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Sample records for chronic myelogenous leukemia

  1. Stages of Chronic Myelogenous Leukemia

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Myelogenous Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Myelogenous Leukemia Go to Health Professional Version Key Points Chronic ...

  2. Chronic myelogenous leukemia (CML)

    Science.gov (United States)

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... nuclear disaster. It takes many years to develop leukemia from radiation exposure. Most people treated for cancer ...

  3. Atypical Chronic Myelogenous Leukemia

    Science.gov (United States)

    ... myeloproliferative neoplasms, leukemia , and other conditions . Chronic Myelomonocytic Leukemia Key Points Chronic myelomonocytic leukemia is a disease ... chance of recovery) and treatment options. Chronic myelomonocytic leukemia is a disease in which too many myelocytes ...

  4. Treatment Options for Chronic Myelogenous Leukemia

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Myelogenous Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Myelogenous Leukemia Go to Health Professional Version Key Points Chronic ...

  5. General Information about Chronic Myelogenous Leukemia

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Myelogenous Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Myelogenous Leukemia Go to Health Professional Version Key Points Chronic ...

  6. Treatment Option Overview (Chronic Myelogenous Leukemia)

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Myelogenous Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Myelogenous Leukemia Go to Health Professional Version Key Points Chronic ...

  7. Allogeneic Transplantation for Patients With Acute Leukemia or Chronic Myelogenous Leukemia (CML)

    Science.gov (United States)

    2016-06-14

    Leukemia, Lymphocytic, Acute; Leukemia; Leukemia Acute Promyelocytic Leukemia (APL); Leukemia Acute Lymphoid Leukemia (ALL); Leukemia Chronic Myelogenous Leukemia (CML); Leukemia Acute Myeloid Leukemia (AML); Leukemia Chronic Lymphocytic Leukemia (CLL)

  8. Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

    Science.gov (United States)

    2015-10-29

    B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  9. Chronic Myelogenous Leukemia (CML) (For Parents)

    Science.gov (United States)

    ... studying the leukemia cells collected from the blood, bone marrow, and/or spinal fluid, doctors can determine the type of leukemia a child has. This is important because treatment varies among different types ... blood or bone marrow, doctors can tell whether the Philadelphia chromosome is ...

  10. Activation of the hedgehog pathway in chronic myelogeneous leukemia patients

    Directory of Open Access Journals (Sweden)

    Long Bing

    2011-01-01

    Full Text Available Abstract Background Hedgehog (Hh signaling pathway is involved in regulation of many tissues development and oncogenesis. Recently, Hh signaling has been identified as a required functional pathway for leukemia stem cells(LSCs, and loss of this pathway impairs leukemia progression. Objectives The aim of this study was to determine the expression of Hedgehog signaling molecules in Chronic Myelogeneous Leukemia (CML patients and normal people by semiquantitative polymerase chain reaction (PCR and to correlate mRNA expression to patients' clinical data. Results Here, we showed that Sonic hedgehog (Shh, Smoothened (Smo, and Gli1 genes of Hh signaling were significantly upregulated in CML patients when compared with normal people (P 0.05. Conclusions These findings suggested that activation of the Hh pathway maybe associated with CML progression. Treatment of CML with imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase inhibitor, has no significant influence on the inhibition of Hh pathway of CML-CP patients.

  11. Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes

    Science.gov (United States)

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); 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 With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); 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 Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  12. Management of Advanced-Phase Chronic Myelogenous Leukemia.

    Science.gov (United States)

    Radich, Jerald P

    2016-05-01

    Chronic myelogenous leukemia represents the poster child of successful precision medicine in cancer, with amazing survival results achieved with targeted tyrosine kinase inhibitors (TKIs) in many patients with chronic-phase disease. Unfortunately, however, this good news has not extended to patients in blast crisis, for whom survival has not clearly been improved with TKIs. During his presentation at the NCCN 21st Annual Conference, Jerald P. Radich, MD, briefly explored the biology behind advanced-stage disease and several of the molecular findings in disease progression. He also reviewed some of the therapeutic options in advanced disease, emphasizing that transplantation, although fraught with some difficulties, offers the best long-term prognosis for patients in blast crisis. PMID:27226510

  13. Spotlight on nilotinib in the treatment of chronic myelogenous leukemia

    Directory of Open Access Journals (Sweden)

