse overall survival (P < 0.01. BCL2 rearrangements were observed in 14 of 97 cases. There was no association with other clinical features including age and sex. BCL2 rearrangement had a worse outcome (P < 0.01. MYC and BCL2 rearrangements were observed in 3 of 97 cases with the age of  53 (female, 53, 63 years old, respectively, died in 24, 18, and 35 months after the diagnosis. Two cases had primary nodal and one case primary extranodal presentations. All these patients had stage IV disease. Conclusion: We concluded that C-MYC and BCL2 may contribute to aggressive transformation, and more mechanism-based therapy should be explored. Targeted therapies involving these rearrangements and its associated pathways may change the fate of DLBCLs. Analysis of MYC gene rearrangement along with BCL2 is critical in the identification of high-risk patients with poor prognosis.

  1. Diagnosis and therapy of primary lung diffuse large B cell lymphoma: a case report%原发性肺大B细胞淋巴瘤诊断治疗一例报道

    Institute of Scientific and Technical Information of China (English)

    Lei Zhou; Li Duan; Min Hu

    2009-01-01

    Objective: We studied the diagnosis and therapy of primary lung diffuse large B cell lymphoma (DLBCL). Meth-ods: Analysis the clinical manifestations, pathologic character and immunohistochemical character of one tung diffuse B cell lymphoma patent. Results: In visual observation, it's a gray irregular Iobulated mass, section was gray, fish-like, and number of necrotic foci. Observed under the microscope, subepithelial respiratory center oocyte-like cells diffuse proliferative, infiltra-tion in lung tissue. Immunohistochemistry: CDJ0 (+), CD790 (+), CD3 (-), CD45RO (-), PCK (-). Conclusion: Diffuse large B cell lymphoma is the most common subtype in non-Hodgkin lymphoma, but the primary lung diffuse large B cell lymphoma is rare. This disease is lack of typical clinical manifestations, so easily misdiagnosed. The diagnosis of diffuse large B cell lymphoma should be based on pathology and immunohistochemistry.

  2. Expression of PD-1 (CD279) and FoxP3 in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Ahearne, Matthew J; Bhuller, Kaljit; Hew, Roger; Ibrahim, Hazem; Naresh, Kikkeri; Wagner, Simon D

    2014-09-01

    The role of the microenvironment in high-grade lymphoma is not well defined. In this report, we employ immunohistochemistry to characterise programmed death-1 (PD-1/CD279) and FoxP3 expression in 70 cases of diffuse large B-cell lymphoma (DLBCL). PD-1 is a surface marker characteristic of follicular helper T-cells whilst FoxP3 is characteristic of Tregs. We demonstrate variable infiltration with CD4(+) T-cells (50 % of all lymph node cells) and PD-1(hi) cells (0.1 to 1.5 % of all cells). CD4(+) T-cells can be distributed in clusters or more diffusely and PD-1(hi) cells, but not FoxP3(+) cells, are found in rosettes around lymphoma cells. Cases with high CD4(+) T-cell numbers tended to have higher numbers of both PD-1(hi) and FoxP3(+) cells. Cases with total CD4(+) T-cell, PD-1(hi) and FoxP3(+) numbers above the median associate with better clinical outcome. Overall, we demonstrate that infiltration by CD4(+) T-cells, including both FoxP3(+) and PD-1(hi) subsets, correlates with prognosis in DLBCL. In distinction to previous reported series, patients (91 %) were treated with rituximab-containing regimens, suggesting that the effects of CD4+ T-cell infiltration are maintained in the rituximab era. This work suggests that determinants of total CD4(+) T-cell infiltration, either molecular characteristics of the lymphoma or the patients' immune system, and not individual T-cell subsets, correlate with clinical outcome.

  3. Double-hit BCL2/MYC translocations in a consecutive cohort of patients with large B-cell lymphoma - a single centre's experience

    DEFF Research Database (Denmark)

    Pedersen, Mette Ø; Gang, Anne O; Poulsen, Tim S;

    2012-01-01

    Concurrent BCL2 and MYC translocations, so called double hit (DH), are a rare finding in large B-cell lymphoma (LBCL). Based on data from retrospective series, DH has been correlated with aggressive clinical behaviour and poor outcome. We conducted a consecutive study of DH incidence and correlat......Concurrent BCL2 and MYC translocations, so called double hit (DH), are a rare finding in large B-cell lymphoma (LBCL). Based on data from retrospective series, DH has been correlated with aggressive clinical behaviour and poor outcome. We conducted a consecutive study of DH incidence...

  4. Anomalous expression of Thy1 (CD90) in B-cell lymphoma cells and proliferation inhibition by anti-Thy1 antibody treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ishiura, Yoshihito [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kotani, Norihiro, E-mail: kotani@kochi-u.ac.jp [CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kochi System Glycobiology Center, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); Yamashita, Ryusuke [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Yamamoto, Harumi [Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida Shimo-Adachi, Sakyo, Kyoto 606-8501 (Japan); Kozutsumi, Yasunori [CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida Shimo-Adachi, Sakyo, Kyoto 606-8501 (Japan); Honke, Koichi [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kochi System Glycobiology Center, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan)

    2010-05-28

    The anti-CD20 monoclonal antibody (Ab) rituximab is accepted to be an effective therapeutic Ab for malignant B-cell lymphoma; however, discovery of other cell surface antigens is required for the option of antibody medicine. Considering that many tumor-associated antigens are glycans, we have searched glycoconjugates for the candidate antigens that therapeutic Abs target. To this end, we first focused on the difference in the glycogenes expression in terms of Epstein-Barr virus (EBV) infection of a Burkitt's lymphoma cell line, Akata. Using DNA array, flow cytometry and Western blotting, we found that Thy1 was highly expressed in EBV-positive Akata cells. Subsequently, Thy1 was found to be expressed in other B-cell lymphoma cell lines: BJAB, MutuI, and MutuIII, irrespective of EBV infection. Treatment of these cells with an anti-Thy1 monoclonal antibody inhibited proliferation more strongly than the therapeutic Ab rituximab. The B-cell lymphoma cell lines were classified based on the extent of the proliferation inhibition, which was not correlated with the expression level of Thy1. It is suggested that stable residence of receptor tyrosine kinases in lipid rafts sustains cell growth in B-cell lymphoma cells.

  5. Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

    NARCIS (Netherlands)

    Machiela, Mitchell J; Lan, Qing; Slager, Susan L; Vermeulen, Roel C H; Teras, Lauren R; Camp, Nicola J; Cerhan, James R; Spinelli, John J; Wang, Sophia S; Nieters, Alexandra; Vijai, Joseph; Yeager, Meredith; Wang, Zhaoming; Ghesquières, Hervé; McKay, James; Conde, Lucia; de Bakker, Paul I W; Cox, David G; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R; De Roos, Anneclaire J; Brooks-Wilson, Angela R; Giles, Graham G; Melbye, Mads; Gu, Jian; Jackson, Rebecca D; Kane, Eleanor; Purdue, Mark P; Vajdic, Claire M; Albanes, Demetrius; Kelly, Rachel S; Zucca, Mariagrazia; Bertrand, Kimberly A; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M; Link, Brian K; Novak, Anne J; Dogan, Ahmet; Asmann, Yan W; Liebow, Mark; Thompson, Carrie A; Ansell, Stephen M; Witzig, Thomas E; Tilly, Hervé; Haioun, Corinne; Molina, Thierry J; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans-Olov; Roos, Göran; Bracci, Paige M; Riby, Jacques; Smith, Martyn T; Holly, Elizabeth A; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M; Severson, Richard K; Tinker, Lesley F; North, Kari E; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J; Villano, Danylo J; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R; Turner, Jenny; Southey, Melissa C; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Boeing, Heiner; Tjønneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; De Vivo, Immaculata; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Liang, Liming; Park, Ju-Hyun; Chung, Charles C; Weisenburger, Dennis D; Fraumeni, Joseph F; Salles, Gilles; Glenn, Martha; Cannon-Albright, Lisa; Curtin, Karen; Wu, Xifeng; Smedby, Karin E; de Sanjose, Silvia; Skibola, Christine F; Berndt, Sonja I; Birmann, Brenda M; Chanock, Stephen J; Rothman, Nathaniel

    2016-01-01

    Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might mis

  6. Clinical Implications of Phosphorylated STAT3 Expression in de novo Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Ok, Chi Y; Chen, Jiayu; Xu-Monette, Ziju

    2014-01-01

    of phosphorylated STAT3 (pSTAT3) on prognosis are limited. EXPERIMENTAL DESIGN: We evaluated expression of pSTAT3 in de novo DLBCL using immunohistochemistry, gene expression profiling (GEP), and gene set enrichment analysis (GSEA). Results were analyzed in correlation with cell-of-origin (COO), critical lymphoma...

  7. Primary diffuse large B-cell lymphoma of the prostate in a young patient

    Directory of Open Access Journals (Sweden)

    Carlos A. Alvarez

    2006-02-01

    Full Text Available We report a primary lymphoma of the prostate, which arose in a 29-year-old man with hematuria. Pathological evaluation of tissue fragments allowed us to choose appropriate medical management. A diagnosis of suspicion can be performed by urine cytology, and molecular techniques may be helpful. Emphasis in differential diagnosis is made.

  8. Gene selection and cancer type classification of diffuse large-B-cell lymphoma using a bivariate mixture model for two-species data.

    Science.gov (United States)

    Su, Yuhua; Nielsen, Dahlia; Zhu, Lei; Richards, Kristy; Suter, Steven; Breen, Matthew; Motsinger-Reif, Alison; Osborne, Jason

    2013-01-05

    : A bivariate mixture model utilizing information across two species was proposed to solve the fundamental problem of identifying differentially expressed genes in microarray experiments. The model utility was illustrated using a dog and human lymphoma data set prepared by a group of scientists in the College of Veterinary Medicine at North Carolina State University. A small number of genes were identified as being differentially expressed in both species and the human genes in this cluster serve as a good predictor for classifying diffuse large-B-cell lymphoma (DLBCL) patients into two subgroups, the germinal center B-cell-like diffuse large B-cell lymphoma and the activated B-cell-like diffuse large B-cell lymphoma. The number of human genes that were observed to be significantly differentially expressed (21) from the two-species analysis was very small compared to the number of human genes (190) identified with only one-species analysis (human data). The genes may be clinically relevant/important, as this small set achieved low misclassification rates of DLBCL subtypes. Additionally, the two subgroups defined by this cluster of human genes had significantly different survival functions, indicating that the stratification based on gene-expression profiling using the proposed mixture model provided improved insight into the clinical differences between the two cancer subtypes.

  9. T-cell population of primary and secondary cutaneous B-cell lymphomas does not express the cutaneous lymphocyte-associated antigen (CLA).

    Science.gov (United States)

    Marti, R M; Hausmann, G; Estrach, T; Cid, M C; Palou, J; Herrero, C; Mascaro, J M

    1997-05-01

    Primary cutaneous B-cell lymphomas (CBCL) are a group of malignant lymphomas with apparently distinct clinicopathological and immunophenotypical features. As in other B-cell lymphomas, the accompanying benign cell population in CBCL includes a variable number of T lymphocytes whose role is not well understood. In the present study we characterized the immunophenotype of these T cells and compared it with that of the reactive T-cell population in specific skin involvement by noncutaneous B-cell malignancies. Our results indicated that most T cells in both primary and secondary B-cell lymphomas were CLA+ memory/effector helper T cells which differed from the currently known CLA+ memory/effector helper T lymphocytes of the skin-associated lymphoid tissue (SALT) system. However, the endothelial CLA ligand, E-selectin, was expressed on dermal vessels. These results suggest that a B cell environment and/or a lack of epidermal involvement promote(s) the recruitment into the skin of a different, apparently less specific, subset of memory helper T cells from those seen in T-cell-mediated dermatoses.

  10. TBL1XR1/TP63: a novel recurrent gene fusion in B-cell non-Hodgkin lymphoma | Office of Cancer Genomics

    Science.gov (United States)

    Recently, the landscape of single base mutations in diffuse large B-cell lymphoma (DLBCL) was described. Here we report the discovery of a gene fusion between TBL1XR1 and TP63, the only recurrent somatic novel gene fusion identified in our analysis of transcriptome data from 96 DLBCL cases. Based on this cohort and a further 157 DLBCL cases analyzed by FISH, the incidence in de novo germinal center B cell-like (GCB) DLBCL is 5% (6 of 115).

  11. Human Leukocyte Antigen Class I and II Alleles and Overall Survival in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma

    Directory of Open Access Journals (Sweden)

    Yani Lu

    2011-01-01

    Full Text Available Genetic variation in the 6p21 chromosomal region, including human leukocyte antigen (HLA genes and tumor necrosis factor (TNF, has been linked to both etiology and clinical outcomes of lymphomas. We estimated the effects of HLA class I (A, B, and C, class II DRB1 alleles, and the ancestral haplotype (AH 8.1 (HLAA*01-B*08-DRB1*03-TNF-308A on overall survival (OS among patients with diffuse large B-cell lymphoma (DLBCL and follicular lymphoma (FL in a population-based study of non-Hodgkin lymphoma. During a median followup of 89 months, 31% (52 of 166 DLBCL and 28% (46 of 165 FL patients died. Using multivariate Cox regression models, we observed statistically significant associations between genetic variants and survival: HLA-Cw*07:01 was associated with poorer OS among DLBCL patients (Hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.01–3.05; HLA-A*01:01 was associated with poorer OS (HR = 2.23, 95% CI = 1.24–4.01, and HLA-DRB1*13 (HR = 0.12, 95% CI = 0.02–0.90 and HLA-B Bw4 (HR = 0.36, 95% CI = 0.20–0.63 with better OS among FL patients. These results support a role for HLA in the prognosis of DLBCL and FL and represent a promising class of prognostic factors that warrants further evaluation.

  12. Occurrence of anaplastic large cell lymphoma following IgG4-related autoimmune pancreatitis and cholecystitis and diffuse large B-cell lymphoma.

    Science.gov (United States)

    Ishida, Mitsuaki; Hodohara, Keiko; Yoshida, Keiko; Kagotani, Akiko; Iwai, Muneo; Yoshii, Miyuki; Okuno, Hiroko; Horinouchi, Akiko; Nakanishi, Ryota; Harada, Ayumi; Yoshida, Takashi; Okabe, Hidetoshi

    2013-01-01

    IgG4-related sclerosing disease is an established disease entity with characteristic clinicopathological features. Recently, the association between IgG4-related sclerosing disease and the risk of malignancies has been suggested. IgG4-related autoimmune pancreatitis with pancreatic cancer has been reported. Further, a few cases of extraocular malignant lymphoma in patients with IgG4-related sclerosing disease have also been documented. Herein, we describe the first documented case of anaplastic large cell lymphoma (ALCL) following IgG4-related autoimmune pancreatitis and cholecystitis and diffuse large B-cell lymphoma (DLBCL). A 61-year-old Japanese male, with a past history of DLBCL, was detected with swelling of the pancreas and tumorous lesions in the gallbladder. Histopathological study of the resected gallbladder specimen revealed diffuse lymphoplasmacytic infiltration with fibrosclerosis in the entire gallbladder wall. Eosinophilic infiltration and obliterative phlebitis were also noted. Immunohistochemically, many IgG4-positive plasma cells had infiltrated into the lesion, and the ratio of IgG4/IgG-positive plasma cells was 71.6%. Accordingly, a diagnosis of IgG4-related cholecystitis was made. Seven months later, he presented with a painful tumor in his left parotid gland. Histopathological study demonstrated diffuse or cohesive sheet-like proliferation of large-sized lymphoid cells with rich slightly eosinophilic cytoplasm and irregular-shaped large nuclei. These lymphoid cells were positive for CD30, CD4, and cytotoxic markers, but negative for CD3 and ALK. Therefore, a diagnosis of ALK-negative ALCL was made. It has been suggested that the incidence of malignant lymphoma may be high in patients with IgG4-related sclerosing disease, therefore, intense medical follow-up is important in patients with this disorder.

  13. Genomic profiling of plasmablastic lymphoma using array comparative genomic hybridization (aCGH: revealing significant overlapping genomic lesions with diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Lu Xin-Yan

    2009-11-01

    Full Text Available Abstract Background Plasmablastic lymphoma (PL is a subtype of diffuse large B-cell lymphoma (DLBCL. Studies have suggested that tumors with PL morphology represent a group of neoplasms with clinopathologic characteristics corresponding to different entities including extramedullary plasmablastic tumors associated with plasma cell myeloma (PCM. The goal of the current study was to evaluate the genetic similarities and differences among PL, DLBCL (AIDS-related and non AIDS-related and PCM using array-based comparative genomic hybridization. Results Examination of genomic data in PL revealed that the most frequent segmental gain (> 40% include: 1p36.11-1p36.33, 1p34.1-1p36.13, 1q21.1-1q23.1, 7q11.2-7q11.23, 11q12-11q13.2 and 22q12.2-22q13.3. This correlated with segmental gains occurring in high frequency in DLBCL (AIDS-related and non AIDS-related cases. There were some segmental gains and some segmental loss that occurred in PL but not in the other types of lymphoma suggesting that these foci may contain genes responsible for the differentiation of this lymphoma. Additionally, some segmental gains and some segmental loss occurred only in PL and AIDS associated DLBCL suggesting that these foci may be associated with HIV infection. Furthermore, some segmental gains and some segmental loss occurred only in PL and PCM suggesting that these lesions may be related to plasmacytic differentiation. Conclusion To the best of our knowledge, the current study represents the first genomic exploration of PL. The genomic aberration pattern of PL appears to be more similar to that of DLBCL (AIDS-related or non AIDS-related than to PCM. Our findings suggest that PL may remain best classified as a subtype of DLBCL at least at the genome level.

  14. Sleeping Beauty transposon screen identifies signaling modules that cooperate with STAT5 activation to induce B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Heltemes-Harris, L M; Larson, J D; Starr, T K; Hubbard, G K; Sarver, A L; Largaespada, D A; Farrar, M A

    2016-06-30

    Signal transducer and activator of transcription 5 (STAT5) activation occurs frequently in human progenitor B-cell acute lymphoblastic leukemia (B-ALL). To identify gene alterations that cooperate with STAT5 activation to initiate leukemia, we crossed mice expressing a constitutively active form of STAT5 (Stat5b-CA) with mice in which a mutagenic Sleeping Beauty transposon (T2/Onc) was mobilized only in B cells. Stat5b-CA mice typically do not develop B-ALL (<2% penetrance); in contrast, 89% of Stat5b-CA mice in which the T2/Onc transposon had been mobilized died of B-ALL by 3 months of age. High-throughput sequencing approaches were used to identify genes frequently targeted by the T2/Onc transposon; these included Sos1 (74%), Kdm2a (35%), Jak1 (26%), Bmi1 (19%), Prdm14 or Ncoa2 (13%), Cdkn2a (10%), Ikzf1 (8%), Caap1 (6%) and Klf3 (6%). Collectively, these mutations target three major cellular processes: (i) the Janus kinase/STAT5 pathway (ii) progenitor B-cell differentiation and (iii) the CDKN2A tumor-suppressor pathway. Transposon insertions typically resulted in altered expression of these genes, as well as downstream pathways including STAT5, extracellular signal-regulated kinase (Erk) and p38. Importantly, expression of Sos1 and Kdm2a, and activation of p38, correlated with survival, further underscoring the role these genes and associated pathways have in B-ALL.

  15. Rituximab in Combination with CHOP, an Effective and Well-tolerated Salvage Regimen for Diffuse Large B-Cell Lymphoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To evaluate the clinical effect of the R-CHOP regimen (rituximab in combination with cyclophosphamide, epirubicin, vincristine and prednisone) in treating refractory or relapsed diffuse large B-cell lymphoma (DLBCL), as a salvage therapy for DLBCL.METHODS Eighteen patients with refractory or relapsed DLBCL who were treated with the R-CHOP regimen from 2001 to 2006 in hospitals in Jilin Province were analyzed retrospectively. The response rate, change of serum lactate dehydrogenase (LDH), time to progression (TTP) and toxicity were observed.RESULTS The R-CHOP regimen can achieve a higher response rate, decrease serum LDH to a larger extent and obtain longer TTP than a conventional secondary regimen. The main adverse effects were similar to conventional chemotherapy.CONCLUSION The R-CHOP regimen is one of the most effective secondary therapies for DLBCL.