    Harnicar S

    2014-08-01

    Full Text Available Stephen Harnicar, Sherry Mathew Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, NY, USA Abstract: Nowhere has targeted therapy been more successful in the hematologic malignancy arena than chronic myelogenous leukemia (CML. By targeting the BCR–ABL fusion oncogene, the introduction of tyrosine-kinase inhibitors (TKIs has dramatically improved the outcomes of this disease. Nilotinib is a second-generation TKI that initially gained approval for the treatment of imatinib-resistant or -intolerant disease for patients with chronic or accelerated-phase CML. Investigation in the first-line setting also demonstrated efficacy, and expanded nilotinib’s approval to include therapy for patients with treatment-naïve chronic-phase CML. Data also exist for blast-phase disease, which allows nilotinib to be an option for all phases. Nilotinib’s place in therapy is continuously being expanded by research in novel areas, such as post-hematopoietic stem cell transplants for prevention of relapse and in the pediatric arena. With multiple TKIs now approved for the treatment of CML, delineating the pharmacologic distinctions of nilotinib is an asset when determining therapy. By understanding the pharmacokinetics and dependence on hepatic metabolism of nilotinib, the clinician can manage the potential toxicities, interactions, and unique dosing of this drug. The recognition of mechanisms of resistance, patient adherence, and cost-effectiveness are similarly significant considerations. Actively integrating these various specifics will allow clinicians to optimize nilotinib therapy for the CML patient. Keywords: nilotinib, chronic myelogenous leukemia, CML, tyrosine-kinase inhibitor, TKI 

  14. On the global dynamics of a chronic myelogenous leukemia model

    Science.gov (United States)

    Krishchenko, Alexander P.; Starkov, Konstantin E.

    2016-04-01

    In this paper we analyze some features of global dynamics of a three-dimensional chronic myelogenous leukemia (CML) model with the help of the stability analysis and the localization method of compact invariant sets. The behavior of CML model is defined by concentrations of three cellpopulations circulating in the blood: naive T cells, effector T cells specific to CML and CML cancer cells. We prove that the dynamics of the CML system around the tumor-free equilibrium point is unstable. Further, we compute ultimate upper bounds for all three cell populations and provide the existence conditions of the positively invariant polytope. One ultimate lower bound is obtained as well. Moreover, we describe the iterative localization procedure for refining localization bounds; this procedure is based on cyclic using of localizing functions. Applying this procedure we obtain conditions under which the internal tumor equilibrium point is globally asymptotically stable. Our theoretical analyses are supplied by results of the numerical simulation.

  15. Sweet′s syndrome in accelerated chronic myelogenous leukemia: A case report and review of literature

    OpenAIRE

    Akhil Kapoor; Surender Beniwal; Satya Narayan; Ashok Kalwar

    2014-01-01

    Sweet′s syndrome (acute febrile neutrophilic dermatosis) is a well documented entity in acute leukemia. However, there have been only rare reports of its association with chronic leukemia. We report a case of sweet′s syndrome in a patient of BCR-ABL positive chronic myelogenous leukemia in accelerated phase for its rare association, classical clinical presentation and dramatic therapeutic response to corticosteroids.

  16. Sweet′s syndrome in accelerated chronic myelogenous leukemia: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Akhil Kapoor

    2014-01-01

    Full Text Available Sweet′s syndrome (acute febrile neutrophilic dermatosis is a well documented entity in acute leukemia. However, there have been only rare reports of its association with chronic leukemia. We report a case of sweet′s syndrome in a patient of BCR-ABL positive chronic myelogenous leukemia in accelerated phase for its rare association, classical clinical presentation and dramatic therapeutic response to corticosteroids.

  17. Acute myelogenous leukemia (AML) - children

    Science.gov (United States)

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  18. A vascular bone necrosis in an untreated case of chronic myelogenous leukemia

    International Nuclear Information System (INIS)

    Hip pain due to aseptic necrosis of the femoral head was the first clinical manifestation of chronic myelogenous leukemia in a 9-year-old white female. An erroneous diagnosis of rheumatoid arthritis was first entertained. Physical examination showed splenomegaly, complete blood count revealed leucocytosis of 359 000. The initial radiograph of the involved hip was negative. Biopsy revealed aseptic necrosis of the femoral head. Chronic myelogenous leukemia (CML) was diagnosed on the basis of the peripheral blood smear and bone marrow biopsy. Two months later, radiograph, radionuclide bone scan, and magnetic resonance imaging (MR) of the involved hip were positive for aseptic necrosis of the femoral head. (orig.)

  19. An adult case of chronic myelogenous leukemia with myeloblastic involvement of the central nervous system.

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    Watanabe,Akiharu

    1984-06-01

    Full Text Available A 31-year-old female with chronic myelogenous leukemia, who developed myeloblastic involvement of the central nervous system during acute myeloblastic transformation of the disease, was treated with methotrexate intrathecally. The therapy produced prompt clinical response and complete reversal of abnormal cerebrospinal fluid findings. However, the patient expired 10 months following the acute blastic crisis.

  20. Inhibitory effects of rapamycin on proliferation of chronic myelogenous leukemia cells and its mechanism

    Institute of Scientific and Technical Information of China (English)

    李杰

    2012-01-01

    Objective To explore the inhibitory effects of rapamycin on proliferation of chronic myelogenous leukemia (CML) cells and its possible mechanism. Methods The effects of rapamycin at various concentrations on cell proliferation of CML cell line K562 cells were analyzed by MTT. The expressions

  1. [Therapy-related chronic myelogenous leukemia following RFM therapy in a patient with follicular lymphoma].

    Science.gov (United States)

    Shibazaki, Mio; Sumi, Masahiko; Takeda, Wataru; Kirihara, Takehiko; Kurihara, Taro; Sato, Keijiro; Ueki, Toshimitsu; Hiroshima, Yuki; Ueno, Mayumi; Ichikawa, Naoaki; Mori, Yuichi; Kobayashi, Hikaru

    2014-08-01

    Therapy-related myelodysplastic syndrome and acute myelogenous leukemia are increasingly being recognized as treatment complications in patients receiving chemotherapy or radiotherapy for previous neoplasms. However, therapy-related chronic myelogenous leukemia is relatively rare. A 61-year-old woman with a history of radiation therapy for breast cancer had previously, in 2007, received 4 courses of chemotherapy (RFM: rituximab, fludarabine, and mitoxantrone) for follicular lymphoma. In 2010, she was diagnosed with chronic-phase chronic myelogenous leukemia (CML) with Philadelphia chromosome but no other cytogenetic anomalies. Although a complete cytogenetic response (CCyR) was achieved with imatinib therapy, she developed leukocytosis with lymphoblasts and lymphoid crisis was diagnosed in January 2013. G-banded karyotyping showed 45, XX, -7, t, (9;22)(q33;q11.2). Unrelated bone marrow stem cell transplantation was performed after she had achieved a CCyR with dasatinib therapy. Polymerase chain reaction detected no major bcr/abl transcript in her bone marrow 42 days after transplantation. The majority of secondary leukemias resulting from the use of cytotoxic drugs can be divided into two well-defined groups depending on whether the patient has received alkylating agents or topoisomerase II inhibitors. However, concerns regarding the leukemogenic potential of fludarabine-based chemotherapy are growing. The potential risk of therapy-related leukemias including CML needs to be considered following fludarabine-based chemotherapy. PMID:25186488

  2. Occurrence of chronic lymphocytic leukemia in patients with chronic myelogenous leukemia

    OpenAIRE

    Bhattacharyya, Pritish K

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia of adults in the western world and constitutes about 33% of all leukemia′s. The incidence of CLL increases with age and are more common in older population. Chronic myeloid leukemia (CML) on the contrary occurs in both young adults and elderly and is a chronic myeloproliferative disease that originates from abnormal pluripotent stem cells and results in involvement of multiple hematopoietic lineages, but predominantly myeloid and ...