  16. Expression of a truncated Hmga1b gene induces gigantism, lipomatosis and B-cell lymphomas in mice.

    Science.gov (United States)

    Fedele, Monica; Visone, Rosa; De Martino, Ivana; Palmieri, Dario; Valentino, Teresa; Esposito, Francesco; Klein-Szanto, Andres; Arra, Claudio; Ciarmiello, Andrea; Croce, Carlo M; Fusco, Alfredo

    2011-02-01

    HMGA1 gene rearrangements have been frequently described in human lipomas. In vitro studies suggest that HMGA1 proteins have a negative role in the control of adipocyte cell growth, and that HMGA1 gene truncation acts in a dominant-negative fashion. Therefore, to define better the role of the HMGA1 alterations in the generation of human lipomas, we generated mice carrying an Hmga1b truncated (Hmga1b/T) gene. These mice develop a giant phenotype together with a drastic expansion of the retroperitoneal and subcutaneous white adipose tissue. We show that the activation of the E2F pathway likely accounts, at least in part, for this phenotype. Interestingly, the Hmga1b/T mice also develop B-cell lymphomas similar to that occurring in Hmga1-knockout mice, supporting a dominant-negative role of the Hmga1b/T mutant also in vivo.

  17. Investigation of MGMT and DAPK1 methylation patterns in diffuse large B-cell lymphoma using allelic MSP-pyrosequencing

    DEFF Research Database (Denmark)

    Kristensen, Lasse Sommer; Treppendahl, Marianne Bach; Asmar, Fazila;

    2013-01-01

    The tumor suppressor genes MGMT and DAPK1 become methylated in several cancers including diffuse large B-cell lymphoma (DLBCL). However, allelic methylation patterns have not been investigated in DLBCL. We developed a fast and cost-efficient method for the analysis of allelic methylation based...... on pyrosequencing of methylation specific PCR (MSP) products including a SNP. Allelic methylation patterns were reliably analyzed in standards of known allelic methylation status even when diluted in unmethylated DNA to below 1% methylation. When studying 148 DLBCL patients MGMT and DAPK1 methylation was observed...... in 19% and 89%, respectively, and among methylated and heterozygous patients 29% and 55%, respectively, were biallelically methylated. An association between the T-allele of the rs16906252 SNP and MGMT methylation was observed (p-value=0.04), and DAPK1 methylation of the A-allele was associated...

  18. Frequent disruption of the RB1 pathway in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Kania, P W; Ino, Y

    2000-01-01

    downstream of exon 3 generating a novel splice signal. Seven tumours (21%) showed cyclin D3 overexpression, including all three thyroid lymphomas (P = 0.006). Cyclin D3 overexpression and p16INK4A/pRb aberrations were mutually exclusive, supporting an oncogenic role for cyclin D3 in DLCL. p16INK4A...... expression was associated with treatment failure (P = 0.020), and multivariate analysis of overall survival identified both low E2F-1 expression (relative risk = 6.9; P = 0.0037) and p16INK4A inactivation (relative risk = 3.3; P = 0.0247) as independent prognostic markers. These data support a role of E2F-1...... as tumour suppressor gene in lymphoma and strongly suggest that the RB1 and p53 pathways are important in the development of de novo DLCL. Furthermore, low E2F-1 expression and p16INK4A inactivation may serve as prognostic markers for patients with this type of lymphoma....

  19. Elevation of serum interleukins 8, 4, and 1β levels in patients with gastrointestinal low-grade B-cell lymphoma.

    Science.gov (United States)

    Miyata-Takata, Tomoko; Takata, Katsuyoshi; Toji, Tomohiro; Goto, Naoe; Kasahara, Senji; Takahashi, Takeshi; Tari, Akira; Noujima-Harada, Mai; Miyata, Takafumi; Sato, Yasuharu; Yoshino, Tadashi

    2015-12-17

    Proinflammatory cytokines that are produced by helper T cells (Th) regulate immune reactions, facilitate class switching of B cells, and prolong the lifespan of B and T cells. Eradication therapy using antibiotics is sometimes effective against gastrointestinal (GI) malignant lymphoma, suggesting that the tumor development or progression is affected by the inflammatory microenvironment. In the present study, serum samples from 148 patients with various subtypes of malignant lymphoma were tested for 11 proinflammatory Th1/Th2 cytokines. In the comparison by subtype or GI lesions, serum interleukin (IL)-8 (P = 6.7E-05), IL-4 (P = 7.5E-05), and IL-1β (P = 0.0043) levels showed significant differences among subtypes, being particularly elevated in follicular lymphomas (FL) and mucosa-associated lymphoid tissue (MALT) lymphomas. Serum IL-8 levels were elevated in GI-FL and MALT lymphomas, and serum IL-4 and IL-1 β levels were elevated in MALT lymphomas. These findings show that GI low-grade B-cell lymphoma could develop against the background of an inflammatory microenvironment. Thus, these cytokines may be useful as diagnostic markers and could provide new insights into tumor development.

  20. Primary B-Cell Mucosa-Associated Lymphoid Tissue Lymphoma of the Hard Palate and Parotid Gland: Report of One Case and Review of the Literature

    Science.gov (United States)

    Yonal-Hindilerden, Ipek; Hindilerden, Fehmi; Arslan, Serkan; Turan-Guzel, Nalan; Dogan, Ibrahim Oner; Nalcaci, Meliha

    2016-01-01

    A 61-year-old woman was admitted to our hospital with an ulcerated palate mass and swelling of the right parotid gland. Incisional biopsy from the hard palate revealed an extranodal marginal zone B-cell lymphoma, also called mucosa-associated lymphoid tissue (MALT) lymphoma. Final diagnosis was MALT lymphoma of the parotid gland with concomitant involvement of an extremely seldom site of involvement: the hard palate. To our knowledge, this report illustrates the first case of MALT lymphoma of the hard palate and parotid gland without an underlying autoimmune disease. Rituximab-based combination regimen (R-CHOP) provided complete remission with total regression of mass lesions at the hard palate and parotid gland. At 44-month follow-up, there is no disease relapse. We adressed the manifestations and management of MALT lymphoma patients with involvement of salivary gland and oral cavity. PMID:27738485

  1. Diphtheria Toxin/Human B-Cell Activating Factor Fusion Protein Kills Human Acute Lymphoblastic Leukemia BALL-1 Cells: An Experimental Study

    Institute of Scientific and Technical Information of China (English)

    Xin-pu Gao; Zheng-min Liu; Yu-lian Jiao; Bin Cui; Yue-ting Zhu; Jie Zhang; Lai-cheng Wang; Yue-ran Zhao

    2012-01-01

    Objective:This study aimed to express a fusion protein of diphtheria toxin and human B ceil-activating factor (DT388sBAFF) in Escherichia coli (E.coli) and investigate its activity in human B-lineage acute lymphoblastic leukemia 1 cells (BALL-1).Methods:A fragment of DT388sBAFF fusion gene was separated from plasmid pUC57-DT388sBAFF digested with Nde Ⅰ and Xho Ⅰ,and inserted into the expression vector pcold Ⅱ digested with the same enzymes.Recombinants were screened by the colony polymerase chain reaction (PCR) and restriction map.The recombinant expression vector was transformed into BL21 and its expression was induced by isopropyl β-D-1-thiogalactopyranoside (IPTG).The recombinant protein was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot,and then purified by Ni2+-NTA affinity chromatography.The expression level of B cell-activating factor receptor (BAFF-R) on BALL-1 cells was assessed by real-time PCR.The receptor binding capacity of recombinant protein was determined by cell fluorescent assay.The specific cytotoxicity of recombinant protein on BALL-1 cells was detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay.Results:The expression level of recombinant protein was 50% of total bacterial proteins in E.coli,and the recombinant protein could bind to BAFF-R-positive BALL-1 cells and thereby produce a cytotoxic effect on the cells.Conclusion:The fusion protein expression vector DT388sBAFF was successfully constructed and the recombinant protein with selective cytotoxicity against BALL-1 cells was obtained,providing foundation for further study of the therapy of human B-lineage acute lymphoblastic leukemia.

  2. Long-term complete remission in a patient with intravascular large B-cell lymphoma with central nervous system involvement

    Directory of Open Access Journals (Sweden)

    Sawada T

    2014-11-01

    Full Text Available Takeshi Sawada,1 Yasushi Omuro,1 Takeshi Kobayashi,2 Tunekazu Hishima,3 Fumiaki Koizumi,4 Yusuke Kanemasa,1 Tatsu Shimoyama,1 Eisaku Sasaki,1 Yoshiharu Maeda1 1Department of Chemotherapy, 2Department of Hematology, 3Department of Pathology, 4Department of Laboratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo, Japan Abstract: This report describes a patient with intravascular large B-cell lymphoma (IVLBCL with central nervous system involvement at the time of diagnosis who achieved complete remission for over 5 years in response to therapy. The patient, a 71 year-old woman, was previously healthy with the exception of taking verapamil for paroxysmal supraventricular tachycardia. She had presented with pyrexia and gradually progressive anemia. Brain magnetic resonance imaging revealed an infarct-like lesion in the pons, although no paralysis was observed. She was diagnosed with IVLBCL on the basis of random skin biopsy. After eight cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, abnormal laboratory data had normalized, and no pontine lesion was evident on magnetic resonance imaging without receiving any intrathecal chemotherapy. IVLBCL is associated with poor prognosis, particularly in patients with central nervous system involvement. Early initiation of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy and drug interactions between anticancer agents and verapamil as a p-glycoprotein inhibitor were considered the possible reasons for favorable outcome in the present case. Keywords: intravascular large B-cell lymphoma, random skin biopsy, CNS involvement, rituximab, verapamil, blood–brain barrier

  3. Diffuse Large B-Cell Lymphoma Transformed from Mucosa-Associated Lymphoid Tissue Lymphoma Arising in a Female Urethra Treated with Rituximab for the First Time

    Directory of Open Access Journals (Sweden)

    A. Al Zahrani

    2012-05-01

    Full Text Available A 30-year-old female patient presented to the gynecology clinic with a small (painless swelling at the urethral orifice. She underwent surgical excision of the lesion. Pathological examination revealed non-Hodgkin’s lymphoma of diffuse large B-cell type and mucosa-associated lymphoid tissue type, stage IE. The patient refused radiotherapy. Accordingly, we started CHOP-R chemotherapy. She received a total of 6 cycles of CHOP and 8 cycles of rituximab. Patient follow-up was done 3 months later through CT scan and cytoscopy confirming the complete remission. The patient has been disease-free for 4 years. We reviewed 26 cases of this rare entity reported previously.

  4. Antemortem diagnosis with multiple random skin biopsies and transbronchial lung biopsy in a patient with intravascular large B-cell lymphoma, the so-called Asian variant lymphoma.

    Science.gov (United States)

    Nishizawa, Tomotaka; Saraya, Takeshi; Ishii, Haruyuki; Goto, Hajime

    2014-03-14

    A 59-year-old, previously healthy man presented to our hospital, with a 3-month history of high fever, nocturnal sweating and exertional dyspnoea. Aggressive diagnostic procedures such as multiple random skin biopsies and transbronchial lung biopsy (TBLB) led to an antemortem diagnosis of intravascular large B-cell lymphoma (IVLBCL), which showed abundant CD20 atypical lymphocytes aggregated in lumina of small vessels. The 29 cases diagnosed with IVLBCL during their lifetime by TBLB were reviewed. Their clinical features included respiratory symptoms (hypoxaemia, dyspnoea and dry cough) and persistent fever. IVLBCL patients show various radiological patterns (ground glass opacities, multiple centrilobular nodules, interlobular septal thickening, interstitial shadows and thickening of bronchovascular bundles), suggesting lymphatic or haematological spread. Antemortem diagnosis of IVLBCL is difficult, but a multidisciplinary approach, with aggressive multiple random skin biopsies and/or TBLB, should be considered in patients with respiratory symptoms that are refractory to antibiotics or prednisolone treatment.

  5. Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma

    Directory of Open Access Journals (Sweden)

    Kai Qing

    2016-08-01

    Full Text Available Abstract We demonstrate the synergistic antitumor effect of oridonin and the PI3K/mTOR inhibitor NVP-BEZ235 on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma (non-GCB DLBCL both in vitro and in vivo. The underlying mechanism may be multifunctional, involving apoptosis, AKT/mTOR and NF-kB inactivation, and ROS-mediated DNA damage response. Our findings pave the way for a new potential treatment option for non-GCB DLBCL with the combination of oridonin and NVP-BEZ235.

  6. Risk factors and patterns of lymph node involvement in primary gastric large B-cell lymphoma: implications for target definition

    Directory of Open Access Journals (Sweden)

    Zhang X

    2016-07-01

    Full Text Available Ximei Zhang, Peiguo Wang, Lujun Zhao, Zhiyong Yuan, Ping Wang Department of Radiation Oncology, Tianjin’s Clinical Research Center for Cancer and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, People’s Republic of China Background: The aim of this study was to identify the appropriate radiation volume for primary gastric diffuse large B-cell lymphoma (PG-DLBCL.Methods: We retrospectively analyzed the clinical and pathological findings of 68 patients treated with total gastrectomy and D2 lymphadenectomy.Results: There were 23, 14, and 29 patients with stage I, stage II, and stage IIE disease, respectively, and 30 patients had lymph node involvement. Primary tumor location, as well as the depth of invasion, was significantly associated with lymph node involvement. When the tumor was limited to the muscularis, the involved lymph nodes were found to be perigastric nodes. For tumors invading beyond the muscularis, regional lymph nodes were involved.Conclusion: The optimal radiation volume for patients with PG-DLBCL is largely dependent on the primary location and depth of invasion. Larger series and longer follow-up are needed to further delineate the radiation volumes for PG-DLBCL. Keywords: primary gastric lymphoma, failure patterns, radiotherapy, chemotherapy, prognosis

  7. Spontaneous Remission of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma of the Elderly

    Directory of Open Access Journals (Sweden)

    T. Mizuno

    2013-05-01

    Full Text Available A 94-year-old female patient presented with anorexia and left axillar lymphadenopathy on admission. Her past history was angina pectoris at 83 years of age and total gastrectomy due to gastric cancer at 87 years. The family history revealed that her son had had a malignant lymphoma, the histopathological diagnosis of which was diffuse large B-cell lymphoma. A physical examination showed both cervical, axillar, and inguinal lymphadenopathy without tenderness. She had elevated lactate dehydrogenase, ferritin, and soluble interleukin-2 receptor (sIL-2R. Whole-body computed tomography confirmed the cervical, axillary, and inguinal lymphadenopathy. Gallium-68 imaging revealed positive accumulation in these superficial lymph nodes. A right inguinal lymph node biopsy showed features of Epstein-Barr virus-associated lymphoproliferative disorder. Immunohistological studies on this lymph node biopsy showed CD20-positive large cells, CD3-positive small cells, and CD30-partly-positive large cells. In situ hybridization showed Epstein-Barr virus-positive, LMP-partly-positive, and EBNA2-negative cells. She refused chemotherapy as her son had died from hematemesis during chemotherapy. She received intravenous hyperalimentation for 1 month after admission. No palpable lymph nodes were identified by physical examination or computed tomography 3 months after admission, and regression of lactate dehydrogenase, ferritin, and sIL-2R was observed. She recovered from anorexia and was discharged. She died from pneumonia 10 months later after initial symptoms of anorexia. The autopsy showed no superficial lymphadenopathy.

  8. [MGMT expression in primary central nervous system diffuse large B cell lymphoma and its relationship with prognosis].

    Science.gov (United States)

    Shi, Q Y; Feng, X; Wang, J J; Wang, X; Bao, W; Ma, J; Shi, Q L

    2016-12-08

    Objective: To study the correlation between MGMT expression, clinicopathologic features and post-chemotherapy prognosis in patients with primary central nervous system lymphoma diffuse large B-cell lymphoma (PCNS-DLBCL). Methods: MGMT expression was detected in 76 cases of PCNS-DLBCL by EnVision method with immunohistochemical staining.Follow-up data including treatment response and overall survival time, were analyzed. Results: The rate of MGMT expression in PCNS-DLBCL was 67.1%(51/76). The MGMT expression rate in male patients was higher than that in female(PMGMT and aged over 60 years was shorter after chemotherapy than those without chemotherapy (P=0.022). In the patients aged over 60 years, the prognosis of MGMT-positive patients was significantly better than MGMT-negative patients (P=0.044). Conclusions: The expression of MGMT is more commonly found in male patients. In the patients aged over 60 years with the same therapy, the prognosis is better in the MGMT-negative ones. Detection of MGMT protein expression can provide some guidance in choice of treatment modalities in PCNS-DLBCL patients.

  9. Extranodal diffuse large B-cell lymphoma: Experience from a tertiary care oncology center in South India

    Directory of Open Access Journals (Sweden)

    K. C. Lakshmaiah

    2014-01-01

    Full Text Available Aims: Diffuse large B-cell lymphoma (DLBCL is the most common non-Hodgkin′s lymphoma (NHL with frequent extra nodal (EN presentation. The overall occurrence of lymphomas has been increasing; however, those of EN-NHL have been increasing much more rapidly. There is limited data found on EN-DLBCL in the Indian population and hence we carried out this retrospective observational study of primary EN-DLBCL at our center in Southern India. Materials and Methods: A total of 90 consecutive cases diagnosed as EN-DLBCL (according to the standard criteria by tissue biopsy confirmed by immunohistochemistry between 2007 and 2011 were included. Staging workup including computed tomography of neck, thorax and abdomen and pelvis, bone marrow aspiration and biopsy was done and International Prognostic Index (IPI calculated. Staging was according to Cotswold′s modification of Ann Arbor. The actuarial survival analysis was performed by Kaplan-Meier. Data were analyzed using the SPSS (version 16 statistical software. Results: The median age in this study was 49 years (18-88 with results showing EN-DLBCL to be 1.36 times more common in males. Advanced stages were seen in 15 subjects (16.6% and bulky disease in 13 subjects (14.4%. CD20 was positive in 89 (98.8% while 32 had high serum lactate dehydrogenase. According to the IPI most were low-risk-56 (66.6%. Overall response rate for the various combination chemotherapies was 85.7% with complete response in 62.3%. The overall survival range spanned from 2 to 123 months. Univariate analysis showed only bulky disease was associated with inferior survival. Conclusions: EN-DLBCL was present at an early age compared to nodal DLBCL, present more often in early stage and low IPI score. Chemoimmunotherapy with radiotherapy to the EN or bulky site is the standard treatment at present.

  10. Panobinostat acts synergistically with ibrutinib in diffuse large B cell lymphoma cells with MyD88 L265 mutations

    Science.gov (United States)

    Mondello, Patrizia; Brea, Elliott J.; De Stanchina, Elisa; Toska, Eneda; Chang, Aaron Y.; Fennell, Myles; Seshan, Venkatraman; Garippa, Ralph; Scheinberg, David A.; Baselga, José; Wendel, Hans-Guido

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) frequently harbors genetic alterations that activate the B cell receptor (BCR) and TLR pathways, which converge to activate NF-κB. While selective inhibition of BTK with ibrutinib causes clinical responses in relapsed DLBCL patients, most responses are partial and of a short duration. Here, we demonstrated that MyD88 silencing enhanced ibrutinib efficacy in DLBCL cells harboring MyD88 L265P mutations. Chemical downregulation of MyD88 expression with HDAC inhibitors also synergized with ibrutinib. We demonstrate that HDAC inhibitor regulation of MyD88 expression is mediated by STAT3. In turn, STAT3 silencing caused a decrease in MyD88 mRNA and protein levels, and enhanced the ibrutinib antilymphoma effect in MyD88 mutant DLBCL cells. Induced mutations in the STAT3 binding site in the MyD88 promotor region was associated with a decrease in MyD88 transcriptional activity. We also demonstrate that treatment with the HDAC inhibitor panobinostat decreased phosphorylated STAT3 binding to the MyD88 promotor. Accordingly, combined treatment with panobinostat and ibrutinib resulted in enhanced inhibition of NF-κB activity and caused regression of DLBCL xenografts. Our data provide a mechanistic rationale for combining HDAC inhibitors and ibrutinib for the treatment of DLBCL. PMID:28352655

  11. Protein kinase C inhibitor sotrastaurin selectively inhibits the growth of CD79 mutant diffuse large B-cell lymphomas.