  3. Permanent Sensorineural Deafness in a Patient with Chronic Myelogenous Leukemia Secondary to Intracranial Hemorrhage

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    Sakshi Kapur

    2013-01-01

    Full Text Available A 52-year-old male presented with tinnitus and fullness in left ear for one day. Workup revealed a white blood cell count of 685×103/μL with marked increase in granulocyte series and myeloid precursors on peripheral smear. The initial impression was chronic myelogenous leukemia with hyperleukocytosis, and patient was started on hydration, hydroxyurea, and allopurinol. Patient tolerated bone marrow biopsy well but continued to bleed excessively from the biopsy site. Results confirmed Philadelphia chromosome positive chronic myelogenous leukemia (chronic phase. On day three of hospitalization, patient developed sudden slurred speech along with shaking movements involving extremities. Magnetic resonance imaging revealed multiple hemorrhages throughout the brain. Hydroxyurea was continued until insurance coverage for nilotinib was getting approved. On day nine of hospitalization, patient developed sudden bilateral sensorineural deafness. Repeat magnetic resonance imaging revealed multiple new hemorrhages throughout the brain. Computer tomography of the temporal bones showed inflammatory changes in right and left mastoid cells. Nilotinib was started on day eleven of hospitalization. Patient’s white blood cell count continued to decrease, but there was no improvement in hearing. Four months later, patient was treated with bilateral transmastoid cochlear implants. This case highlights permanent deafness as a hemorrhagic complication secondary to chronic myelogenous leukemia.

  4. Role of exosomes released by chronic myelogenous leukemia cells in angiogenesis

    OpenAIRE

    Taverna, S; Flugy Papè, AM; SAIEVA, L; Kohn, EC; A. Santoro; Meraviglia, S; De Leo, G; ALESSANDRO, R

    2011-01-01

    The present study is designed to assess if exosomes released from Chronic Myelogenous Leukemia (CML) cells may modulate angiogenesis. We have isolated and characterized the exosomes generated from LAMA84 CML cells and demonstrated that addition of exosomes to human vascular endothelial cells (HUVEC) induces an increase of both ICAM-1 and VCAM-1 cell adhesion molecules and interleukin-8 expression. The stimulation of cell-cell adhesion molecules was paralleled by a dose-dependent increase of a...

  5. Chronic myelogenous leukemia: molecular monitoring in clinical practice

    Directory of Open Access Journals (Sweden)

    N. R. Ryabchikova

    2013-01-01

    Full Text Available Use of tyrosine kinase inhibitor imatinib has led to significant progress in chronic myeloid leukemia (CML treatment. To date, genetic monitoring is a mandatory attribute of therapy with tyrosine kinase inhibitors. The purpose of this study was to access the imatinib therapy efficacy in CML patients using complete molecular genetic monitoring by standard cytogenetics, realtime polymerase chain reaction and mutational analysis. Correlation between cytogenetic and molecular response was shown. Heterogeneity of molecular response in each patient group was revealed by expression of BCR-ABL. Kinase domain mutations were detected in 32 % of CML patients resistant to imatinib.

  6. Molecular relapse in chronic myelogenous leukemia patients after bone marrow transplantation detected by polymerase chain reaction

    International Nuclear Information System (INIS)

    Relapse of chronic myelogenous leukemia after bone marrow transplantation can be detected by using clinical, cytogenetic, or molecular tools. A modification of the polymerase chain reaction can be used in patients to detect low levels of the BCR-ABL-encoded mRNA transcript, a specific marker for chronic myelogenous leukemia. Early detection of relapse after bone marrow transplantation could potentially alter treatment decisions. The authors prospectively evaluated 19 patients for evidence of molecular relapse, cytogenetic relapse, and clinical relapse after bone marrow transplantation. They used the polymerase chain reaction to detect residual BCR-ABL mRNA in patients followed up to 45 months after treatment and found 4 patients with BCR-ABL mRNA expression following bone marrow transplantation. Fifteen patients did not express detectable BCR-ABL mRNA. All 19 patients remain in clinical remission. In this prospective study of chronic myelogenous leukemia patients treated with bone marrow transplantation, molecular relapse preceded cytogenetic relapse in those patients who persistently express BCR-ABL mRNA. They recommend using standard clinical and cytogenetic testing to make patient care decisions until further follow-up determines the clinical outcome of those patients with residual BCR-ABL mRNA transcripts detected by polymerase chain reaction

  7. Heterogeneity of leukemia-initiating capacity of chronic myelogenous leukemia stem cells.

    Science.gov (United States)

    Zhang, Bin; Li, Ling; Ho, Yinwei; Li, Min; Marcucci, Guido; Tong, Wei; Bhatia, Ravi