    Science.gov (United States)

    Naylor, Tara L; Tang, Huaping; Ratsch, Boris A; Enns, Andreas; Loo, Alice; Chen, Liqing; Lenz, Peter; Waters, Nigel J; Schuler, Walter; Dörken, Bernd; Yao, Yung-Mae; Warmuth, Markus; Lenz, Georg; Stegmeier, Frank

    2011-04-01

    The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) correlates with poor prognosis. The ABC subtype of DLBCL is associated with constitutive activation of the NF-κB pathway, and oncogenic lesions have been identified in its regulators, including CARD11/CARMA1 (caspase recruitment domain-containing protein 11), A20/TNFAIP3, and CD79A/B. In this study, we offer evidence of therapeutic potential for the selective PKC (protein kinase C) inhibitor sotrastaurin (STN) in preclinical models of DLBCL. A significant fraction of ABC DLBCL cell lines exhibited strong sensitivity to STN, and we found that the molecular nature of NF-κB pathway lesions predicted responsiveness. CD79A/B mutations correlated with STN sensitivity, whereas CARD11 mutations rendered ABC DLBCL cell lines insensitive. Growth inhibitory effects of PKC inhibition correlated with NF-κB pathway inhibition and were mediated by induction of G₁-phase cell-cycle arrest and/or cell death. We found that STN produced significant antitumor effects in a mouse xenograft model of CD79A/B-mutated DLBCL. Collectively, our findings offer a strong rationale for the clinical evaluation of STN in ABC DLBCL patients who harbor CD79 mutations also illustrating the necessity to stratify DLBCL patients according to their genetic abnormalities.

  12. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography after one cycle of chemotherapy in patients with diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Mylam, Karen Juul; Kostakoglu, Lale; Hutchings, Martin;

    2015-01-01

    We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) s...

  13. Single nucleotide variation in the TP53 3' untranslated region in diffuse large B-cell lymphoma treated with rituximab-CHOP

    DEFF Research Database (Denmark)

    Li, Yong; Gordon, Michael W; Xu-Monette, Zijun Y;

    2013-01-01

    We identified multiple single nucleotide variants (SNVs) in the TP53 3' untranslated region (3'UTR) in tumor specimens from 244 patients with diffuse large B-cell lymphoma (DLBCL). Patients carrying a wild-type TP53 coding sequence (CDS) and 1 or more 3'UTR SNVs had a better 5-year survival rate ...

  14. Reciprocal expression of the endocytic protein HIP1R and its repressor FOXP1 predicts outcome in R-CHOP-treated diffuse large B-cell lymphoma patients

    DEFF Research Database (Denmark)

    Wong, K K; Gascoyne, D M; Brown, P J

    2014-01-01

    We previously identified autoantibodies to the endocytic-associated protein Huntingtin-interacting protein 1-related (HIP1R) in diffuse large B-cell lymphoma (DLBCL) patients. HIP1R regulates internalization of cell surface receptors via endocytosis, a process relevant to many therapeutic strateg...

  15. Combination of rituximab with autologous peripheral blood stem cell transplantation for treatment of diffuse large B-cell lymphoma:a single-center experience

    Institute of Scientific and Technical Information of China (English)

    梁赜隐

    2013-01-01

    Objective To investigate whether incorporation of rituximab into high-dose chemotherapy with autologous peripheral blood stem cell transplantation(auto-PBSCT) could improve the survival of patients with diffuse large B-cell lymphoma(DLBCL),and evaluate the safety of

  16. The value of routine bone marrow biopsy in patients with diffuse large B-cell lymphoma staged with PET/CT

    DEFF Research Database (Denmark)

    Alzahrani, M; El-Galaly, T C; Hutchings, M

    2016-01-01

    BACKGROUND: The added diagnostic and prognostic value of routine bone marrow biopsy (BMB) in patients with diffuse large B-cell lymphoma (DLBCL) undergoing positron emission tomography combined with computed tomography (PET/CT) staging is controversial. PATIENTS AND METHODS: Patients with newly d...

  17. FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures

    DEFF Research Database (Denmark)

    Wong, Kah Keng; Gascoyne, Duncan M; Soilleux, Elizabeth J;

    2016-01-01

    FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor p...

  18. MYC translocation partner gene determines survival of patients with large B-cell lymphoma with MYC- or double-hit MYC/BCL2 translocations

    DEFF Research Database (Denmark)

    Pedersen, Mette Ø; Gang, Anne O; Poulsen, Tim S;

    2014-01-01

    In large B-cell lymphoma (LBCL) MYC- and MYC/BCL2 double-hit (DH) translocations have been associated with inferior survival. We hypothesised that the negative prognostic impact of MYC translocation was determined by an immunoglobulin MYC translocation partner gene (IG-MYC), as opposed to a non-i...

  19. Cell of origin predicts outcome to treatment with etoposide-containing chemotherapy in young patients with high-risk diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Gang, Anne O; Pedersen, Mette Ø; Knudsen, Helle;

    2015-01-01

    Addition of etoposide to the R-CHOP chemotherapy regimen with cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab (R-CHOEP) has resulted in improved survival in young patients with high-risk diffuse large B-cell lymphoma (DLBCL). It is not known whether biological factors can...

  20. Differential Expression of miR-155 and miR-21 in Tumor and Stroma Cells in Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    Munch-Petersen, Helga D; Ralfkiaer, Ulrik; Sjö, Lene D;

    2015-01-01

    OncomiRs miR-21 and miR-155 have been linked to lymphomagenesis, but information on their implication in diffuse large B-cell lymphoma (DLBCL) is limited. Here, we used locked nucleic acid-based in situ hybridization (ISH) detection techniques on formalin-fixed paraffin-embedded DLBCL tissue...

  1. Matched unrelated donor allogeneic transplantation provides comparable long-term outcome to HLA-identical sibling transplantation in relapsed diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Avivi, I.; Canals, C.; Vernant, J.P.; Wulf, G.; Nagler, A.; Hermine, O.; Petersen, E.; Yakoub-Agha, I.; Craddock, C.; Schattenberg, A.V.; Niederwieser, D.; Thomson, K.; Blaise, D.; Attal, M.; Pfreundschuh, M.; Passweg, J.; Russell, N.; Dreger, P.; Sureda, A.

    2014-01-01

    The objective of this retrospective analysis was to compare outcomes of patients with diffuse large B-cell lymphoma (DLBCL) who received either a matched sibling (sib) or an unrelated donor (URD) allogeneic hematopoietic cell transplantation (allo-HCT). Long-term outcome of 172 DLBCL patients receiv

  2. Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Frei, E; Visco, C; Xu-Monette, Z Y;

    2013-01-01

    High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the 'rituximab...

  3. Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Frei, E.; Visco, C.; Xu-Monette, Z.Y.; Dirnhofer, S.; Dybkaer, K.; Orazi, A.; Bhagat, G.; Hsi, E.D.; Krieken, J.H.J.M. van; Ponzoni, M.; Go, R.S.; Piris, M.A.; Moller, M.B.; Young, K.H.; Tzankov, A.

    2013-01-01

    BACKGROUND: High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the '

  4. Correlations between functional imaging markers derived from PET/CT and diffusion-weighted MRI in diffuse large B-cell lymphoma and follicular lymphoma.

    Directory of Open Access Journals (Sweden)

    Xingchen Wu

    Full Text Available OBJECTIVES: To investigate the correlations between functional imaging markers derived from positron emission tomography/computed tomography (PET/CT and diffusion-weighted magnetic resonance imaging (DWI in diffuse large B-cell lymphoma (DLBCL and follicular lymphoma (FL. Further to compare the usefulness of these tumor markers in differentiating diagnosis of the two common types of Non-Hodgkin's lymphoma (NHL. MATERIALS AND METHODS: Thirty-four consecutive pre-therapy adult patients with proven NHL (23 DLBCL and 11 FL underwent PET/CT and MRI examinations and laboratory tests. The maximum standardized uptake value (SUV(max, metabolic tumor volume (MTV, and metabolic tumor burden (MTB were determined from the PET/CT images. DWI was performed in addition to conventional MRI sequences using two b values (0 and 800 s/mm(2. The minimum and mean apparent diffusion coefficient (ADC(min and ADC(mean were measured on the parametric ADC maps. RESULTS: The SUV(max correlated inversely with the ADC(min (r =  -0.35, p<0.05. The ADC(min, ADC(mean, serum thymidine kinase (TK, Beta 2-microglobulin (B2m, lactate dehydrogenase (LD, and C-reactive protein (CRP correlated with both whole-body MTV and whole-body MTB (p<0.05 or 0.01. The SUV(max, TK, LD, and CRP were significantly higher in the DLBCL group than in the FL group. Receiver operating characteristic curve analysis showed that they were reasonable predictors in differentiating DLBCL from FL. CONCLUSIONS: The functional imaging markers determined from PET/CT and DWI are associated, and the SUV(max is superior to the ADC(min in differentiating DLBCL from FL. All the measured serum markers are associated with functional imaging markers. Serum LD, TK, and CRP are useful in differentiating DLBCL from FL.

  5. Clinical outcomes and prognostic factors in patients with breast diffuse large B cell lymphoma; Consortium for Improving Survival of Lymphoma (CISL study

    Directory of Open Access Journals (Sweden)

    Lee Je-Jung

    2010-06-01

    Full Text Available Abstract Background The breast is a rare extranodal site of non-Hodgkin lymphoma, and primary breast lymphoma (PBL has been arbitrarily defined as disease localized to one or both breasts with or without regional lymph nodes involvement. The aim of this study was to evaluate the clinical outcomes in patients with diffuse large B cell lymphoma (DLBCL and breast involvement, and to find the criteria of PBL reflecting the outcome and prognosis. Methods We retrospectively analyzed data from 68 patients, newly diagnosed with DLBCL and breast involvement at 16 Korean institutions between January 1994 and June 2009. Results Median age at diagnosis was 48 years (range, 20-83 years. Forty-three (63.2% patients were PBL according to previous arbitrary criteria, sixteen (23.5% patients were high-intermediate to high risk of international prognostic index. The patients with one extranodal disease in the breast (OED with or without nodal disease were 49 (72.1%, and those with multiple extranodal disease (MED were 19 (27.9%. During median follow-up of 41.5 months (range, 2.4-186.0 months, estimated 5-year progression-free survival (PFS was 53.7 ± 7.6%, and overall survival (OS was 60.3 ± 7.2%. The 5-year PFS and OS was significantly higher for patients with the OED group than those with the MED group (5-year PFS, 64.9 ± 8.9% vs. 27.5 ± 11.4%, p = 0.001; 5-year OS, 74.3 ± 7.6% vs. 24.5 ± 13.0%, p Conclusions Our results show that the patients included in OED group, reflecting different treatment outcome, prognosis and pattern of progression, should be considered as PBL in the future trial. Further studies are warranted to validate our suggested criteria.

  6. RNA-binding protein VICKZ is expressed in a germinal center associated pattern among lymphoma subtypes

    DEFF Research Database (Denmark)

    Natkunam, Y.; Vainer, G.; Zhao, S.C.;

    2005-01-01

    to the cytoplasm. Among 868 non-Hodgkin and Hodgkin lymphomas tested by immunohistochemistry on tissue microarrays, staining for VICKZ protein was present in 76% (126/165) of follicular lymphoma, 78% (155/200) of DLBCL, 90% (9/10) of mediastinal large B-cell lymphoma, and 100% (2/2) of Burkitt lymphoma. A subset...... of mantle cell lymphoma (11%, 2/19), extranodal (8%, 2/25), and nodal (20%, 1/5) marginal zone lymphoma and lymphoblastic lymphoma (25%, 4/13), showed VICKZ staining. The majority of lymphocyte predominant Hodgkin (92%, 12/13) and classical Hodgkin (94%, 101/108) lymphoma were found to be positive. Among T......Recent effort in the molecular characterization of diffuse large B-cell lymphoma (DLBCL) has led to the recognition that patients with DLBCL of germinal center origin exhibit a better overall survival. Thus, identification and characterization of markers of germinal center derivation...

  7. Detection of dicentric chromosome (9;20) in paediatric B-cell acute lymphoblastic leukaemia: prognostic significance.

    Science.gov (United States)

    Letouzey, Mathilde; Penther, Dominique; Roche-Lestienne, Catherine; Nelken, Brigitte; Devoldère, Catherine; Vannier, Jean-Pierre; Schneider, Pascale

    2015-02-01

    The dicentric chromosome (9;20) (dic(9;20)) is described in 2 % of childhood B-acute lymphoblastic leukaemia. Fluorescence in situ hybridization (FISH) is the most reliable method to identify dic(9;20) when compared with conventional cytogenetics. To define the prognostic importance of dic(9;20), we evaluated treatment response and patient survival. This was a retrospective study in three French university centres. Patients' clinical and laboratory characteristics and treatment response are described. Nine children with dic(9;20) have been identified since 1995. All patients had at least one poor prognostic feature either among the clinical features, the initial laboratory results or in the initial treatment response: central nervous system involvement (2/9), high median leucocyte count (≥50 G/L) (8/9) and poor response to prednisone (2/9). All patients were in complete cytological remission after induction therapy but only three had a good molecular response with minimal residual disease (MRD) <10(-3). Five out of nine patients relapsed and two died, 4 and 12 months after diagnosis, respectively. The event-free survival rate in this population was 44 % (95 % confidence interval (CI) = 0.09-0.79) and overall survival 78 % (95 % CI = 0.51-1.05). In this population, dic(9;20) is associated with a relatively poor prognosis. Patients showing dic(9;20), whether this cytogenetic abnormality is associated with other poor prognostic factors or not, should be identified at the outset in order to be offered a more intensive treatment protocol.

  8. Non-invasive bioluminescence imaging to monitor the immunological control of a plasmablastic lymphoma-like B cell neoplasia after hematopoietic cell transplantation.

    Directory of Open Access Journals (Sweden)

    Martin Chopra

    Full Text Available To promote cancer research and to develop innovative therapies, refined pre-clinical mouse tumor models that mimic the actual disease in humans are of dire need. A number of neoplasms along the B cell lineage are commonly initiated by a translocation recombining c-myc with the immunoglobulin heavy-chain gene locus. The translocation is modeled in the C.129S1-Igha(tm1(MycJanz/J mouse which has been previously engineered to express c-myc under the control of the endogenous IgH promoter. This transgenic mouse exhibits B cell hyperplasia and develops diverse B cell tumors. We have isolated tumor cells from the spleen of a C.129S1-Igha(tm1(MycJanz/J mouse that spontaneously developed a plasmablastic lymphoma-like disease. These cells were cultured, transduced to express eGFP and firefly luciferase, and gave rise to a highly aggressive, transplantable B cell lymphoma cell line, termed IM380. This model bears several advantages over other models as it is genetically induced and mimics the translocation that is detectable in a number of human B cell lymphomas. The growth of the tumor cells, their dissemination, and response to treatment within immunocompetent hosts can be imaged non-invasively in vivo due to their expression of firefly luciferase. IM380 cells are radioresistant in vivo and mice with established tumors can be allogeneically transplanted to analyze graft-versus-tumor effects of transplanted T cells. Allogeneic hematopoietic stem cell transplantation of tumor-bearing mice results in prolonged survival. These traits make the IM380 model very valuable for the study of B cell lymphoma pathophysiology and for the development of innovative cancer therapies.

  9. A variant at 9p21.3 functionally implicates CDKN2B in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology

    Science.gov (United States)

    Hungate, Eric A.; Vora, Sapana R.; Gamazon, Eric R.; Moriyama, Takaya; Best, Timothy; Hulur, Imge; Lee, Younghee; Evans, Tiffany-Jane; Ellinghaus, Eva; Stanulla, Martin; Rudant, Jéremie; Orsi, Laurent; Clavel, Jacqueline; Milne, Elizabeth; Scott, Rodney J.; Pui, Ching-Hon; Cox, Nancy J.; Loh, Mignon L.; Yang, Jun J.; Skol, Andrew D.; Onel, Kenan

    2016-01-01

    Paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common cancer of childhood, yet little is known about BCP-ALL predisposition. In this study, in 2,187 cases of European ancestry and 5,543 controls, we discover and replicate a locus indexed by rs77728904 at 9p21.3 associated with BCP-ALL susceptibility (Pcombined=3.32 × 10−15, OR=1.72) and independent from rs3731217, the previously reported ALL-associated variant in this region. Of correlated SNPs tagged by this locus, only rs662463 is significant in African Americans, suggesting it is a plausible causative variant. Functional analysis shows that rs662463 is a cis-eQTL for CDKN2B, with the risk allele associated with lower expression, and suggests that rs662463 influences BCP-ALL risk by regulating CDKN2B expression through CEBPB signalling. Functional analysis of rs3731217 suggests it is associated with BCP-ALL by acting within a splicing regulatory element determining CDKN2A exon 3 usage (P=0.01). These findings provide new insights into the critical role of the CDKN2 locus in BCP-ALL aetiology. PMID:26868379

  10. Factors predicting long-term survival in low-risk diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael B; Pedersen, Niels T; Christensen, Bjarne E

    2003-01-01

    population-based data from the Danish Lymphoma Group, we analyzed if prognostic clinical pretreatment factors could be identified in patients with low-risk DLBCL. One hundred seventy-seven patients, all with a prognostic profile as favorable as possible according to the IPI and treated with anthracycline-based...... combination chemotherapy (92%) or loco-regional radiotherapy/surgery (8%) with curative intent were included. The median age was 50 years and 170 achieved complete remission. The median follow-up time was 11 years. Twenty-six patients relapsed, with a median time to relapse of 12.1 months. Overall survival...... at 5 years and 10 years was 85% and 75%, respectively. Stage II was associated with poor response to treatment (P=0.044). In a multivariate analysis, Stage II (P=0.001) and age >50 years (P=0.043) were independently associated with poor outcome. Patients without these adverse factors had an excellent...

  11. Ratios of Four STAT3 Splice Variants in Human Eosinophils and Diffuse Large B Cell Lymphoma Cells.

    Science.gov (United States)

    Turton, Keren B; Annis, Douglas S; Rui, Lixin; Esnault, Stephane; Mosher, Deane F

    2015-01-01

    Signal transducer and activator of transcription 3 (STAT3) is a key mediator of leukocyte differentiation and proliferation. The 3' end of STAT3 transcripts is subject to two alternative splicing events. One results in either full-length STAT3α or in STAT3β, which lacks part of the C-terminal transactivation domain. The other is at a tandem donor (5') splice site and results in the codon for Ser-701 being included (S) or excluded (ΔS). Despite the proximity of Ser-701 to the site of activating phosphorylation at Tyr-705, ΔS/S splicing has barely been studied. Sequencing of cDNA from purified eosinophils revealed the presence of four transcripts (S-α, ΔS-α, S-β, and ΔS-β) rather than the three reported in publically available databases from which ΔS-β is missing. To gain insight into regulation of the two alternative splicing events, we developed a quantitative(q) PCR protocol to compare transcript ratios in eosinophils in which STAT3 is upregulated by cytokines, activated B cell diffuse large B cell Lymphoma (DLBCL) cells in which STAT3 is dysregulated, and in germinal center B cell-like DLBCL cells in which it is not. With the exception of one line of activated B cell DLCBL cells, the four variants were found in roughly the same ratios despite differences in total levels of STAT3 transcripts. S-α was the most abundant, followed by S-β. ΔS-α and ΔS-β together comprised 15.6 ± 4.0 % (mean ± SD, n = 21) of the total. The percentage of STAT3β variants that were ΔS was 1.5-fold greater than of STAT3α variants that were ΔS. Inspection of Illumina's "BodyMap" RNA-Seq database revealed that the ΔS variant accounts for 10-26 % of STAT3 transcripts across 16 human tissues, with less variation than three other genes with the identical tandem donor splice site sequence. Thus, it seems likely that all cells contain the S-α, ΔS-α, S-β, and ΔS-β variants of STAT3.