    2016-03-01

    Chronic myelogenous leukemia (CML) results from transformation of a long-term hematopoietic stem cell (LTHSC) by expression of the BCR-ABL fusion gene. However, BCR-ABL-expressing LTHSCs are heterogeneous in their capacity as leukemic stem cells (LSCs). Although discrepancies in proliferative, self-renewal, and differentiation properties of normal LTHSCs are being increasingly recognized, the mechanisms underlying heterogeneity of leukemic LTHSCs are poorly understood. Using a CML mouse model, we identified gene expression differences between leukemic and nonleukemic LTHSCs. Expression of the thrombopoietin (THPO) receptor MPL was elevated in leukemic LTHSC populations. Compared with LTHSCs with low MPL expression, LTHSCs with high MPL expression showed enhanced JAK/STAT signaling and proliferation in response to THPO in vitro and increased leukemogenic capacity in vivo. Although both G0 and S phase subpopulations were increased in LTHSCs with high MPL expression, LSC capacity was restricted to quiescent cells. Inhibition of MPL expression in CML LTHSCs reduced THPO-induced JAK/STAT signaling and leukemogenic potential. These same phenotypes were also present in LTHSCs from patients with CML, and patient LTHSCs with high MPL expression had reduced sensitivity to BCR-ABL tyrosine kinase inhibitor treatment but increased sensitivity to JAK inhibitors. Together, our studies identify MPL expression levels as a key determinant of heterogeneous leukemia-initiating capacity and drug sensitivity of CML LTHSCs and suggest that high MPL-expressing CML stem cells are potential targets for therapy. PMID:26878174

  8. Occurrence of chronic lymphocytic leukemia in patients with chronic myelogenous leukemia

    Directory of Open Access Journals (Sweden)

    Pritish K Bhattacharyya

    2013-01-01

    Full Text Available Chronic lymphocytic leukemia (CLL is the most common leukemia of adults in the western world and constitutes about 33% of all leukemia′s. The incidence of CLL increases with age and are more common in older population. Chronic myeloid leukemia (CML on the contrary occurs in both young adults and elderly and is a chronic myeloproliferative disease that originates from abnormal pluripotent stem cells and results in involvement of multiple hematopoietic lineages, but predominantly myeloid and less commonly lymphoid. Association between CLL and myeloid malignancies (CML, acute myeloid leukemia and MDS, myelodysplastic syndrome is rare. In literature documenting CLL and CML in same patients, occur either simultaneously or CML is preceded by CLL.

  9. Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

    Science.gov (United States)

    2016-09-09

    Acute Biphenotypic Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Pancytopenia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Secondary Acute Myeloid Leukemia

  10. Molecular monitoring of BCR-ABL transcripts in patients with chronic myelogenous leukemia: is high sensitivity of clinical value?

    Science.gov (United States)

    Norkin, Maxim; Schiffer, Charles A

    2010-04-01

    Monitoring of disease response during treatment with tyrosine kinase inhibitors of patients with chronic myelogenous leukemia dramatically changed after the introduction of real-time PCR, which allows quantification of BCR-ABL transcript levels with high sensitivity and precision. However, its role in patients who have achieved complete cytogenetic response is not entirely clear; incorrect interpretation of results could lead to unnecessary changes from an effective treatment. This review discusses the current evidence regarding the benefits, uncertainties, and potential drawbacks of molecular monitoring in patients with chronic myelogenous leukemia in chronic phase.

  11. Renal Bleeding Due to Extramedullary Hematopoiesis in a Patient With Chronic Myelogenous Leukemia

    Directory of Open Access Journals (Sweden)

    Stephanie Zettner

    2014-11-01

    Full Text Available Chronic myelogenous leukemia (CML is a myeloproliferative disorder that normally presents in middle-aged adults. Renal infiltration and extramedullary hematopoiesis in renal tissue has been rarely reported. This case report presents a patient with CML and renal insufficiency who developed gross hematuria. Efforts at controlling the hematuria led to a cascade of events propelled by the underlying disorder that ultimately led to a radical nephrectomy, multiorgan failure, and prolonged hospitalization. We suggest that management of gross hematuria in clinically stable patients with CML, suspected of having extramedullary hematopoiesis, should prioritize treatment of the myeloproliferative disorder over efforts to control bleeding.

  12. Update on the management of Philadelphia chromosome positive chronic myelogenous leukemia: role of nilotinib

    Directory of Open Access Journals (Sweden)

    Emole J

    2016-02-01

    Full Text Available Josephine Emole,1 Taiwo Talabi,2 Javier Pinilla-Ibarz1 1Department of Malignant Hematology, 2Moffitt Program for Outreach Wellness Education and Resources, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA Abstract: Chronic myelogenous leukemia (CML is a pluripotent stem cell disease characterized by the presence of the Philadelphia chromosome and the bcr-abl gene. The discovery of tyrosine kinase inhibitors (TKIs revolutionized therapy for CML, such that durable response, increased overall survival, and increased progression-free survival of patients in chronic phase CML is now possible. Due to resistance and intolerance to imatinib, there was need for development of second- and third-generation TKIs for the treatment of CML. This review examines the role of nilotinib, an oral second-generation TKI, in the treatment of Philadelphia positive CML. The pharmacology, efficacy, and safety of nilotinib are critically evaluated. Patient-related issues, including tolerance, drug interactions, and quality of life issues are also examined. Keywords: chronic myelogenous leukemia, nilotinib, tyrosine kinase inhibitor

  13. Group-specific human granulocyte antigens on a chronic myelogenous leukemia cell line with a Philadelphia chromosome marker.

    Science.gov (United States)

    Drew, S I; Terasaki, P I; Billing, R J; Bergh, O J; Minowada, J; Klein, E

    1977-05-01

    Group-specific human granulocyte antigens are serologically detectable with granulocytotoxic-positive human alloantisera on a cell line, K562, of chronic myelogenous leukemia origin which bears a Philadelphia chromosomal marker. The same cell line lacks serologically detectable HLA, B2 microglobulin, and B-lymphocyte antigens. Granulocyte antigens are important cell markers for cell lines of suspected myeloid lineage.

  14. Chronic myelogenous leukemia in chronic phase transforming into acute leukemia under treatment with dasatinib 4 months after diagnosis.

    Science.gov (United States)

    Nakamura, Yukitsugu; Tokita, Katsuya; Nagasawa, Fusako; Takahashi, Wataru; Nakamura, Yuko; Sasaki, Ko; Ichikawa, Motoshi; Mitani, Kinuko

    2016-03-01

    We report a 64-year-old woman morphologically diagnosed with chronic myelogenous leukemia in the chronic phase. Despite having achieved a complete hematological response following treatment with dasatinib, she developed lymphoblastic crisis 4 months later. Blastic cells were in a CD45-negative and SSC-low fraction, and positive for CD10, CD19, CD34, and HLA-DR expression and rearrangement in the immunoglobulin heavy chain gene. Chemotherapy using the HyperCVAD/MA regimen led to a complete cytogenetic response, and after cord blood transplantation, she obtained a complete molecular remission. However, the crisis recurred 6 months later. Another salvage therapy using L-AdVP regimen followed by nilotinib led to a complete molecular remission. Retrospective analyses using flow cytometry and polymerase chain reaction revealed a minimal blastic crisis clone present in the initial marrow in chronic phase. This case is informative as it suggests that sudden blastic crisis may occur from an undetectable blastic clone present at initial diagnosis and that leukemic stem cells may survive cytotoxic chemotherapy that eliminates most of the blastic cells. PMID:26662559

  15. A comprehensive review of occupational and general population cancer risk: 1,3-Butadiene exposure-response modeling for all leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, myeloid neoplasm and lymphoid neoplasm.

    Science.gov (United States)

    Sielken, Robert L; Valdez-Flores, Ciriaco

    2015-11-01

    Excess cancer risks associated with 1,3-butadiene (BD) inhalation exposures are calculated using an extensive data set developed by the University of Alabama at Birmingham (UAB) from an epidemiology study of North American workers in the styrene butadiene rubber (SBR) industry. While the UAB study followed SBR workers, risk calculations can be adapted to estimate both occupational and general population risks. The data from the UAB SBR study offer an opportunity to quantitatively evaluate the association between cumulative exposure to BD and different types of cancer, accounting for the number of tasks involving high-intensity exposures to BD as well as confounding associated with the exposures to the multiple other chemicals in the SBR industry. Quantitative associations of BD exposure and cancer, specifically leukemia, can be further characterized by leukemia type, including potential associations with acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myelogenous leukemia (CML), and the groups of lymphoid and myeloid neoplasms. Collectively, these multiple evaluations lead to a comprehensive analysis that makes use of all of the available information and is consistent with the risk assessment goals of the USEPA and other regulatory agencies, and in line with the recommendations of the USEPA Science Advisory Board. While a range of cancer risk values can result from these multiple factors, a preferred case for occupational and general population risk is highlighted. Cox proportional hazards models are used to fit exposure-response models to the most recent UAB data. The slope of the model with cumulative BD ppm-years as the predictor variable is not statistically significantly greater than zero for CML, AML, or, when any one of eight exposure covariates is added to the model, for all leukemias combined. The slope for CLL is statistically significantly different from zero. The slope for myeloid neoplasms is not statistically