  12. Ratios of Four STAT3 Splice Variants in Human Eosinophils and Diffuse Large B Cell Lymphoma Cells.

    Directory of Open Access Journals (Sweden)

    Keren B Turton

    Full Text Available Signal transducer and activator of transcription 3 (STAT3 is a key mediator of leukocyte differentiation and proliferation. The 3' end of STAT3 transcripts is subject to two alternative splicing events. One results in either full-length STAT3α or in STAT3β, which lacks part of the C-terminal transactivation domain. The other is at a tandem donor (5' splice site and results in the codon for Ser-701 being included (S or excluded (ΔS. Despite the proximity of Ser-701 to the site of activating phosphorylation at Tyr-705, ΔS/S splicing has barely been studied. Sequencing of cDNA from purified eosinophils revealed the presence of four transcripts (S-α, ΔS-α, S-β, and ΔS-β rather than the three reported in publically available databases from which ΔS-β is missing. To gain insight into regulation of the two alternative splicing events, we developed a quantitative(q PCR protocol to compare transcript ratios in eosinophils in which STAT3 is upregulated by cytokines, activated B cell diffuse large B cell Lymphoma (DLBCL cells in which STAT3 is dysregulated, and in germinal center B cell-like DLBCL cells in which it is not. With the exception of one line of activated B cell DLCBL cells, the four variants were found in roughly the same ratios despite differences in total levels of STAT3 transcripts. S-α was the most abundant, followed by S-β. ΔS-α and ΔS-β together comprised 15.6 ± 4.0 % (mean ± SD, n = 21 of the total. The percentage of STAT3β variants that were ΔS was 1.5-fold greater than of STAT3α variants that were ΔS. Inspection of Illumina's "BodyMap" RNA-Seq database revealed that the ΔS variant accounts for 10-26 % of STAT3 transcripts across 16 human tissues, with less variation than three other genes with the identical tandem donor splice site sequence. Thus, it seems likely that all cells contain the S-α, ΔS-α, S-β, and ΔS-β variants of STAT3.

  13. Clinicopathological study of gene rearrangement and immunohistochemical pattern of primary intracranial diffuse large B-cell lymphomas

    Directory of Open Access Journals (Sweden)

    Han X

    2013-11-01

    Full Text Available We studied the clinicopathological and imaging characteristics of primary intracranial diffuse large B-cell lymphomas (PIC-DLBCL. Imaging, histopathological findings, and immunohistochemical staining characteristics were analyzed, and the immunoglobulin heavy and light chain gene rearrangement of 25 PIC-DLBCL cases was examined. MicroRNA was extracted from 10 cases each of PIC-DLBCL, extracerebral germinal center DLBCL (GC-DLBCL, and extracerebral non-GC-DLBCL (NGC-DLBCL; we conducted chip hybridization and comparatively analyzed the difference among the three. PIC-DLBCLs typically involved no less than two cerebral lobes (10/25; the frontal lobe was affected most often (6/25. Target-shaped structures were observed in all PIC-DLBCLs due to the proliferation of centroblast-like large lymphocytes surrounding the vessels. There was strong and diffuse immunostaining for CD20 and CD79a, and negative immunostaining for CD3, CD5, CD23, and cyclin D1 for all PIC-DLBCLs. The percentage of cells with nuclear positivity for anti-Ki67 antibody ranged 50-90% (mean, 80%. Three, 19, and 22 PIC-DLBCLs were CD10-, Bcl-6-, and melanoma ubiquitous mutated 1-positive, respectively. Twenty-four PIC-DLBCLs were B-cell monoclonal. MicroRNA hybridization showed that 788 PIC-DLBCL microRNAs/segments increased to at least twice of that of NGC-DLBCLs, and 401 PIC-DLBCL microRNAs/segments declined to less than half of that of NGC-DLBCLs. Six hundred and eleven PIC-DLBCL microRNAs/segments increased to at least twice that of GC-DLBCLs, and 229 PIC-DLBCL microRNAs/segments declined to less than half of that in GC-DLBCLs. PIC-DLBCL typically affected multiple sites, tended to occur in older men, arose from activated B cells, had high B-cell monoclonality; its microRNA expression differed from that of NGC-DLBCL and GC-DLBCL.

  14. A Rapid Embryonic Stem Cell-Based Mouse Model for B-cell Lymphomas Driven by Epstein-Barr Virus Protein LMP1

    Science.gov (United States)

    Ba, Zhaoqing; Meng, Fei-Long; Gostissa, Monica; Huang, Pei-Yi; Ke, Qiang; Wang, Zhe; Dao, Mai N.; Fujiwara, Yuko; Rajewsky, Klaus; Baochun, Zhang; Alt, Frederick W.

    2015-01-01

    The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) contributes to oncogenic human B-cell transformation. Mouse B cells conditionally expressing LMP1 are not predisposed to B-cell malignancies, as LMP1-expressing B cells are eliminated by T cells. However, mice with conditional B-cell LMP1 expression and genetic elimination of α/β and γ/δ T cells (“CLT” mice) die early in association with B-cell lymphoproliferation and lymphomagenesis. Generation of CLT mice involves in-breeding multiple independently segregating alleles. Thus, while introduction of additional activating or knock-out mutations into the CLT model is desirable for further B-cell expansion and immunosurveillance studies, doing such experiments by germline breeding is time-consuming, expensive and sometimes unfeasible. To generate a more tractable model, we generated clonal CLT ES cells from CLT embryos and injected them into RAG2-deficient blastocysts to generate chimeric mice, which like germline CLT mice harbor splenic CLT B cells and lack T cells. CLT chimeric mice generated by this RAG2-deficient blastocyst complementation (“RDBC”) approach die rapidly in association with B-cell lymphoproliferation and lymphoma. As CLT lymphomas routinely express the Activation-Induced Cytidine Deaminase (AID) antibody diversifier, we tested potential AID roles by eliminating the AID gene in CLT ES cells and testing them via RDBC. We found that CLT and AID-deficient CLT ES chimeras had indistinguishable phenotypes, showing that AID is not essential for LMP1-induced lymphomagenesis. Beyond expanding accessibility and utility of CLT mice as a cancer immunotherapy model, our studies provide a new approach for facilitating generation of genetically complex mouse cancer models. PMID:25934172

  15. Diffuse Bone Marrow Uptake of {sup 99m}Tc-MIBI in A Case of Intravascular Large B-cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Seung Hwan; Oh, So Won; Paeng, Jin Chul; Paik, Jin Ho; Lee, Dong Soo [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2009-08-15

    Intravascular large B-cell lymphoma (IVLBCL) is a subtype of diffuse large cell lymphoma, characterized by proliferation of lymphoid cells in the intravascular space of various organs without causing a mass effect. Although {sup 18}F-FDG PET is a powerful imaging tool in lymphoma, the usefulness of {sup 18}F-FDG PET in the assessment of IVLBCL is still controversial. {sup 99m}Tc-MIBI, a tumor imaging radiopharmaceutical with a different mechanism from that of {sup 18}F-FDG, has been reported to be also effective in lymphoma. However, there is nearly no report on the efficacy of {sup 99m}Tc-Mibg in the assessment of IVLBCL. We present one case of IVLBCL that showed {sup 99m}Tc-MIBI accumulation in the involved bone marrow as an incidental finding, which was discrepant from that of {sup 18}F-FDG PET.

  16. Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2014-03-20

    Acute Undifferentiated Leukemia; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; L1 Adult Acute Lymphoblastic Leukemia; L1 Childhood Acute Lymphoblastic Leukemia; L2 Adult Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  17. The truncate mutation of Notch2 enhances cell proliferation through activating the NF-κB signal pathway in the diffuse large B-cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Xinxia Zhang

    Full Text Available The Notch2 is a critical membrane receptor for B-cell functions, and also displays various biological roles in lymphoma pathogenesis. In this article, we reported that 3 of 69 (4.3% diffuse large B-cell lymphomas (DLBCLs exhibited a truncate NOTCH2 mutation at the nucleotide 7605 (G/A in the cDNA sequence, which led to partial deletion of the C-terminal of PEST (proline-, glutamic acid-, serine- and threonine-rich domain. The truncate Notch2 activated both the Notch2 and the NF-κB signals and promoted the proliferation of B-cell lymphoma cell lines, including DLBCL and Burkitt's lymphoma cell lines. Moreover, the ectopic proliferation was completely inhibited by ammonium pyrrolidinedithiocarbamate (PDTC, an NF-κB inhibitor. Simultaneously, PDTC also reduced the expression level of Notch2. Based on these results, we conclude that the Notch2 receptor with PEST domain truncation enhances cell proliferation which may be associated with the activation of the Notch2 and the NF-κB signaling. Our results are expected to provide a possible target for new DLBCL therapies by suppressing the Notch2 and the NF-κB signaling.

  18. Cold Autoimmune Hemolytic Anemia due to High-grade non Hodgkin's B cell Lymphoma with Weak Response to Rituximab and Chemotherapy Regimens.

    Science.gov (United States)

    Nazel Khosroshahi, Behzad; Jafari, Mohammad; Vazini, Hossein; Ahmadi, Alireza; Shams, Keivan; Kholoujini, Mahdi

    2015-07-01

    Autoimmune hemolytic anemia (AIHA) is characterized by shortening of red blood cell (RBC) survival and the presence of autoantibodies directed against autologous RBCs. Approximately 20% of autoimmune hemolytic anemia cases are associated with cold-reactive antibody. About half of patients with AIHA have no underlying associated disease; these cases are termed primary or idiopathic. Secondary cases are associated with underlying diseases or with certain drugs. We report herein a rare case of cold autoimmiune hemolytic anemia due to high-grade non-Hodgkin's lymphoma of B-cell type with weak response to rituximab and chemotherapy regimens. For treatment B cell lymphoma, Due to lack of treatment response, we used chemotherapy regimens including R- CHOP for the first time, and then Hyper CVAD, R- ICE and ESHAP were administered, respectively. For treatment of autoimmune hemolytic anemia, we have used the corticosteroid, rituximab, plasmapheresis and blood transfusion and splenectomy. In spite of all attempts, the patient died of anemia and aggressive lymphoma nine months after diagnosis. To our knowledge, this is a rare report from cold autoimmune hemolytic anemia in combination with high-grade non-Hodgkin's lymphoma of B-cell type that is refractory to conventional therapies.

  19. DNA methyltransferase DNMT3b protein overexpression as a prognostic factor in patients with diffuse large B-cell lymphomas.

    Science.gov (United States)

    Amara, Khaled; Ziadi, Sonia; Hachana, Mohamed; Soltani, Nabil; Korbi, Sadok; Trimeche, Mounir

    2010-07-01

    Diffuse large B-cell lymphomas (DLBCL) are the most common type of aggressive lymphomas, with considerable heterogeneity in clinical presentation, molecular characteristics, and outcome. Previous studies have showed significant correlations between DNA methyltransferase (DNMT) overexpression and unfavorable prognosis in human cancers. Therefore, we investigated in this study the biological and prognostic significance of DNMT1, DNMT3a, and DNMT3b protein expression in DLBCL. DNA methyltransferase (DNMT) expression was analyzed by immunohistochemistry in 81 DLBCL cases and correlated with clinicopathological parameters. Kaplan-Meier curves were used to estimate survival rates, and the Cox proportional hazard regression model was used to evaluate the prognostic impact of DNMT expression. Our results showed that overexpression of DNMT1, DNMT3a, and DNMT3b were detected in 48%, 13%, and 45% of investigated cases, respectively. DNA methyltransferase 1 (DNMT1) and DNMT3b overexpression was significantly correlated with advanced clinical stages (P = 0.028 and P = 0.016, respectively). Moreover, concomitant expression of DNMT1 and DNMT3b was significantly correlated with resistance to treatment (P = 0.015). With regard to survival rates, although data was available only for 40 patients, DNMT3b overexpression was significantly correlated with shorter overall survival (P = 0.006) and progression-free survival (P = 0.016). Interestingly, multivariate analysis demonstrated that DNMT3b overexpression was an independent prognostic factor for predicting shortened overall survival (P = 0.004) and progression-free survival (P = 0.024). In conclusion, DNMT3b overexpression was identified as an independent prognostic factor for predicting shortened survival of patients with DLBCL and could be, therefore, useful in identifying patients who would benefit from aggressive therapy.

  20. Clinical efficacy and safety in relapsed/refractory diffuse large B-cell lymphoma: a systematic literature review.

    Science.gov (United States)

    Colosia, Ann; Njue, Annete; Trask, Peter C; Olivares, Robert; Khan, Shahnaz; Abbe, Adeline; Police, Rachel; Wang, Jianmin; Ruiz-Soto, Rodrigo; Kaye, James A; Awan, Farrukh

    2014-10-01

    This systematic literature review was designed to assess information on the clinical efficacy and safety of interventions used in the treatment of refractory or relapsed diffuse large B-cell lymphoma (R/R DLBCL) and to perform a meta-analysis if possible. We searched databases (PubMed, EMBASE, and Cochrane Library for articles from 1997 to August 2, 2012 reported in English), conference abstracts, bibliographic reference lists, and the ClinicalTrials.gov database for phase II to IV studies with results. Studies had to report on patients with R/R DLBCL who were not eligible to receive high-dose therapy (HDT) with stem cell transplantation (SCT) (autologous or allogeneic). Mixed-type non-Hodgkin lymphoma (NHL) studies were required to report R/R DLBCL outcomes separately. We identified 55 studies that presented outcomes data separately for patients with R/R DLBCL. Of 7 comparative studies, only 4 were randomized controlled trials (RCTs). In the 2 RCTs with a common regimen, the patient populations differed too greatly to perform a valid meta-analysis. The 48 single-arm studies identified were typically small (n < 50 in most), with 31% reporting median progression-free survival (PFS) or overall survival (OS) specifically for the R/R DLBCL population. In these studies, median OS ranged from 4 to 13 months. The small number of RCTs in R/R DLBCL precludes identifying optimal treatments. Small sample size, infrequent reporting of OS and PFS separated by histologic type, and limited information on patient characteristics also hinder comparison of results. Randomized studies are needed to demonstrate which current therapies have advantages for improving survival and other important clinical outcomes in patients with R/R DLBCL.

  1. Oxidative stress and redox state-regulating enzymes have prognostic relevance in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Peroja Pekka

    2012-03-01

    Full Text Available Abstract Background Oxidative stress and redox-regulating enzymes may have roles both in lymphomagenesis and resistance to lymphoma therapy. Previous studies from the pre-rituximab era suggest that antioxidant enzyme expression is related to prognosis in diffuse large B-cell lymphoma (DLBCL, although these results cannot be extrapolated to patient populations undergoing modern treatment modalities. In this study we assessed expression of the oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG and nitrotyrosine and the antioxidant enzymes thioredoxin (Trx, manganese superoxide dismutase (MnSOD and glutamate-cysteine ligase (GCL via immunohistochemistry in 106 patients with DLBCL. All patients were treated with CHOP-like therapy combined with rituximab. Immunostaining results were correlated with progression-free survival, disease-specific survival and traditional prognostic factors of DLBCL. Results Strong 8-OHdG immunostaining intensity was associated with extranodal involvement (p = 0.00002, a high International Prognostic Index (p = 0.002 and strong Trx (p = 0.011 and GCL (p = 0.0003 expression. Strong Trx staining intensity was associated with poor progression-free survival (p = 0.046 and poor disease-specific survival (p = 0.015. Strong GCL immunostaining intensity predicted poor progression-free survival (p = 0.049. Patients with either strong Trx or strong nitrotyrosine expression showed significantly poorer progression-free survival (p = 0.003 and disease-specific survival (p = 0.031 compared with the other patients. Conclusions The redox state-regulating enzymes GCL and Trx are promising markers in the evaluation of DLBCL prognosis in the era of modern immunochemotherapy.

  2. Lack of topoisomerase copy number changes in patients with de novo and relapsed diffuse large B-cell lymphoma.

    Science.gov (United States)

    Pedersen, Mette Ø; Poulsen, Tim S; Gang, Anne O; Knudsen, Helle; Lauritzen, Anne F; Pedersen, Michael; Nielsen, Signe L; Brown, Peter; Høgdall, Estrid; Nørgaard, Peter

    2015-07-01

    Topoisomerase (TOP) gene copy number changes may predict response to treatment with TOP-targeting drugs in cancer treatment. This was first described in patients with breast cancer and is currently being investigated in other malignant diseases. TOP-targeting drugs may induce TOP gene copy number changes at relapse, with possible implications for relapse therapy efficacy. TOP gene alterations in lymphoma are poorly investigated. In this study, TOP1 and TOP2A gene alterations were investigated in patients with de novo diffuse large B-cell lymphoma (DLBCL) (n = 33) and relapsed DLBCL treated with chemotherapy regimens including TOP2-targeting drugs (n = 16). No TOP1 or TOP2A copy number changes were found. Polysomy of chromosomes 20 and 17 was seen in 3 of 25 patients (12%) and 2 of 32 patients (6%) with de novo DLBCL. Among relapsed patients, chromosome polysomy was more frequently observed in 5 of 13 patients (38%) and 4 of 16 patients (25%) harboring chromosome 20 and 17 polysomy, respectively; however, these differences only tended to be significant (p = 0.09 and p = 0.09, respectively). The results suggest that TOP gene copy number changes are very infrequent in DLBCL and not likely induced by TOP2-targeting drugs. Increased polyploidy of chromosomes 17 and 20 among patients with relapsed DLBCL may reflect genetic compensation in the tumor cells after TOP2 inhibition, but is more likely due to the increased genetic instability often seen in progressed cancers. Therefore, it is unlikely that TOP1 and TOP2A gene alterations can be used as predictive markers for response to treatment with TOP2-targeting drugs in patients with DLBCL.

  3. Treatment and Outcomes in Patients With Primary Cutaneous B-Cell Lymphoma: The BC Cancer Agency Experience

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Sarah N., E-mail: shamilton7@bccancer.bc.ca [University of British Columbia, Vancouver (Canada); Radiation Therapy Program, BC Cancer Agency, Vancouver (Canada); Wai, Elaine S. [Radiation Therapy Program, BC Cancer Agency, Victoria (Canada); Tan, King [Department of Pathology, BC Cancer Agency, Vancouver (Canada); Alexander, Cheryl [Radiation Therapy Program, BC Cancer Agency, Victoria (Canada); Gascoyne, Randy D. [University of British Columbia, Vancouver (Canada); Department of Pathology, BC Cancer Agency, Vancouver (Canada); Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver (Canada); Connors, Joseph M. [University of British Columbia, Vancouver (Canada); Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver (Canada)

    2013-11-15

    Purpose: To review the treatment and outcomes of patients with primary cutaneous B-cell lymphoma (CBCL). Methods and Materials: Clinical characteristics, treatment, and outcomes were analyzed for all patients referred to our institution from 1981 through 2011 with primary CBCL without extracutaneous or distant nodal spread at diagnosis (n=136). Hematopathologists classified 99% of cases using the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) guidelines. Results: Median age at diagnosis was 62 years. Classification was 18% diffuse large B-cell leg-type (DLBCL-leg), 32% follicle center (FCCL), 45% marginal zone (MZL), and 6% nonclassifiable (OTHER). Of the 111 subjects with indolent lymphoma (FCCL, MZL, OTHER), 79% received radiation alone (RT), 11% surgery alone, 3% chemotherapy alone, 4% chemotherapy followed by RT, and 3% observation. Following treatment, 29% of subjects relapsed. In-field recurrence occurred in 2% treated with RT and in 33% treated with surgery alone. Of the 25 subjects with DLBCL-leg, 52% received chemotherapy followed by RT, 24% chemotherapy, 20% RT, and 4% surgery alone. Seventy-nine percent received CHOP-type chemotherapy (cyclophosphamide, doxorubicin or epirubicin, vincristine, prednisone), 47% with rituximab added. Overall and disease-specific survival and time to progression at 5 years were 81%, 92%, and 69% for indolent and 26%, 61%, and 54% for DLBCL-leg, respectively. On Cox regression analysis of indolent subjects, RT was associated with better time to progression (P=.05). RT dose, chemo, age >60 y, and >1 lesion were not significantly associated with time to progression. For DLBCL-leg, disease-specific survival at 5 years was 100% for those receiving rituximab versus 67% for no rituximab (P=.13). Conclusions: This review demonstrates better outcomes for indolent histology compared with DLBCL-leg, validating the prognostic utility of the WHO-EORTC classification. In the indolent group

  4. Obinutuzumab (GA101) for the treatment of chronic lymphocytic leukemia and other B-cell non-hodgkin's lymphomas: a glycoengineered type II CD20 antibody.

    Science.gov (United States)

    Goede, Valentin; Klein, Christian; Stilgenbauer, Stephan

    2015-01-01

    Obinutuzumab (GA101) is a humanized, monoclonal type II CD20 antibody modified by glycoengineering. The glycoengineered Fc portion enhances the binding affinity to the FcγRIII receptor on immune effector cells, resulting in increased antibody-dependent cellular cytotoxicity and phagocytosis. In addition, the type II antibody binding characteristics of obinutuzumab to CD20 lead to an efficient induction of direct non-apoptotic cell death. Preclinical data demonstrated more efficient B-cell depletion in whole blood and superior antitumor activity in xenograft models of obinutuzumab as compared to the type I CD20 antibody rituximab. In previously untreated patients with chronic lymphocytic leukemia (CLL) and comorbidities, obinutuzumab plus chlorambucil increased response rates and prolonged progression-free survival compared with rituximab plus chlorambucil. Obinutuzumab had an acceptable and manageable safety profile, with infusion-related reactions during the first infusion as the most common adverse event. Further phase I/II clinical trials have also shown promising activity in other CD20-positive B-cell non-Hodgkin's lymphomas (NHL). Therefore, several clinical studies are planned or ongoing to investigate obinutuzumab with different combination partners in both untreated and relapsed/refractory patients with different B-cell NHL entities, which in addition to CLL include diffuse large B-cell lymphoma and follicular lymphoma. © 2015 S. Karger GmbH, Freiburg.

  5. Subcellular localization of PUMA regulates its pro-apoptotic activity in Burkitt's lymphoma B cells.

    Science.gov (United States)

    Ambroise, Gorbatchev; Portier, Alain; Roders, Nathalie; Arnoult, Damien; Vazquez, Aimé

    2015-11-10

    The BH3-only protein PUMA (p53-upregulated modulator of apoptosis) is a major regulator of apoptosis. It belongs to the Bcl-2 family of proteins responsible for maintaining mitochondrial outer membrane integrity by controlling the intrinsic (mitochondrial) apoptotic pathway. We describe here a new pathway regulating PUMA activation through the control of its subcellular distribution. Surprisingly, neither PUMA upregulation in normal activated human B lymphocytes nor high levels of PUMA in Burkitt's lymphoma (BL) were associated with cell death. We show that PUMA is localized to the cytosol in these cells. By contrast, various apoptosis-triggering signals were found to promote the translocation of PUMA to the mitochondria in these cells, leading to their death by apoptosis. This apoptosis was associated with the binding of mitochondrial PUMA to anti-apoptotic members of the Bcl-2 family, such as Bcl-2 and Mcl-1. This translocation was caspase-independent but was prevented by inhibiting or knocking down the expression of the MAPK kinase p38. Our data suggest that the accumulation of PUMA in the cytosol may be important for the participation of this protein in apoptosis without the need for prior transcription. This regulatory pathway may be an important feature of differentiation and tumorigenic processes.

  6. High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2010-08-05

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With T(15;17)(q22;q12); Adult Acute Myeloid Leukemia With T(16;16)(p13;q22); Adult Acute Myeloid Leukemia With T(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Burkitt Lymphoma; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Childhood Acute Promyelocytic Leukemia (M3); Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; De Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-Cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent

  7. B cell differentiation in EBV-positive Burkitt Lymphoma is impaired at post-transcriptional level by miRNA altered expression

    DEFF Research Database (Denmark)

    Leucci, E; Onnis, A; Cocco, M;

    2009-01-01

    Endemic, sporadic and HIV-associated Burkitt lymphoma (BL) all have a B-cell phenotype and a MYC translocation, but a variable association with the Epstein-Barr virus (EBV). However, there is still no satisfactory explanation of how EBV participates in the pathogenesis of BL. A recent investigation...... suggested that EBV-positive and EBV-negative BL have different cells of origin. In particular, according to immunoglobulin gene mutation analysis, EBV-negative BLs may originate from early centroblasts, whereas EBV-positive BLs appear to arise from postgerminal center B cells or memory B cells....... The appearance of a germinal center phenotype in EBV-positive cells might thus derive from a block in B cell differentiation. The exit from the germinal center involves a complex series of events which require the activation of BLIMP-1 and the consequent down-regulation of several target genes.Here, we...

  8. Endocrine Effects of the Treatment for Acute Lymphoblastic Leukemia and Hodgkin’s Lymphoma in Childhood

    NARCIS (Netherlands)

    R.D. van Beek (Robert Diederik)

    2010-01-01

    textabstractOne quarter of all cases of pediatric malignancies is acute Lymphoblastic leukemia (ALL). Per year approximately 4 in 100.000 children are diagnosed with ALL. The disease has a peak incidence between the third and sixth year of life. Predisposing factors for ALL are Down syndrome, Fancon

  9. Primary cutaneous B-cell lymphoma other than marginal zone: clinicopathologic analysis of 161 cases: Comparison with current classification and definition of prognostic markers.

    Science.gov (United States)

    Lucioni, Marco; Berti, Emilio; Arcaini, Luca; Croci, Giorgio A; Maffi, Aldo; Klersy, Catherine; Goteri, Gaia; Tomasini, Carlo; Quaglino, Pietro; Riboni, Roberta; Arra, Mariarosa; Dallera, Elena; Grandi, Vieri; Alaibac, Mauro; Ramponi, Antonio; Rattotti, Sara; Cabras, Maria Giuseppina; Franceschetti, Silvia; Fraternali-Orcioni, Giulio; Zerbinati, Nicola; Onida, Francesco; Ascani, Stefano; Fierro, Maria Teresa; Rupoli, Serena; Gambacorta, Marcello; Zinzani, Pier Luigi; Pimpinelli, Nicola; Santucci, Marco; Paulli, Marco

    2016-10-01

    Categorization of primary cutaneous B-cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus-based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL. Upon the histologic features that are listed in the WHO classification, 96 cases were classified as PCFCCL and 25 as PCDLBCL-LT; 40 further cases did not fit in the former subgroups in terms of cytology and/or architecture, thus were classified as PCDLBCL, not otherwise specified (PCDLBCL-NOS). We assigned all the cases a histogenetic profile, based on the immunohistochemical detection of CD10, BCL6, and MUM1, and a "double hit score" upon positivity for BCL2 and MYC. PCDLBCL-NOS had a clinical presentation more similar to PCFCCL, whereas the histology was more consistent with the picture of a diffuse large B-cell lymphoma, as predominantly composed of centroblasts but with intermixed a reactive infiltrate of small lymphocytes. Its behavior was intermediate between the other two forms, particularly when considering only cases with a "non-germinal B-cell" profile, whereas "germinal center" cases resembled PCFCCL. Our data confirmed the aggressive behavior of PCDLBC-LT, which often coexpressed MYC and BCL2. The impact of single factors on 5-year survival was documented, particularly histogenetic profile in PCDLBCL and BCL2 translocation in PCFCCL. Our study confirms that a further group-PCDLBCL-NOS-exists, which can be recognized through a careful combination of histopathologic criteria coupled with adequate clinical information.

  10. Routine use of ancillary investigations in staging diffuse large B-cell lymphoma improves the International Prognostic Index (IPI

    Directory of Open Access Journals (Sweden)

    Shadbolt Bruce

    2009-11-01

    Full Text Available Abstract Background The International Prognostic Index (IPI is used to determine prognosis in diffuse large B-cell lymphoma (DLBCL. One of the determinants of IPI is the stage of disease with bone marrow involvement being classified as stage IV. For the IPI, involvement on bone marrow is traditionally defined on the basis of histology with ancillary investigations used only in difficult cases to aid histological diagnosis. This study aimed to determine the effect of the routine use of flow cytometry, immunohistochemistry and molecular studies in bone marrow staging upon the IPI. Results Bone marrow trephines of 156 histologically proven DLBCL cases at initial diagnosis were assessed on routine histology, and immunohistochemistry using two T-cell markers (CD45RO and CD3, two B-cell markers (CD20 and CD79a and kappa and lambda light chains. Raw flow cytometry data on all samples were reanalysed and reinterpreted blindly. DNA extracted from archived paraffin-embedded trephine biopsy samples was used for immunoglobulin heavy chain and light chain gene rearrangement analysis. Using immunophenotyping (flow cytometry and immunohistochemistry, 30 (19.2% cases were upstaged to stage IV. A further 8 (5.1% cases were upstaged using molecular studies. A change in IPI was noted in 18 cases (11.5% on immunophenotyping alone, and 22 (14.1% cases on immunophenotyping and molecular testing. Comparison of two revised IPI models, 1 using immunophenotyping alone, and 2 using immunophenotyping with molecular studies, was performed with baseline IPI using a Cox regression model. It showed that the revised IPI model using immunophenotyping provides the best differentiation between the IPI categories. Conclusion Improved bone marrow staging using flow cytometry and immunohistochemistry improves the predictive value of the IPI in patients with DLBCL and should be performed routinely in all cases.

  11. Whole exome sequencing of relapsed/refractory patients expands the repertoire of somatic mutations in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Mareschal, Sylvain; Dubois, Sydney; Viailly, Pierre-Julien; Bertrand, Philippe; Bohers, Elodie; Maingonnat, Catherine; Jaïs, Jean-Philippe; Tesson, Bruno; Ruminy, Philippe; Peyrouze, Pauline; Copie-Bergman, Christiane; Fest, Thierry; Jo Molina, Thierry; Haioun, Corinne; Salles, Gilles; Tilly, Hervé; Lecroq, Thierry; Leroy, Karen; Jardin, Fabrice

    2016-03-01

    Despite the many efforts already spent to enumerate somatic mutations in diffuse large B-cell lymphoma (DLBCL), previous whole-genome and whole-exome studies conducted on patients of mixed outcomes failed at characterizing the 30% of patients who will relapse or resist current immunochemotherapies. To address this issue, we performed whole-exome sequencing of normal/tumoral DNA pairs in 14 relapsed/refractory (R/R) patients subclassified by full-transcriptome arrays (six activated B-cell like, three germinal center B-cell like, and five primary mediastinal B-cell lymphomas), from the LNH-03 LYSA clinical trial program. Aside from well-known DLBCL features, gene and pathway level recurrence analyses proposed several interesting leads including TBL1XR1 and activating mutations in IRF4 or in the insulin regulation pathway. Sequencing-based copy number analysis defined 23 short recurrently altered regions involving genes such as REL, CDKN2A, HYAL2, and TP53. Moreover, it highlighted mutations in genes such as GNA13, CARD11, MFHAS1, and PCLO as associated with secondary variant allele amplification events. The five primary mediastinal B-cell lymphomas (PMBL), while unexpected in a R/R cohort, showed a significantly higher mutation rate (P = 0.003) and provided many insights on this classical Hodgkin lymphoma related subtype. Novel genes such as XPO1, MFHAS1, and ITPKB were found particularly mutated, along with various cytokine-based signaling pathways. Among these analyses, somatic events in the NF-κB pathway were found preponderant in the three DLBCL subtypes, confirming its major implication in DLBCL aggressiveness and pinpointing several new candidate genes.

  12. Long-term survival of diffuse large B cell lymphoma of the trigeminal region extending to the Meckel's cave treated by CHASER therapy: case report.

    Science.gov (United States)

    Tanaka, Toshihide; Kato, Naoki; Itoh, Kuniaki; Hasegawa, Yuzuru

    2014-01-01

    A 52-year-old man with a history of malignant lymphoma of the cecum presented with lancinating facial pain in the left. Magnetic resonance imaging (MRI) revealed a tumor in the Meckel's cave extending along the trigeminal nerve. The tumor was partially removed via left retrosigmoid lateral suboccipital craniotomy. Histological examination showed findings consistent with diffuse large B cell lymphoma, which was later confirmed to be metastatic lesion from the cecal lesion. Postoperative chemotherapy with cyclophosphamide, high dose, cytarabine, steroid (dexamethasone), etoposide, and rituximab (CHASER) followed by whole brain irradiation (30 Gy) resulted in complete remission. Although facial pain persisted, the patient's general condition remained favorable and he did not experience recurrence over the 51-month follow-up period. Histological confirmation and awareness of malignant lymphoma are very important to determine the therapeutic strategy and to avoid misdiagnosis or delayed diagnosis. Long-term survival of patients with metastatic malignant lymphoma in the Meckel's cave extending along the trigeminal nerve was very rare. In addition, metastatic malignant lymphoma in the extra-axial and peripheral nervous tissue might be different from primary central nervous system lymphoma in the white matter, since the efficacy of chemotherapeutic agents against malignant lymphomas in the extra-axial regions is not attenuated by the blood brain barrier.

  13. Lack of prognostic significance of BCL2 and p53 protein overexpression in elderly patients with diffuse large B-cell non-Hodgkin's lymphoma : Results from a population-based non-Hodgkin's lymphoma registry

    NARCIS (Netherlands)

    Maartense, E; Kramer, MHH; Le Cessie, S; Kluin-Nelemans, JC; Kluin, PM; Snijder, S; Noordijk, EM

    2004-01-01

    The prognostic significance of age was studied in 372 patients with diffuse large B-cell non-Hodgkin's lymphoma, in relation to the prognostic factors of overexpressed BCL2 and p53 oncoprotein. Overexpression of BCL2 and p53 oncoprotein was defined when more than 50% of the tumor cells showed positi

  14. R-CHOEP-14 improves overall survival in young high-risk patients with diffuse large B-cell lymphoma compared with R-CHOP-14. A population-based investigation from the Danish Lymphoma Group

    DEFF Research Database (Denmark)

    Gang, AO; Stroem, C; Pedersen, M;

    2012-01-01

    Background: Optimal treatment of young patients with high-risk diffuse large B-cell lymphoma (DLBCL) remains a matter of debate and requires improvement. The combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with addition of etoposide (CHOEP) has...

  15. The zinc finger SET domain gene Prdm14 is overexpressed in lymphoblastic lymphomas with retroviral insertions at Evi32.

    Directory of Open Access Journals (Sweden)

    E J Dettman

    Full Text Available BACKGROUND: AKXD recombinant inbred strains of mice have proven to be very useful in the identification of potential oncogenes and tumor suppressors involved in the development of lymphoid and myeloid malignancies. In these tumors, the hematopoietic insertion of an active AKV murine leukemia virus (MuLV is associated with the onset of disease. Common sites of retroviral insertion (CIS identify genes causally associated with the development or initiation of lymphoma. METHODOLOGY: In the present study, we analyzed a previously uncharacterized CIS, Ecotropic Viral Integration Site 32 (Evi32, which is located on mouse chromosome 1. We analyzed candidate genes in the region to identify those involved in Evi32 mediated oncogenesis. RESULTS: Here we show that proviral insertion at Evi32 correlates with significant overexpression of a putative transcription factor, PR-domain containing 14 (Prdm14. Tumors with insertions at Evi32 are consistently lymphoid in nature. Prdm14 is normally expressed early in embryonic development with the highest expression in undifferentiated embryonic stem (ES cells. This study implicates Prdm14 as a proto-oncogene involved in lymphoblastic lymphoma formation.

  16. Diffuse large B-cell non Hodgkin's lymphoma in a 65-year-old woman presenting with hypopituitarism and recovering after chemotherapy: a case report

    Directory of Open Access Journals (Sweden)

    Hyer Steve L

    2011-10-01

    Full Text Available Abstract Introduction Diffuse large B-cell non Hodgkin's lymphoma may involve the pituitary either as a primary central nervous system lymphoma or, more frequently, as metastasis from systemic lymphoma leading to hypopituitarism. A partial recovery of pituitary function after treatment with chemotherapy has previously been described but complete recovery with cessation of all hormone supplements is excessively rare. We report a patient presenting with anterior hypopituitarism with subsequent complete and sustained recovery of pituitary function after successful treatment of the lymphoma. Case presentation A 65-year-old Caucasian woman with lethargy, loss of appetite and peripheral edema was found to have anterior hypopituitarism. Magnetic resonance imaging showed no mass lesions in the pituitary although a positron emission tomography scan showed abnormal pituitary activity. An abdominal computed tomography scan revealed multiple intra-abdominal lymph nodes, which on histology proved diagnostic of diffuse large B-cell non Hodgkin's lymphoma. She received six cycles of R-CHOP chemotherapy, after which she achieved a complete metabolic response at all known previous sites of the disease, confirmed by positron emission tomography scanning. Concomitant with the tumor response, there was full recovery of adrenal, thyroid and gonadal axes which has persisted at 10 months follow-up. Conclusion Although rare, it is important to recognize lymphomatous infiltration of the pituitary as a potentially reversible cause of hypopituitarism.

  17. A clinically based prognostic index for diffuse large B-cell lymphoma with a cut-off at 70 years of age significantly improves prognostic stratification

    DEFF Research Database (Denmark)

    Gang, Anne O; Pedersen, Michael; d'Amore, Francesco

    2015-01-01

    The introduction of rituximab and generally improved health among elderly patients have increased the survival of patients with diffuse large B-cell lymphoma (DLBCL). The International Prognostic Index (IPI) from 1992 is based on pre-rituximab data from clinical trials including several lymphoma...... subtypes. We applied IPI factors to a population-based rituximab-treated cohort of 1990 patients diagnosed 2000-2010 and explored new factors and the optimal prognostic age cut-off for DLBCL. Multivariate-analyses (MVA) confirmed the prognostic value of all IPI factors except the presence of > 1 extranodal...

  18. Malignancies, Particularly B-Cell Lymphomas, Are a Frequent Cause of Mortality in Human Immunodeficiency Virus-1 Patients Despite Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Griffin, Daniel O.; Metzger, Michael; Poeth, Kaitlin; Deng, Kathy; Dharsee, Arif; Rico, Juan Carlos; McGowan, Joseph

    2015-01-01

    Human immunodeficiency virus (HIV)-1-infected individuals are affected by diseases at rates above those of their HIV-negative peers despite the increased life expectancy of the highly active antiretroviral therapy era. We followed a cohort of approximately 2000 HIV-1-infected patients for 5 years. The most frequent cause of death in this HIV-1-infected cohort was malignancy, with 39% of all classified deaths due to cancer. Among the cancer deaths, B-cell lymphomas were the most commonly seen malignancy, representing 34% of all cancer deaths. These lymphomas were very aggressive with a median survival of <2 months from time of diagnosis. PMID:26566539

  19. The Spectrum of Kidney Pathology in B-Cell Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma: A 25-Year Multicenter Experience

    Science.gov (United States)

    Poitou-Verkinder, Anne-Laure; Francois, Arnaud; Drieux, Fanny; Lepretre, Stéphane; Legallicier, Bruno; Moulin, Bruno; Godin, Michel; Guerrot, Dominique

    2015-01-01

    Background Chronic lymphocytic leukemia and small lymphocytic lymphoma are 2 different presentations of the most common B-cell neoplasm in western countries (CLL/SLL). In this disease, kidney involvement is usually silent, and is rarely reported in the literature. This study provides a clinicopathological analysis of all-cause kidney disease in CLL/SLL patients. Methods Fifteen CLL/SLL patients with kidney biopsy were identified retrospectively. Demographic, clinical, pathological and laboratory data were assessed at biopsy, and during follow-up. Results At biopsy 11 patients presented impaired renal function, 7 patients nephrotic syndrome, 6 patients dysproteinemia, and 3 patients cryoglobulinemia. Kidney pathology revealed CLL/SLL-specific monoclonal infiltrate in 10 biopsies, glomerulopathy in 9 biopsies (5 membranoproliferative glomerulonephritis, 2 minimal change disease, 1 glomerulonephritis with organized microtubular monoclonal immunoglobulin deposits, 1 AHL amyloidosis). Five patients presented interstitial granulomas attributed to CLL/SLL. After treatment of the hematological disease, improvement of renal function was observed in 7/11 patients, and remission of nephrotic syndrome in 5/7 patients. During follow-up, aggravation of the kidney disease systematically occurred in the absence of favorable response to hematological treatment. Conclusions A broad spectrum of kidney diseases is associated with CLL/SLL. In this setting, kidney biopsy can provide important information for diagnosis and therapeutic guidance. PMID:25811382

  20. Staphylococcus aureus α-toxin triggers the synthesis of B-cell lymphoma 3 by human platelets.

    Science.gov (United States)

    Schubert, Sebastian; Schwertz, Hansjörg; Weyrich, Andrew S; Franks, Zechariah G; Lindemann, Stephan; Otto, Monika; Behr, Hagen; Loppnow, Harald; Schlitt, Axel; Russ, Martin; Presek, Peter; Werdan, Karl; Buerke, Michael

    2011-02-01

    The frequency and severity of bacteremic infections has increased over the last decade and bacterial endovascular infections (i.e., sepsis or endocarditis) are associated with high morbidity and mortality. Bacteria or secreted bacterial products modulate platelet function and, as a result, affect platelet accumulation at sites of vascular infection and inflammation. However, whether bacterial products regulate synthetic events in platelets is not known. In the present study, we determined if prolonged contact with staphylococcal α-toxin signals platelets to synthesize B-cell lymphoma (Bcl-3), a protein that regulates clot retraction in murine and human platelets. We show that α-toxin induced α(IIb)β(3)-dependent aggregation (EC(50) 2.98 µg/mL ± 0.64 µg/mL) and, over time, significantly altered platelet morphology and stimulated de novo accumulation of Bcl-3 protein in platelets. Adherence to collagen or fibrinogen also increased the expression of Bcl-3 protein by platelets. α-toxin altered Bcl-3 protein expression patterns in platelets adherent to collagen, but not fibrinogen. Pretreatment of platelets with inhibitors of protein synthesis or the mammalian Target of Rapamycin (mTOR) decreased Bcl-3 protein expression in α-toxin stimulated platelets. In conclusion, Staphylococcusaureus-derived α-toxin, a pore forming exotoxin, exerts immediate (i.e., aggregation) and prolonged (i.e., protein synthesis) responses in platelets, which may contribute to increased thrombotic events associated with gram-positive sepsis or endocarditis.