  16. Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era

    DEFF Research Database (Denmark)

    Warlick, Erica; Ahn, Kwang Woo; Pedersen, Tanya L;

    2012-01-01

    Tyrosine kinase inhibitors (TKIs) and reduced intensity conditioning (RIC)/nonmyeloablative (NMA) conditioning hematopoietic cell transplants (HCTs) have changed the therapeutic strategy for chronic myelogenous leukemia (CML) patients. We analyzed post-HCT outcomes of 306 CML patients reported to...

  17. T-lineage blast crisis of chronic myelogenous leukemia: simple record of 4 cases

    Directory of Open Access Journals (Sweden)

    Kartika W. Taroeno-Hariadi

    2005-09-01

    Full Text Available Blast crisis (BC transformation in chronic myelogenous leukemia (CML can involve each differentiation lineage of the hematopoietic system, i.e. granulocyte, monocyte, erythrocyte, megakaryocyte, and lymphocyte lineage. The lymphoid blast crisis (BC leukemia cells usually belong to B-lineage, commonly having the phenotype of Pre-B stage of the B-lineage, in which cell-surface immunoglobulin (sIg is not yet expressed. In contrast, T-lineage BC of CML is extremely rare. The objective of this study is to describe the fenotype, fusion transcript of bcr-abl, TdT, and cytoplasmic CD3 in T-lineage BC CML cases. Case report study. This report shows a simple summary of 4 cases of T-lineage BC of CML which have been collected in the phenotypic and genotypic analysis study for 17 years (1987-2004. In all cases, the chromosomal analysis revealed the presence of t(9;22(q34;q11 at presentation. Cell surface analysis were done at diagnosis. Cases’ mononuclear cells stored as 10% DMSO were retrieved to be performed reverse transcription (RT PCR BCR-ABL multiplex to demonstrate the presence of the fusion transcript of bcr-abl. RT-PCR was also performed for detecting the expression of cytoplasmic CD3ε and terminal deoxynucleotydil transferase (TdT. The results of cell surface antigen (CSA at presentation showed that 1 case was CD7+, CD5-, and CD2-; 1 case CD7+, CD5+, and CD2-; and 2 cases CD7+, CD5+ and CD2+ indicating that all these T-lineage BC of CML cells show the phenotype of pre-(pro- thymic stage phenotype. In the present study, two cases showed b2a2, one e1a2, and one negative bcr-abl transcript. The RT-PCR revealed the presence of CD3ε mRNA in all cases, and TdT mRNA in only one case. These results can constitute a basis for the future analysis of T-lineage BC of CML from now on. (Med J Indones 2005; 14: 184-9Keywords: chronic myelogenous leukemia (CML, blastic crisis (BC, T-lineage, bcr-abl fusion gene, CDε, TdT

  18. Lapatinib induces autophagy, apoptosis and megakaryocytic differentiation in chronic myelogenous leukemia K562 cells.

    Directory of Open Access Journals (Sweden)

    Huey-Lan Huang

    Full Text Available Lapatinib is an oral, small-molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptors (EGFR, or ErbB/Her in solid tumors. Little is known about the effect of lapatinib on leukemia. Using human chronic myelogenous leukemia (CML K562 cells as an experimental model, we found that lapatinib simultaneously induced morphological changes resembling apoptosis, autophagy, and megakaryocytic differentiation. Lapatinib-induced apoptosis was accompanied by a decrease in mitochondrial transmembrane potential and was attenuated by the pancaspase inhibitor z-VAD-fmk, indicating a mitochondria-mediated and caspase-dependent pathway. Lapatinib-induced autophagic cell death was verified by LC3-II conversion, and upregulation of Beclin-1. Further, autophagy inhibitor 3-methyladenine as well as autophagy-related proteins Beclin-1 (ATG6, ATG7, and ATG5 shRNA knockdown rescued the cells from lapatinib-induced growth inhibition. A moderate number of lapatinib-treated K562 cells exhibited features of megakaryocytic differentiation. In summary, lapatinib inhibited viability and induced multiple cellular events including apoptosis, autophagic cell death, and megakaryocytic differentiation in human CML K562 cells. This distinct activity of lapatinib against CML cells suggests potential for lapatinib as a therapeutic agent for treatment of CML. Further validation of lapatinib activity in vivo is warranted.