  1. Epstein-Barr virus as a prognostic factor in de novo nodal diffuse large B-cell lymphoma.

    Science.gov (United States)

    Morales, Domingo; Beltran, Brady; De Mendoza, Fernando Hurtado; Riva, Luis; Yabar, Alejandro; Quiñones, Pilar; Butera, James N; Castillo, Jorge

    2010-01-01

    Although the International Prognostic Index (IPI) score is a valuable prognostic tool in diffuse large B-cell lymphoma (DLBCL), other risk-stratifying factors may be of value. The aim of this study was to define the prognostic value of EBV expression in de novo nodal DLBCL. Seventy-four cases were selected between January 2002 and December 2007. Clinical data were reviewed and tissue samples were evaluated for expression of CD20, CD10, bcl-6, MUM1, and EBV-encoded RNA (EBER). Of 74 evaluated cases, 53 cases (72%) were of non-germinal center-like subtype and 11 cases (15%) were positive for EBER. In a univariate analysis of the 57 patients who received chemotherapy, factors associated with survival were EBV status, performance status, LDH level, and IPI score. Using a multivariate analysis, a prognostic model was developed using IPI score and EBV status, which showed statistical significance. Our study supports EBV status as a powerful prognostic factor in de novo nodal DLBCL. Prospective studies should be carried to validate this hypothesis.

  2. Pretherapy metabolic tumour volume is an independent predictor of outcome in patients with diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Sasanelli, Myriam; Meignan, Michel; Haioun, Corinne; Itti, Emmanuel [Paris-Est University, Nuclear Medicine and Lymphoid Malignancies Unit, Henri Mondor Hospital, Creteil (France); Berriolo-Riedinger, Alina; Casasnovas, Rene-Olivier [Nuclear Medicine and Hematology, Georges-Francois Leclerc Center, Le Bocage Hospital, Dijon (France); Biggi, Alberto; Gallamini, Andrea [Nuclear Medicine and Hematology, Santa Croce e Carle Hospital, Cuneo (Italy); Siegel, Barry A.; Cashen, Amanda F. [Washington University School of Medicine, Nuclear Medicine and Oncology, Siteman Cancer Center, St. Louis, MO (United States); Vera, Pierre; Tilly, Herve [Nuclear Medicine and Hematology, Henri Becquerel Center, Rouen (France); Versari, Annibale [Nuclear Medicine, Santa Maria Nuova Hospital-IRCCS, Reggio Emilia (Italy)

    2014-11-15

    We investigated the prognostic value of total metabolic tumour volume (TMTV) in diffuse large B-cell lymphoma (DLBCL). TMTV was measured in 114 patients with newly diagnosed DLBCL who underwent {sup 18}F-FDG PET/CT at baseline before immunochemotherapy. TMTV was computed by summing the volumes of all lymphomatous lesions after applying the local SUVmax threshold of 41 % using semiautomatic software. Prognostic value was assessed by Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). Median follow-up was 39 months. Average pretherapy TMTV was 509 ± 568 cm{sup 3}. The 3-year estimates of PFS were 77 % in the low metabolic burden group (TMTV ≤550 cm{sup 3}) and 60 % in the high metabolic burden group (TMTV >550 cm{sup 3}, p = 0.04), and prediction of OS was even better (87 % vs. 60 %, p = 0.0003). Cox regression showed independence of TMTV for OS prediction (p = 0.002) compared with other pretherapy indices of tumour burden, such as tumour bulk and the International Prognostic Index. Pretherapy TMTV is an independent predictor of outcome in patients with DLBCL. (orig.)

  3. Prognostic role of pretreatment neutrophil-lymphocyte ratio in patients with diffuse large B-cell lymphoma treated with RCHOP

    Science.gov (United States)

    Wang, Jing; Zhou, Min; Xu, Jing-Yan; Yang, Yong-Gong; Zhang, Qi-Guo; Zhou, Rong-Fu; Chen, Bing; Ouyang, Jian

    2016-01-01

    Abstract This study aims to investigate whether neutrophil to lymphocyte ratio (NLR) is an independent predictor in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. Data from newly diagnosed DLBCL patients at Nanjing Drum Tower Hospital from 2006 to 2015 were retrospectively reviewed. We used the receiver operating characteristic (ROC) curve analysis to generate the optimal cutoff value for NLR. Among those 156 patients enrolled, the NLR was < 3.0 in 46.8% (73/156) of the patients, and the remaining 53.2% (83/156) had an NLR ≥ 3.0. Patients with higher pretreatment NLR were found to correlate with poorer OS and PFS than these with lower NLR (hazard ratio [HR] = 2.66, 95% confidence interval [CI] = 1.43–4.97, P = 0.002 and HR = 1.79, 95% CI = 1.05–3.07, P = 0.034, respectively). The multivariate Cox proportional hazard model analysis further showed that high NLR was found independently predictive of poor OS (HR = 0.40; CI = 0.19–0.84, P = 0.015) and PFS (HR = 0.57; CI = 0.33–0.98, P = 0.042). Consequently, pretreatment NLR was an independent prognostic predictor in patients with DLBCL in the rituximab era. PMID:27661033

  4. Rapamycin modulated brain-derived neurotrophic factor and B-cell lymphoma 2 to mitigate autism spectrum disorder in rats

    Science.gov (United States)

    Zhang, Jie; Liu, Li-Ming; Ni, Jin-Feng

    2017-01-01

    The number of children suffered from autism spectrum disorder (ASD) is increasing dramatically. However, the etiology of ASD is not well known. This study employed mammalian target of rapamycin inhibitor rapamycin to explore its effect on ASD and provided new therapeutic strategies for ASD. ASD rat model was constructed and valproic acid (VPA) was injected intraperitoneally into rats on pregnancy day 12.5. Offspring from VPA group were divided into ASD group and ASD + rapamycin (ASD + RAPA) group. Compared with normal group, the frequency and duration of social behavior and straight times of ASD group were shortened, but the grooming times were extended. Meanwhile, in ASD group, the average escape latency and the frequency of crossing plates were decreased, the apoptotic index (AI) detected by TUNEL assay was increased, and the expression of brain-derived neurotrophic factor (BDNF) and B-cell lymphoma 2 (Bcl-2) analyzed was decreased with great difference compared with normal group (P<0.01). However, rapamycin treatment in ASD rats mitigated the ASD-like social behavior, such as the frequencies of straight and grooming. Furthermore, rapamycin shortened the average escape latency, but increased the frequency of crossing plates of ASD rats. In hippocampus, rapamycin decreased the AI, but increased the levels of BDNF and Bcl-2 (P<0.01) of ASD rats. These findings revealed that rapamycin significantly mitigated the social behavior by enhancing the expression of BDNF and Bcl-2 to suppress the hippocampus apoptosis in VPA-induced ASD rats.

  5. Clinicopathological Analysis of Pulmonary Marginal Zone B-cell Lymphoma of 
Mucosa-associated Lymphoid Tissue

    Directory of Open Access Journals (Sweden)

    Jing ZENG

    2011-05-01

    Full Text Available Background and objective As a rare disease, pulmonary marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (PMZL-MALT, is often misdiagnosed. The aim of this study is to summarize the clinical and pathological features of this disease and improve the awareness of doctors. Methods Seven cases (female 5, male 2 diagnosed of PMZL-MALT in West China Hospital between November 2008 and November 2010, were analyzed retrospectively, including their symptoms, radiological findings, pathological examinations, treatment and prognosis. Results The median age of the patients were 62 years old (range 34-79 years. Six patients suffered from cough and sputum. Pulmonary consolidation was the most frequent manifestation, leading a misdiagnosis of pneumonia with CT examinations. Pathological diagnosis was obtained via fiberoptic bronchoscopy in six patients and percutaneous pulmonary biopsy for the rest one. In the seven cases, immunohistochemical results showed CD20(+, CD79a(+, while CD3 epsilon(-, CD5(-, CyclinD1(-, CD10(-, Bcl-2(- and CD30(-. Additionally, the expression of Ki-67 was below 10%. Further PCR analysis showed evidence of immunoglobulin heavy chain gene rearrangement in tissues from six subjects. Based on the disease location and patients’ wishes, compared with two cases just receiving symptomatic treatments, the other five ones took in chemotherapies. Conclusion Since there were no specific clinical features for patients of PMZL-MALT, histopathological examination was the only effective means to confirm the diagnosis.

  6. Vav-1 expression correlates with NFkappaB activation and CD40-mediated cell death in diffuse large B-cell lymphoma cell lines

    DEFF Research Database (Denmark)

    Hollmann, Annette; Aloyz, Raquel; Baker, Kristi;

    2010-01-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with a variable response to therapy. We have previously shown that DLBCL cell lines differ in their susceptibility to CD40-mediated cell death, and that resistance to CD40-targeted antibodies correlated with increased expression...... of markers of immature B-cell and absence of Vav-1 mRNA. We used gene expression profiling to investigate the mechanism of CD40 resistance in these cell lines, and found that resistance correlated with lack of Vav-1 and inability to activate NFkappaB upon CD40 ligation. Analysis of tissue microarrays of 213...

  7. Critical role of PI3K signaling for NF-kappaB-dependent survival in a subset of activated B-cell-like diffuse large B-cell lymphoma cells.

    Science.gov (United States)

    Kloo, Bernhard; Nagel, Daniel; Pfeifer, Matthias; Grau, Michael; Düwel, Michael; Vincendeau, Michelle; Dörken, Bernd; Lenz, Peter; Lenz, Georg; Krappmann, Daniel

    2011-01-04

    The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) represents a very aggressive human lymphoma entity. Constitutive NF-κB activation caused by chronic active B-cell receptor (BCR) signaling is common feature of many ABC DLBCL cells; however, the pathways linking BCR signaling to the NF-κB prosurvival network are largely unknown. Here we report that constitutive activity of PI3K and the downstream kinase PDK1 are essential for the viability of two ABC DLBCL cell lines that carry mutations in the BCR proximal signaling adaptor CD79B. In these cells, PI3K inhibition reduces NF-κB activity and decreases the expression of NF-κB target genes. Furthermore, PI3K and PDK1 are required for maintaining MALT1 protease activity, which promotes survival of the affected ABC DLBCL cells. These results demonstrate a critical function of PI3K-PDK1 signaling upstream of MALT1 protease and NF-κB in distinct ABC DLBCL cells and provide a rationale for the pharmacologic use of PI3K inhibitors in DLBCL therapy.

  8. Constitutive activation of extracellular signal-regulated kinase predisposes diffuse large B-cell lymphoma cell lines to CD40-mediated cell death

    DEFF Research Database (Denmark)

    Hollmann, C Annette; Owens, Trevor; Nalbantoglu, Josephine;

    2006-01-01

    CD40 promotes survival, proliferation, and differentiation of normal B cells but can cause activation-induced cell death in malignant B lymphocytes. CD40 ligand and anti-CD40 antibodies have been used successfully to induce apoptosis in lymphoma lines both in vitro and in xenograft tumor models...... a specific cell line or tumor will undergo apoptosis when stimulated with CD40 and to identify targets downstream of CD40 that affect only the apoptotic arm of CD40 signaling. We have analyzed gene expression patterns in CD40-sensitive and CD40-resistant diffuse large B-cell lymphoma (DLBCL) cell lines...... and no increase in ERK activity in response to CD40 stimulation. Our results suggest that constitutive activation of ERK may be required for death signaling by CD40....

  9. A novel orally available inhibitor of focal adhesion signaling increases survival in a xenograft model of diffuse large B-cell lymphoma with central nervous system involvement.

    Science.gov (United States)

    Bosch, Rosa; Moreno, María José; Dieguez-Gonzalez, Rebeca; Céspedes, María Virtudes; Gallardo, Alberto; Trias, Manuel; Grañena, Albert; Sierra, Jorge; Casanova, Isolda; Mangues, Ramon

    2013-08-01

    Central nervous system dissemination is a relatively uncommon but almost always fatal complication in diffuse large B-cell lymphoma patients. Optimal therapy for central nervous involvement in this malignancy has not been established. In this paper, we aimed to evaluate the therapeutic effect of E7123, a celecoxib derivative that inhibits focal adhesion signaling, in a novel xenograft model of diffuse large B-cell lymphoma with central nervous system involvement. Cells obtained after disaggregation of HT subcutaneous tumors (HT-SC cells) were intravenously injected in NOD/SCID mice. These mice received oral vehicle or 75 mg/kg of E7123 daily until they were euthanized for weight loss or signs of sickness. The antitumor effect of E7123 was validated in an independent experiment using a bioluminescent mouse model. Intravenously injected HT-SC cells showed higher take rate and higher central nervous system tropism (associated with increased expression of β1-integrin and p130Cas proteins) than HT cells. The oral administration of E7123 significantly increased survival time in 2 independent experiments using mice injected with unmodified or bioluminescent HT-SC cells. We have developed a new xenograft model of diffuse large B-cell lymphoma with central nervous system involvement that can be used in the pre-clinical evaluation of new drugs for this malignancy. E7123 is a new, well-tolerated and orally available therapeutic agent that merits further investigation since it may improve current management of diffuse large B-cell lymphoma patients with central nervous system involvement.

  10. Pulmonary intravascular large B-cell lymphoma successfully treated with rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone immunochemotherapy: Report of a patient surviving for over 1 year

    OpenAIRE

    NISHII-ITO, SHIZUKA; Izumi, Hiroki; Touge, Hirokazu; TAKEDA, KENICHI; Hosoda, Yuzuru; Yamasaki, Akira; Kuwamoto, Satoshi; Shimizu, Eiji; Motokura, Toru

    2016-01-01

    A 73-year-old man with a history of lethargy, fever and dyspnea was admitted to Tottori University Hospital. A computed tomography (CT) scan revealed splenomegaly and diffusely spreading ground-glass opacities (GGOs) in both lungs. A video-assisted thoracoscopic surgery (VATS)-guided lung biopsy revealed intravascular proliferation of large atypical lymphoid cells in the arteries, veins and alveolar walls. The patient was diagnosed with intravascular large B-cell lymphoma (IVLBCL); he receive...

  11. Primary cutaneous b-cell lymphoma successfully treated with highly active antiretroviral therapy alone: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    María F Villafañe

    2011-01-01

    Full Text Available Cutaneous B-cell lymphoma (CBCL is an unusual skin neoplasm with a great range of clinical presentations. Here, we report a case of CBCL in an AIDS patient presented as a single and nodular/ulcerative lesion in the perianal area. The patient was started on highly active antiretroviral therapy alone with a good clinical and oncological response. Two years later, the patient is asymptomatic with undetectable viral load and immune reconstitution.

  12. High incidence of Kaposi sarcoma-associated herpesvirus infection in HIV-related solid immunoblastic/plasmablastic diffuse large B-cell lymphoma.

    Science.gov (United States)

    Deloose, S T P; Smit, L A; Pals, F T; Kersten, M-J; van Noesel, C J M; Pals, S T

    2005-05-01

    Kaposi sarcoma-associated herpesvirus (KSHV) is known to be associated with two distinct lymphoproliferative disorders: primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD)/MCD-associated plasmablastic lymphoma. We here report a high incidence of KSHV infection in solid HIV-associated immunoblastic/plasmablastic non-Hodgkin's lymphomas (NHLs), in patients lacking effusions and without evidence of (prior) MCD. Within a cohort of 99 HIV-related NHLs, 10 cases were found to be KSHV positive on the basis of immunostaining for KSHV LNA-1 as well as KSHV-specific polymerase chain reaction. All but one of the tumors coexpressed Epstein-Barr virus. Interestingly, all KSHV-positive cases belonged to a distinctive subgroup of 26 diffuse large B-cell lymphomas characterized by the expression of CD138 (syndecan-1) and plasmablastic/immunoblastic morphology. These KSHV-positive lymphomas were preceded by Kaposi sarcoma in 60% of the patients and involved the gastrointestinal tract in 80%. Our results indicate that KSHV infection is not restricted to PEL and MCD; it is also common (38%) in HIV-related solid immunoblastic/plasmablastic lymphomas.

  13. Recurrent mutations of the exportin 1 gene (XPO1) and their impact on selective inhibitor of nuclear export compounds sensitivity in primary mediastinal B-cell lymphoma.

    Science.gov (United States)

    Jardin, Fabrice; Pujals, Anais; Pelletier, Laura; Bohers, Elodie; Camus, Vincent; Mareschal, Sylvain; Dubois, Sydney; Sola, Brigitte; Ochmann, Marlène; Lemonnier, François; Viailly, Pierre-Julien; Bertrand, Philippe; Maingonnat, Catherine; Traverse-Glehen, Alexandra; Gaulard, Philippe; Damotte, Diane; Delarue, Richard; Haioun, Corinne; Argueta, Christian; Landesman, Yosef; Salles, Gilles; Jais, Jean-Philippe; Figeac, Martin; Copie-Bergman, Christiane; Molina, Thierry Jo; Picquenot, Jean Michel; Cornic, Marie; Fest, Thierry; Milpied, Noel; Lemasle, Emilie; Stamatoullas, Aspasia; Moeller, Peter; Dyer, Martin J S; Sundstrom, Christer; Bastard, Christian; Tilly, Hervé; Leroy, Karen

    2016-09-01

    Primary mediastinal B-cell lymphoma (PMBL) is an entity of B-cell lymphoma distinct from the other molecular subtypes of diffuse large B-cell lymphoma (DLBCL). We investigated the prevalence, specificity, and clinical relevance of mutations of XPO1, which encodes a member of the karyopherin-β nuclear transporters, in a large cohort of PMBL. PMBL cases defined histologically or by gene expression profiling (GEP) were sequenced and the XPO1 mutational status was correlated to genetic and clinical characteristics. The XPO1 mutational status was also assessed in DLBCL, Hodgkin lymphoma (HL) and mediastinal gray-zone lymphoma (MGZL).The biological impact of the mutation on Selective Inhibitor of Nuclear Export (SINE) compounds (KPT-185/330) sensitivity was investigated in vitro. XPO1 mutations were present in 28/117 (24%) PMBL cases and in 5/19 (26%) HL cases but absent/rare in MGZL (0/20) or DLBCL (3/197). A higher prevalence (50%) of the recurrent codon 571 variant (p.E571K) was observed in GEP-defined PMBL and was associated with shorter PFS. Age, International Prognostic Index and bulky mass were similar in XPO1 mutant and wild-type cases. KPT-185 induced a dose-dependent decrease in cell proliferation and increased cell-death in PMBL cell lines harboring wild type or XPO1 E571K mutant alleles. Experiments in transfected U2OS cells further confirmed that the XPO1 E571K mutation does not have a drastic impact on KPT-330 binding. To conclude the XPO1 E571K mutation represents a genetic hallmark of the PMBL subtype and serves as a new relevant PMBL biomarker. SINE compounds appear active for both mutated and wild-type protein. Am. J. Hematol. 91:923-930, 2016. © 2016 Wiley Periodicals, Inc.

  14. Bone marrow histopathology in the diagnostic evaluation of splenic marginal-zone and splenic diffuse red pulp small B-cell lymphoma: a reliable substitute for spleen histopathology?

    Science.gov (United States)

    Ponzoni, Maurilio; Kanellis, George; Pouliou, Evi; Baliakas, Panagiotis; Scarfò, Lydia; Ferreri, Andrés J M; Doglioni, Claudio; Bikos, Vasilis; Dagklis, Antonis; Anagnostopoulos, Achilles; Ghia, Paolo; Stamatopoulos, Kostas; Papadaki, Theodora

    2012-11-01

    Primary splenic small B-cell lymphomas mostly comprise the distinct entity of splenic marginal-zone lymphoma (SMZL) and the provisional category of splenic lymphoma/leukemia unclassifiable, mainly represented by the hairy cell leukemia variant and splenic diffuse red pulp small B-cell lymphoma (SDRL). Until recently, histopathologic examination of splenectomy specimens was considered mandatory for the diagnosis of SMZL. However, nowadays, mainly because of advances in chemoimmunotherapy, splenectomy is performed much less frequently. We evaluated the diagnostic efficacy of bone marrow biopsy (BMB) histopathology in the diagnostic approach toward SMZL and SDRL and tested whether it may serve as a substitute for spleen histopathology in the differential diagnosis between these 2 entities. To this end, we conducted a paired assessment of BMB and spleen diagnostic samples from 46 cases with a diagnosis of SMZL (n=32) or SDRL (n=14) based on spleen histopathology. We demonstrate that detailed immunohistopathologic BMB evaluation offers adequate evidence for the confirmation of these entities and their differential diagnosis from other small B-cell lymphoma histotypes. Notably, the immunophenotypical profile of SMZL and SDRL was identical in both BMB and spleen specimens for 21 evaluated markers. Paired assessment of BMB and spleen specimens did not identify discriminating patterns of BMB infiltration, cytology, and/or immunohistology between SMZL and SDRL. Accordingly, bone marrow histopathology contributes significantly in confirming the diagnosis of SMZL and SDRL. However, presently it is not possible to distinguish SMZL from SDRL on the basis of BMB evaluation alone; hence, histopathologic examination of the spleen remains the "gold standard" approach.

  15. Among diffuse large B-cell lymphomas, T-cell-rich/histiocyte-rich BCL and CD30+anaplastic B-cell subtypes exhibit distinct clinical features

    NARCIS (Netherlands)

    Maes, B; Anastasopoulou, A; Kluin-Nelemans, JC; Teodorovic, [No Value; Achten, R; Carbone, A; De Wolf-Peeters, C

    2001-01-01

    Background: The EORTC clinical trial 20901, activated in 1990, was designed to treat non-Hodgkin's lymphomas (NHL) of intermediate/high-grade malignancy according to the Working Formulation. Established in 1994, the R.E.A.L. Classification on NHL has now replaced all former classifications. Patients

  16. Observation of the Curative Effect of Mabthera in Combination with the CHOP Regimen in Treating Invasive B-Cell Lymphoma: A Report of 45 Cases

    Institute of Scientific and Technical Information of China (English)

    Yuerong Shuang; Daqian Ye; Jianxiang Chen; Yaohua Wu; Hui Huang; Guanghua Fan

    2008-01-01

    OBIECTIVE To observe the clinical efficacy and toxic effects of Mabthera(rituximab)in combination with the CHOP(R-CHOP)regimen for treating invasive B-cell non-Hodgkin's lymphoma.METHODS A total of 45 patients with CD20 positive B-cell non-Hodgkin's lymphoma were randomly divided into the R-CHOP(22 cases) and CHOP groups(23 cases for controls).They received the regimens of Mabthera in combination with CHOP or single CHOP therapy respectively.An appraisement of the curative effect could only be performed following 4 cycles of chemotherapy for the 45 patients.Follow-up was conducted to observe the conditions ot survival.RESULTS The rate of complete remission(CR)in the R-CHOP group was 68.2%,with a total effective rate of 81.8%,and in the CHOP group these rates were 34.8% and 78.3%respectively.There was a significant difference in comparing the CR rates between the two groups (P0.05).Adverse effects related to the Mabthera infusions occurred in 6 cases of the R-CHOP group(27.2%).These effects lessened after symptomatic treatment.CONCLUSION The therapeutic regimen Of Mabthera,in combination with CHOP(R-CHOP)has an obvious curative effect for treating invasive B-cell non-Hodgkin's lymphoma,with a favorable tolerance.It is highly recommended as the treatment ot choice.

  17. Activating somatic mutations in diffuse large B-cell lymphomas: lessons from next generation sequencing and key elements in the precision medicine era.

    Science.gov (United States)

    Bohers, Elodie; Mareschal, Sylvain; Bertrand, Philippe; Viailly, Pierre Julien; Dubois, Sydney; Maingonnat, Catherine; Ruminy, Philippe; Tilly, Hervé; Jardin, Fabrice

    2015-05-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma, accounting for 30-40% of newly diagnosed non-Hodgkin lymphomas. Historically, DLBCL has been thought to involve recurrent translocations of the immunoglobulin heavy (IGH) locus and the deregulation of rearranged oncogenes. Whole exome sequencing (WES) of more than 200 DLBCLs has completely redefined the genetic landscape of the disease by identifying recurrent single nucleotide variants and providing new therapeutic opportunities in DLBCL molecular subtypes. Some of these somatic mutations target genes that play a crucial role in B-cell function (B cell receptor [BCR] signaling, nuclear factor κB [NF-κB] pathway, Toll-like receptor [TLR] signaling and phosphatidylinositol 3-kinase [PI3K] pathway), immunity, cell cycle/apoptosis or chromatin modification. In this review, following an overview of the somatic mutations reported in DLBCL, we focus on activating and clustered mutations targeting genes including MYD88, CD79A/B, EZH2 and CARD11 and discuss their clinical and therapeutic relevance in the precision medicine era.

  18. RNA interference-mediated knockdown of brain-derived neurotrophic factor (BDNF) promotes cell cycle arrest and apoptosis in B-cell lymphoma cells.

    Science.gov (United States)

    Xia, D; Li, W; Zhang, L; Qian, H; Yao, S; Qi, X

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin superfamily that has been reported to be involved in a number of neurological and psychological situations. Recently, high expression level of BDNF is observed in diverse human malignancies, delineating a role of BDNF in tumorigenesis. Nevertheless, its effect on B-cell lymphoma remains unclear. In this study, RNA interference technology mediated by short hairpin RNA (shRNA) was performed to inhibit endogenous BDNF expression in B-cell lymphoma cells. Results showed that knockdown of BDNF reduced cell growth and proliferation of Raji and Ramos cells. Furthermore, down-regulation of BDNF induced a cell cycle arrest at G0/G1 phase in Raji cells, and consequently led to cell apoptosis in vitro. Meanwhile, down-regulation of Bcl-2 and up-regulation of Bax, activated caspase-3 and caspase-9 and cleaved poly (ADP-ribose) polymerase (PARP) were observed in Raji cells when endogenous BDNF was inhibited. Besides, we also found that suppression of BDNF in Raji cells increased their sensitivity to chemotherapeutic drug, 5-Fluorouracil (5-FU). Our research provides a promising therapeutic strategy for human B-cell lymphoma by targeting BDNF.

  19. Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2016-08-10

    Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma

  20. Diffuse large B-cell lymphoma: clinical implications of extranodal versus nodal presentation--a population-based study of 1575 cases

    DEFF Research Database (Denmark)

    Møller, Michael B; Pedersen, Niels T; Christensen, Bjarne E

    2004-01-01

    Differences in genetic origin between nodal and extranodal diffuse large B-cell lymphomas (DLBCL) exist. Using population-based data from the registry of the Danish Lymphoma Group, the present study is the first to analyse clinical implications of nodal versus extranodal presentation of DLBCL....... Of 4786 newly diagnosed non-Hodgkin's lymphoma patients in a 16-year period, 1575 (33%) had DLBCL. The annual incidence rate was 2.9 per 100 000; 40% were extranodal. The clinical profile of patients with extranodal DLBCL was different from the nodal DLBCL patients. Extranodal DLBCL was associated...... with older age and poorer performance score, but also lower tumour burden. In extranodal DLBCL, 51% of the cases were stage I and 36% were stage IV, whereas the patients were relatively equally distributed between the four stages in nodal DLBCL. For stage I patients, extranodal DLBCL was independently...

  1. Macrophages in T cell/histiocyte rich large B cell lymphoma strongly express metal-binding proteins and show a bi-activated phenotype.

    Science.gov (United States)

    Hartmann, Sylvia; Tousseyn, Thomas; Döring, Claudia; Flüchter, Patricia; Hackstein, Holger; Herreman, An; Ponzoni, Maurilio; de Wolf-Peeters, Chris; Facchetti, Fabio; Gascoyne, Randy D; Küppers, Ralf; Steidl, Christian; Hansmann, Martin-Leo

    2013-12-01

    Abundant macrophage infiltration in tumors often correlates with a poor prognosis. T cell/histiocyte rich large B cell lymphoma (THRLBCL) is a distinct aggressive B cell lymphoma entity showing a high macrophage content. To further elucidate the role of tumor-associated macrophages in THRLBCL, we performed gene expression profiling of microdissected histiocyte subsets of THRLBCL, nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), Piringer lymphadenitis, sarcoidosis, nonspecific lymphadenitis and monocytes from peripheral blood. In a supervised principal component analysis, histiocytes from THRLBCL were most closely related to epithelioid cells from NLPHL, with both types of cells expressing genes related to proinflammatory and regulatory macrophage activity. Moreover, histiocytes from THRLBCL strongly expressed metal-binding proteins like MT2A, by which histiocytes of THRLBCL can be distinguished from the other histiocyte subsets investigated. Interestingly, the validation at the protein level showed a strong expression of TXN, CXCL9, MT2A and SOD2 not only in macrophages of THRLBCL but also in the tumor cells of NLPHL and classical Hodgkin lymphoma (cHL). Overall, the present findings indicate that macrophages in the microenvironment of THRLBCL have acquired a distinct gene expression pattern that is characterized by a mixed M1/M2 phenotype and a strong expression of several metal binding proteins. The microenvironments in NLPHL and THRLBCL appear to have a similar influence on the macrophage phenotype. The high expression of metal binding proteins in histiocytes of THRLBCL may be diagnostically useful, but a potential pathophysiological role remains to be identified.

  2. Primary diffuse large B-cell lymphoma of the oral cavity Linfoma difuso de grandes células B primário de boca

    Directory of Open Access Journals (Sweden)

    Bruno Correia Jham

    2007-10-01

    Full Text Available Lymphomas arising within the oral cavity account for only 3.5% of all oral malignancies. Diffuse large B-cell lymphoma is a non-Hodgkin lymphoma subtype characterized by diffuse proliferation of large neoplastic B lymphoid cells. This paper reports a case of diffuse large B-cell lymphoma affecting the oral cavity of a Brazilian woman, along with its clinical, microscopical, immunohistochemical, and molecular features.Linfomas correspondem a 3,5% de todos os casos de lesões malignas de boca. O linfoma difuso de grandes células B é um subtipo de linfoma não-Hodgkin caracterizado pela proliferação difusa de células linfóides B. Este artigo relata um caso de linfoma difuso de grandes células B localizado na cavidade bucal de uma mulher brasileira, incluindo os achados clínicos, microscópicos, imuno-histoquímicos e moleculares.

  3. Use of subsequent PET/CT in diffuse large B-cell lymphoma patients in complete remission following primary therapy

    Institute of Scientific and Technical Information of China (English)

    Xu Zhang; Wei Fan; Zhong-Jun Xia; Ying-Ying Hu; Xiao-Ping Lin; Ya-Rui Zhang; Zhi-Ming Li; Pei-Yan Liang; Yuan-Hua Li

    2015-01-01

    Interim 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (I-PET/CT) is a powerful tool for monitoring the response to therapy in diffuse large B-cell lymphoma (DLBCL). This retrospective study aimed to determine when and how to use I-PET/CT in DLBCL. A total of 197 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were enrolled between October 2005 and July 2011; PET/CT was performed at the time of diagnosis (PET/CT0), after 2 and 4 cycles of chemotherapy (PET/CT2 and PET/CT4, respectively), and at the end of treatment (F-PET/CT). According to the International Harmonization Project for Response Criteria in Lymphoma, 110 patients had negative PET/CT2 scans, and 87 had positive PET/CT2 scans. The PET/CT2-negative patients had significantly higher 3-year progression-free survival rate (75.8% vs. 38.2%) and 3-year overal survival rate (93.5%vs. 55.6%) than PET/CT2-positive patients. Al PET/CT2-negative patients remained negative at PET/CT4, but 3 were positive at F-PET/CT. Among the 87 PET/CT2-positive patients, 57 remained positive at F-PET/CT, and 32 progressed during chemotherapy (15 at PET/CT4 and 17 at F-PET/CT). Comparing PET/CT4 with PET/CT0, 7 patients exhibited progression, and 8 achieved partial remission. Comparing F-PET/CT with PET/CT0, 10 patients exhibited progression, and 7 achieved partial remission. In conclusion, our results indicate that I-PET/CT should be performed after 2 rather than 4 cycles of immunochemotherapy in DLBCL patients. There is a limited role for subsequent PET/CT in the detection of relapse in PET/CT2-negative patients, but repeat PET/CT is required if the PET/CT2 findings are positive.

  4. Immunophenotypic features by multiparameter flow cytometry can help distinguish low grade B-cell lymphomas with plasmacytic differentiation from plasma cell proliferative disorders with an unrelated clonal B-cell process.

    Science.gov (United States)

    Rosado, Flavia G; Morice, William G; He, Rong; Howard, Matthew T; Timm, Michael; McPhail, Ellen D

    2015-05-01

    Highly sensitive flow cytometry studies may incidentally identify B cell clones when used to assess plasma cell clonality in bone marrows. Clinical history, which can help differentiate related clones (low grade B cell lymphoma with plasmacytic differentiation/LBCL-PD) from unrelated ones (plasma cell proliferative disorder (PCPD) with an unrelated B cell clone), is often unavailable in referred specimens. We sought to identify morphologic or phenotypic features that would help predict the significance of these clones in the absence of history. We included only cases with identical light chain B and plasma cell clones, as determined by 6-color flow cytometry with additional DNA ploidy analysis, in which the relationship between clones could be established by review of medical records. There were 26 cases; 18 were related (14 were Waldenstrom macroglobulinemia) and eight were unrelated (seven multiple myeloma). Features seen exclusively in LBCL-PD include CD19+/CD45+ clonal plasma cell phenotype (66·7%, P = 0·0022) and morphologic features such as paratrabecular bone marrow involvement, increased mast cells, and plasma cells surrounding B-cell nodules. Aneuploidy was identified exclusively in PCPD cases (75%, P = 0·000028). We conclude that CD19+/CD45+ clonal plasma cell phenotype and aneuploidy are useful in distinguishing related clones (LBCL-PD) from unrelated clones (PCPD).

  5. Importance of gallium-67 scintigraphy in primary cutaneous B-cell lymphoma: report of two cases;Importancia da cintilografia com galio-67 no linfoma cutaneo primario de celulas B: relato de dois casos

    Energy Technology Data Exchange (ETDEWEB)

    Attab, Cyomara Sanches, E-mail: rubinha.attab@terra.com.b [Centro Brasileiro de Medicina Nuclear (CEBRAMEN), Goiania, GO (Brazil); Moriguchi, Sonia Marta [Fundacao Pio XII, Barretos, SP (Brazil). Hospital de Cancer; Paton, Eduardo Jose Alencar [Fundacao Pio XII, Barretos, SP (Brazil). Cancer Hospital. Div. of Hemotherapy and Bone-Marrow Transplant; Alencar, Mario Henrique Leite de [Clinica de Prevencao em Cancer, Goiania, GO, (Brazil); Rocha, Euclides Timoteo da [Fundacao Pio XII, Barretos, SP (Brazil). Cancer Hospital. Dept. of Nuclear Medicine

    2010-05-15

    The authors describe two cases of cutaneous B-cell lymphoma where correct staging, treatment and follow-up could be achieved through a combination of conventional imaging studies and gallium-67 scintigraphy. (author)

  6. High serum vascular endothelial growth factor level is an adverse prognostic factor for high-risk diffuse large B-cell lymphoma patients treated with dose-dense chemoimmunotherapy

    DEFF Research Database (Denmark)

    Riihijärvi, Sari; Nurmi, Heidi; Holte, Harald;

    2012-01-01

    To determine whether serum vascular endothelial growth factor (s-VEGF) levels and VEGF gene expression in tumor tissue predict survival of diffuse large B-cell lymphoma (DLBCL) patients treated with chemoimmunotherapy....

  7. Primary Thymic Extranodal Marginal-Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue Type Exhibits Distinctive Clinicopathological and Molecular Features

    Science.gov (United States)

    Inagaki, Hiroshi; Chan, John K. C.; Ng, Josephine W. M.; Okabe, Mitsukuni; Yoshino, Tadashi; Okamoto, Masataka; Ogawa, Hiroshi; Matsushita, Hiroshi; Yokose, Tomoyuki; Matsuno, Yoshihiro; Nakamura, Naoya; Nagasaka, Tetsuro; Ueda, Ryuzo; Eimoto, Tadaaki; Nakamura, Shigeo

    2002-01-01

    Extranodal marginal-zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT) arising in the thymus is rare, with the largest series in the literature including only three cases. In the present study, we investigated 15 cases of thymic MALT lymphoma to systematically characterize its clinical, histopathological, and molecular features. There was a marked female predilection (male:female = 1:4), with a mean age of 55 years at diagnosis. There was a strong association with autoimmune disease, especially Sjögren’s syndrome. Histologically, the thymic lymphoma showed the characteristic morphological features of extranodal MZBL of MALT type. Cysts were common. Prominent lymphoepithelial lesions were formed by centrocyte-like cells infiltrating and expanding the Hassall’s corpuscles and epithelium lining the cysts. Plasmacytic differentiation was apparent in all cases. Notably, 13 of 15 cases expressed immunoglobulin (Ig) A phenotype; IgA expression in thymic MALT lymphoma was in striking contrast with the IgM phenotype observed in most of the Sjögren’s syndrome-associated MZBLs and MALT lymphomas at other sites. Epstein-Barr virus was absent, and API2-MALT1 gene fusion, a recently reported MALT lymphoma-specific gene abnormality, was not detected in any case. Although one patient died of disease 85 months after the diagnosis, other patients were alive with overall 3-year and 5-year survival rates being 89% and 83%, respectively. Among the 22 patients reported previously and in the present series, at least 17 patients (77%) were Asians. These data indicate that thymic MALT lymphoma may represent a distinct subgroup of MALT lymphoma characterized by apparent predilection for Asians, a strong association with autoimmune disease, frequent presence of cysts, consistent plasma cell differentiation, tumor cells expressing IgA phenotype, and consistent lack of API2-MALT1 gene fusion. PMID:11943727

  8. A case of composite classical and nodular lymphocyte predominant Hodgkin lymphoma with progression to diffuse large B-cell non-Hodgkin lymphoma: Diagnostic difficulty in fine-needle aspiration cytology.

    Science.gov (United States)

    Das, Dilip K; Sheikh, Zafar A; Al-Shama'a, Mariam H; John, Bency; Alawi, Abdulla M S; Junaid, Thamradeen A

    2017-03-01

    A small percentage of nodular lymphocytic predominant Hodgkin lymphoma (NLPHL) progresses to diffuse large B-cell lymphoma (DLBCL). There have also been rare reports of gray zone lymphoma with features intermediate between classical Hodgkin lymphoma (CHL) and DLBCL. We report a very rare case of composite lymphoma (CHL and NLPHL) progressing to DLBCL, and highlight the diagnostic difficulty faced during its fine-needle aspiration (FNA) cytology diagnosis. A 65-year-old woman presented with a right axillary swelling which was subjected to FNA cytology. The routine FNA cytology diagnosis was anaplastic large cell lymphoma (ALCL) but immunocytochemistry did not support this diagnosis completely. The histopathological diagnosis of the excised lymph node was NLPHL with progression to DLBCL in our hospital but in a hospital abroad where the patient was treated, the reviewed diagnosis was CHL. The patient had a rapid downhill course with development of terminal pleural effusion and died approximately one year from initial diagnosis.The review of the cyto-histologic material along with additional immunocyto/histochemical studies and the clinical course of the disease support the diagnosis of a composite lymphoma (CHL and NLPHL) with progression to DLBCL. It is suggested that all the three lesions were clonally related. Diagn. Cytopathol. 2017;45:262-266. © 2016 Wiley Periodicals, Inc.

  9. Aging causes exacerbated ischemic brain injury and failure of sevoflurane post-conditioning: role of B-cell lymphoma-2.

    Science.gov (United States)

    Dong, P; Zhao, J; Zhang, Y; Dong, J; Zhang, L; Li, D; Li, L; Zhang, X; Yang, B; Lei, W

    2014-09-05

    Aging is associated with exacerbated brain injury after ischemic stroke. Herein, we explored the possible mechanisms underlying the age-associated exacerbated brain injury after ischemic stroke and determined whether therapeutic intervention with anesthetic post-conditioning would provide neuroprotection in aged rats. Male Fisher 344 rats (young, 4 months; aged, 24 months) underwent 2h of middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion, with or without sevoflurane post-conditioning for 15 min immediately at the onset of reperfusion. Compared with young rats, aged rats showed larger infarct size, worse neurological scores and more TUNEL-positive cells in the penumbral cerebral cortex at 24h after MCAO. However, edema formation and motor coordination were similar in both groups. Sevoflurane reduced the infarct size, edema formation, and TUNEL-positive cells, and improved the neurological outcome in young rats but not in aged rats. Molecular studies revealed that basal expression of the anti-apoptotic molecule B-cell lymphoma-2 (Bcl-2) in the brain was lower in aged rats compared with young rats before MCAO, while basal expression of the pro-apoptotic molecule Bcl-2-associated X protein (Bax) showed similar levels in both groups. MCAO reduced Bcl-2 expression and increased Bax expression in both groups; however, Bax increase was more pronounced in aged rats. In young rats, sevoflurane reversed the above MCAO-induced changes. In contrast, sevoflurane failed to enhance Bcl-2 expression but decreased Bax expression in aged rats. These findings suggest that aging-associated reduction in basal Bcl-2 expression in the brain contributes to increased neuronal injury by enhancing cell apoptosis after ischemic stroke. Sevoflurane post-conditioning failed to provide neuroprotection in aged rats, probably due to its inability to increase Bcl-2 levels and prevent apoptosis in the brain.

  10. Immunohistochemical and genomic profiles of diffuse large B-cell lymphomas: Implications for targeted EZH2 inhibitor therapy?

    Science.gov (United States)

    Dubois, Sydney; Mareschal, Sylvain; Picquenot, Jean-Michel; Viailly, Pierre-Julien; Bohers, Elodie; Cornic, Marie; Bertrand, Philippe; Veresezan, Elena Liana; Ruminy, Philippe; Maingonnat, Catherine; Marchand, Vinciane; Lanic, Hélène; Penther, Dominique; Bastard, Christian; Tilly, Hervé; Jardin, Fabrice

    2015-01-01

    Enhancer of Zeste Homolog 2 (EZH2) plays an essential epigenetic role in Diffuse Large B Cell Lymphoma (DLBCL) development. Recurrent somatic heterozygous gain-of-function mutations of EZH2 have been identified in DLBCL, most notably affecting tyrosine 641 (Y641), inducing hyper-trimethylation of H3K27 (H3K27me3). Novel EZH2 inhibitors are being tested in phase 1 and 2 clinical trials but no study has examined which patients would most benefit from this treatment. We evaluated the immunohistochemical (IHC) methylation profiles of 82 patients with DLBCL, as well as the mutational profiles of 32 patients with DLBCL using NGS analysis of a panel of 34 genes involved in lymphomagenesis. A novel IHC score based on H3K27me2 and H3K27me3 expression was developed, capable of distinguishing patients with wild-type (WT) EZH2 and patients with EZH2 Y641 mutations (p = 10−5). NGS analysis revealed a subclonal EZH2 mutation pattern in EZH2 mutant patients with WT-like IHC methylation profiles, while associated mutations capable of upregulating EZH2 were detected in WT EZH2 patients with mutant-like IHC methylation profiles. IHC and mutational profiles highlight in vivo hyper-H3K27me3 and hypo-H3K27me2 status, pinpoint associated activating mutations and determine EZH2 mutation clonality, maximizing EZH2 inhibitor potential by identifying patients most likely to benefit from treatment. PMID:25762637

  11. Prognostic value of interim 18F-FDG PET/CT in diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    Zhitao Ying; Xuejuan Wang; Yuqin Song; Wen Zheng; Xiaopei Wang; Yan Xie; Ningjing Lin

    2013-01-01

    Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease.The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL.The prognostic significance of interim PET/CT in DLBCL remains controversial.The aim of this study is to determine the predictive value of interim 18F-FDG PET/CT after first-line treatment in patients with DLBCL.Methods:Thirty-two patients with DLBCL underwent baseline,interim and post-treatment 18F-FDG PET/CT scans.Imaging results were analyzed for the survival of patients via software SPSS 13.0,retrospectively.Results:Thirty-one of the 32 patients were treated with R-CHOP regimen,and interim 18F-FDG PET/CT of 24 patients was performed after 2 cycles of treatment.After a median follow-up period of 16.7 months,the 2-year progression-free survival (PFS) rates were significandy different between the groups above and below SUVmax cut-off value of 2.5 (P=0.039).No significant differences were found in the 2-year PFS rates if SUVmax cut-offvalues were set as 2.0 and 3.0,respectively (P=0.360; P=0.113).Conclusions:Interim PET/CT could predict the prognosis of DLBCL patients with the SUVmax cut-off value of 2.5,but more clinical data should be concluded to confirm this conclusion.

  12. Immunohistochemical and genomic profiles of diffuse large B-cell lymphomas: implications for targeted EZH2 inhibitor therapy?

    Science.gov (United States)

    Dubois, Sydney; Mareschal, Sylvain; Picquenot, Jean-Michel; Viailly, Pierre-Julien; Bohers, Elodie; Cornic, Marie; Bertrand, Philippe; Veresezan, Elena Liana; Ruminy, Philippe; Maingonnat, Catherine; Marchand, Vinciane; Lanic, Hélène; Penther, Dominique; Bastard, Christian; Tilly, Hervé; Jardin, Fabrice

    2015-06-30

    Enhancer of Zeste Homolog 2 (EZH2) plays an essential epigenetic role in Diffuse Large B Cell Lymphoma (DLBCL) development. Recurrent somatic heterozygous gain-of-function mutations of EZH2 have been identified in DLBCL, most notably affecting tyrosine 641 (Y641), inducing hyper-trimethylation of H3K27 (H3K27me3). Novel EZH2 inhibitors are being tested in phase 1 and 2 clinical trials but no study has examined which patients would most benefit from this treatment. We evaluated the immunohistochemical (IHC) methylation profiles of 82 patients with DLBCL, as well as the mutational profiles of 32 patients with DLBCL using NGS analysis of a panel of 34 genes involved in lymphomagenesis. A novel IHC score based on H3K27me2 and H3K27me3 expression was developed, capable of distinguishing patients with wild-type (WT) EZH2 and patients with EZH2 Y641 mutations (p = 10-5). NGS analysis revealed a subclonal EZH2 mutation pattern in EZH2 mutant patients with WT-like IHC methylation profiles, while associated mutations capable of upregulating EZH2 were detected in WT EZH2 patients with mutant-like IHC methylation profiles. IHC and mutational profiles highlight in vivo hyper-H3K27me3 and hypo-H3K27me2 status, pinpoint associated activating mutations and determine EZH2 mutation clonality, maximizing EZH2 inhibitor potential by identifying patients most likely to benefit from treatment.

  13. Immunoglobulin heavy chain/light chain pair measurement is associated with survival in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Jardin, Fabrice; Delfau-Larue, Marie Hélène; Molina, Thierry Jo; Copie-Bergman, Christiane; Brière, Josette; Petrella, Tony; Canioni, Danielle; Fabiani, Bettina; Jais, Jean-Philippe; Figeac, Martin; Leroy, Karen; Mareschal, Sylvain; Salles, Gilles André; Coiffier, Bertrand; Delarue, Richard; Peyrade, Frédéric; Bosly, André; André, Marc; Ketterer, Nicolas; Haioun, Corinne; Tilly, Hervé

    2013-09-01

    Elevated serum free light chains (FLCs) have been associated with an unfavorable prognosis in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to determine the clinical relevance of a quantitative assessment of intact circulating immunoglobulin (Ig), using serum Ig heavy chain/light chain pair (HLC) measurements in patients with DLBCL. FLC and HLC were measured in 409 serum samples of patients with DLBCL included in the LNH03-B clinical trial program of the Groupe d'Etudes des Lymphomes de l'Adulte (GELA). Patients with an abnormal IgMκ/IgMλ ratio or an abnormal FLC ratio more frequently displayed adverse clinical characteristics. Patients with abnormal IgMκ/IgMλ ratios had inferior progression-free survival (PFS) and overall survival (OS) as compared to patients with a normal ratio in the overall cohort (5-year PFS 44.9% vs. 69.3%, p = 0.0003 and 5-year OS 50.8% vs. 78.1%, p = 0.0003) and in the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) cohort (5-year OS 43.5% vs. 70.3%, p = 0.003). In multivariate analysis, including elevated FLC/HLC and International Prognostic Index (IPI), an abnormal IgMκ/IgMλ ratio (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.03-2.3, p = 0.03) remained predictive of shorter progression-free survival. Gene expression profile experiments and immunohistochemistry indicate that this measurement is at least partially related to tumor cell secretion. Both elevated serum FLCs and an abnormal IgMκ/IgMλ ratio are associated with unfavorable outcomes in patients with DLBCL treated by R-CHOP.

  14. Sarcopenia is an independent prognostic factor in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy.

    Science.gov (United States)

    Lanic, Hélène; Kraut-Tauzia, Jerôme; Modzelewski, Romain; Clatot, Florian; Mareschal, Sylvain; Picquenot, Jean Michel; Stamatoullas, Aspasia; Leprêtre, Stéphane; Tilly, Hervé; Jardin, Fabrice

    2014-04-01

    Approximately 25-35% of patients with diffuse large B-cell lymphoma (DLBCL) are older than 70 years. The aim of this study was to investigate the prognostic impact of depletion of skeletal muscle (sarcopenia) in elderly patients with DLBCL. This retrospective analysis included 82 patients with DLBCL older than 70 years and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin, prednisone) or R-miniCHOP. Sarcopenia was measured by the analysis of stored computed tomography (CT) images at the L3 level at baseline. The surface of the muscular tissues was selected according to the CT Hounsfield unit. This value was normalized for stature in order to calculate the lumbar L3 skeletal muscle index (LSMI, in cm(2)/m(2)). The mean age of the population was 78 years. According to the defined cut-offs for LSMI, 45 patients with DLBCL were considered sarcopenic. Sarcopenic patients displayed a higher revised International Prognostic Index (R-IPI) compared with patients without sarcopenia, and were older, with a mean age of 80 years and 77 years, respectively (p = 0.006). With a median follow-up of 39 months, the 2-year overall survival in the sarcopenic population was 46% compared with 84% in the non-sarcopenic group (HR = 3.22; 95% CI = 1.73-5.98; p = 0.0002). In a multivariate analysis, sarcopenia remained predictive of outcome (p = 0.005). Sarcopenia is a relevant and predictive factor in elderly patients with DLBCL treated with rituximab plus chemotherapy.

  15. RelA NF-κB subunit activation as a therapeutic target in diffuse large B-cell lymphoma

    Science.gov (United States)

    Manyam, Ganiraju C.; Visco, Carlo; Tzankov, Alexandar; Wang, Jing; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W.L.; Han van Krieken, J.; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J.M.; Møller, Michael B.; Parsons, Ben M.; Winter, Jane N.; Piris, Miguel A.; Jeffrey Medeiros, L.; Pham, Lan V.; Young, Ken H.

    2016-01-01

    It has been well established that nuclear factor kappa-B (NF-κB) activation is important for tumor cell growth and survival. RelA/p65 and p50 are the most common NF-κB subunits and involved in the classical NF-κB pathway. However, the prognostic and biological significance of RelA/p65 is equivocal in the field. In this study, we assessed RelA/p65 nuclear expression by immunohistochemistry in 487 patients with de novo diffuse large B-cell lymphoma (DLBCL), and studied the effects of molecular and pharmacological inhibition of NF-κB on cell viability. We found RelA/p65 nuclear expression, without associations with other apparent genetic or phenotypic abnormalities, had unfavorable prognostic impact in patients with stage I/II DLBCL. Gene expressionprofiling analysis suggested immune dysregulation and antiapoptosis may be relevant for the poorer prognosis associated with p65 hyperactivation in germinal center B-cell–like (GCB) DLBCL and in activated B-cell–like (ABC) DLBCL, respectively. We knocked down individual NF-κB subunits in representative DLBCL cells in vitro, and found targeting p65 was more effective than targeting other NF-κB subunits in inhibiting cell growth and survival. In summary, RelA/p65 nuclear overexpression correlates with significant poor survival in early-stage DLBCL patients, and therapeutic targeting RelA/p65 is effective in inhibiting proliferation and survival of DLBCL with NF-κB hyperactivation. PMID:27941215

  16. Fli-1 overexpression in hematopoietic progenitors deregulates T cell development and induces pre-T cell lymphoblastic leukaemia/lymphoma.

    Directory of Open Access Journals (Sweden)

    Monique F M A Smeets

    Full Text Available The Ets transcription factor Fli-1 is preferentially expressed in hematopoietic tissues and cells, including immature T cells, but the role of Fli-1 in T cell development has not been closely examined. To address this we retrovirally overexpressed Fli-1 in various in vitro and in vivo settings and analysed its effect on T cell development. We found that Fli-1 overexpression perturbed the DN to DP transition and inhibited CD4 development whilst enhancing CD8 development both in vitro and in vivo. Surprisingly, Fli-1 overexpression in vivo eventuated in development of pre-T cell lymphoblastic leukaemia/lymphoma (pre-T LBL. Known Fli-1 target genes such as the pro-survival Bcl-2 family members were not found to be upregulated. In contrast, we found increased NOTCH1 expression in all Fli-1 T cells and detected Notch1 mutations in all tumours. These data show a novel function for Fli-1 in T cell development and leukaemogenesis and provide a new mouse model of pre-T LBL to identify treatment options that target the Fli-1 and Notch1 signalling pathways.

  17. Effects of microRNA-21 on the biological functions of T-cell acute lymphoblastic lymphoma/leukemia

    Science.gov (United States)

    Shi, Cunzhen; Zhang, Xudong; Li, Xin; Zhang, Lei; Li, Ling; Sun, Zhenchang; Fu, Xiaorui; Wu, Jingjing; Chang, Yu; Li, Wencai; Chen, Qingjiang; Zhang, Mingzhi

    2016-01-01

    Previous studies have demonstrated that microRNA-21 (miR-21) is an oncogene and is significantly upregulated in tumor tissue. However, its association with T-cell acute lymphoblastic lymphoma/leukemia (T-ALL) remains poorly understood. The aim of the present study was to investigate the effects of miR-21 on T-ALL cells by constructing Jurkat cells infected with recombinant adenovirus adv-miR-21 or adv-anti-miR-21. In addition, the target gene of miR-21 was identified by reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that miR-21 expression in Jurkat cells was markedly upregulated. Furthermore, upregulating miR-21 expression in Jurkat cells promoted cell proliferation and invasion and decreased the apoptosis rate. By contrast, knockdown of miR-21 in Jurkat cells suppressed proliferation and invasion and increased the apoptosis rate. Furthermore, the results indicated that signal transducer and activator of transcription (STAT) 3 was targeted by miR-21, and that miR-21 inhibited STAT3 expression at the protein level rather than at the messenger RNA level. In conclusion, targeting the inhibition of miR-21 may be a novel therapeutic strategy for patients with T-ALL. PMID:27895788

  18. Non-Hodgkin lymphoma in the developing world: review of 4539 cases from the International Non-Hodgkin Lymphoma Classification Project.

    Science.gov (United States)

    Perry, Anamarija M; Diebold, Jacques; Nathwani, Bharat N; MacLennan, Kenneth A; Müller-Hermelink, Hans K; Bast, Martin; Boilesen, Eugene; Armitage, James O; Weisenburger, Dennis D

    2016-10-01

    The distribution of non-Hodgkin lymphoma subtypes varies around the world, but a large systematic comparative study has never been done. In this study, we evaluated the clinical features and relative frequencies of non-Hodgkin lymphoma subtypes in five developing regions of the world and compared the findings to the developed world. Five expert hematopathologists classified 4848 consecutive cases of lymphoma from 26 centers in 24 countries using the World Health Organization classification, and 4539 (93.6%) were confirmed to be non-Hodgkin lymphoma, with a significantly greater number of males than females in the developing regions compared to the developed world (Pworld (90.7% and 9.3%, respectively). Also, the developing regions had significantly more cases of high-grade B-cell lymphoma (59.6%) and fewer cases of low-grade B-cell lymphoma (22.7%) compared to the developed world (39.2% and 32.7%, respectively). Among the B-cell lymphomas, diffuse large B-cell lymphoma was the most common subtype (42.5%) in the developing regions. Burkitt lymphoma (2.2%), precursor B- and T-lymphoblastic leukemia/lymphoma (1.1% and 2.9%, respectively) and extranodal natural killer/T-cell lymphoma (2.2%) were also significantly increased in the developing regions. These findings suggest that differences in etiologic and host risk factors are likely responsible, and more detailed epidemiological studies are needed to better understand these differences.

  19. Pharm GKB: Leukemia, B-Cell, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available UTR Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 144 Overview Alternate Names: Synonym Acute... B-Cell Leukemia; Acute B-Cell Leukemias; Acute B-Lymphocytic Leukemia; Acute... B-Lymphocytic Leukemias; Acute lymphoblastic leukaemia, Burkitt's type; Acute lymphoblastic leuka...emia, mature B-cell type; Acute lymphoblastic leukemia, Burkitt's type; Acute lymphoblastic leukemia, mature... B-cell type; B Cell Leukemia, Acute; B Lymphocytic Leukemia, Acute; B-ALL; B-Cell Leukemia, Acute

  20. T-cell-rich large B-cell lymphoma. A study of 30 cases, supporting its histologic heterogeneity and lack of clinical distinctiveness.

    Science.gov (United States)

    Krishnan, J; Wallberg, K; Frizzera, G

    1994-05-01

    To determine whether correlations existed between morphologic and immunophenotypic findings and clinical characteristics, 30 cases of T-cell-rich large B-cell lymphomas (TBL) were evaluated by histopathology, immunostaining, and polymerase chain reaction on paraffin-embedded material. All were characterized by a polymorphic cell composition, including a variable mixture of small and large lymphoid cells and reactive cell. Most cases (87%) fitted into one of three main histologic types of non-Hodgkin's lymphoma (diffuse, mixed cell; diffuse, large cell; follicular and diffuse, mixed cell), and one group of eight cases had the prototypic features described by Ramsay et al. (17). All cases showed a component of large CD20(L26)+ MB2+ B cells in a predominant back-ground of reactive T cells (> 50% of the total lymphoid forms). Clonality was demonstrated by light chain restriction in 67% of cases and by rearrangement of the immunoglobulin heavy chain gene and bcl-2 gene in 64% and 28% of cases, respectively. The patients were predominantly men (70%), ages 18-83 years (median of 62.5), and were initially seen predominantly with nodal disease (and extranodal involvement in 20%) at advanced stages (III-IV: 77%). Treatment was mostly aggressive chemotherapy, and the outcomes were favorable (84% alive and well). These features are not distinctive as compared with those of typical large-cell lymphoma, nor did subgroups within the series (prototypic cases versus others; cases with less [ 70%] T-cell infiltration) significantly differ in clinical presentation or outcome. Thus, this study confirms that TBL, while useful as a diagnostic variant to be distinguished from both peripheral T-cell lymphoma and Hodgkin's disease, is a heterogeneous assortment of diverse histopathologic categories rather than a clinicopathologic entity. The term "T-cell rich" might, however, be usefully retained as a morphologic specification to be added to recognized histologic categories of lymphoma.