  19. Overexpression of P-glycoprotein induces acquired resistance to imatinib in chronic myelogenous leukemia cells

    Institute of Scientific and Technical Information of China (English)

    Xing-Xiang Peng; Amit K. Tiwari; Hsiang-Chun Wu; Zhe-Sheng Chen

    2012-01-01

    Imatinib,a breakpoint cluster region (BCR)-Abelson murine leukemia (ABL) tyrosine kinase inhibitor (TKI),has revolutionized the treatment of chronic myelogenous leukemia (CML).However,development of multidrug resistance(MDR) limits the use of imatinib.In the present study,we aimed to investigate the mechanisms of cellular resistance to imatinib in CML.Therefore,we established an imatinib-resistant human CML cell line (K562-imatinib) through a stepwise selection process.While characterizing the phenotype of these cells,we found that K562-imatinib cells were 124.6-fold more resistant to imatinib than parental K562 cells.In addition,these cells were cross-resistant to second- and third-generation BCR-ABL TKIs.Western blot analysis and reverse transcription-polymerase chain reaction(RT-PCR) demonstrated that P-glycoprotein (P-gp) and MDR1 mRNA levels were increased in K562-imatinib cells.In addition,accumulation of [14C]6-mercaptopurine (6-MP) was decreased,whereas the ATP-dependent efflux of [14C] 6-MP and [3H]methotrexate transport were increased in K562-imatinib cells.These data suggest that the overexpression of P-gp may play a crucial role in acquired resistance to imatinib in CML K562-imatinib cells.

  20. Total Body Irradiation for Allogeneic Bone Marrow Transplantation in Chronic Myelogenous Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Su Mi; Choi, Ihl Bohng; Kang, Ki Mun; Kim, In Ah; Shinn, Kyung Sub; Kim, Choon Choo; Kim, Dong Jip [Catholic University College of Medicine, Seoul (Korea, Republic of)

    1994-06-15

    Between July 1987 and December 1992, we treated 22 patients with chromic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation (TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6 fractions/3 days (6 patients) or 1320 cGy/8 fractions/4 days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were 58.5% and 41.2%, respectively, and the relapse rate was 36% among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase (76% vs 33%, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation (50% vs 0%, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase.

  1. Histological and In Vivo Microscopic Analysis of the Bone Marrow Microenvironment in a Murine Model of Chronic Myelogenous Leukemia.

    Science.gov (United States)

    Weissenberger, Eva S; Krause, Daniela S

    2016-01-01

    Imaging of the leukemic bone marrow microenvironment, also called the leukemic bone marrow niche, is an essential method to determine and to evaluate the progression of chronic myelogenous leukemia (CML) and other leukemias in murine models. In this chapter we introduce the murine model of CML primarily used in our laboratory by describing blood and bone marrow analysis as well as the method of histological sectioning and immunohistochemistry in combination with various stainings that can help to understand the complex interaction between leukemic cells, their normal hematopoietic counterparts, and the bone marrow microenvironment. We conclude with describing how to image the bone marrow niche using in vivo microscopy. PMID:27581139

  2. 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

  3. Immunoglobulin D Multiple Myeloma, Plasma Cell Leukemia and Chronic Myelogenous Leukemia in a Single Patient Treated Simultaneously with Lenalidomide, Bortezomib, Dexamethasone and Imatinib

    OpenAIRE

    Naveed Ali; Pickens, Peter V.; Auerbach, Herbert E.

    2016-01-01

    Multiple myeloma (MM) is a neoplastic lymphoproliferative disorder characterized by uncontrolled monoclonal plasma cell proliferation. Among different isotypes of MM, immunoglobulin D (IgD) MM is very rare, representing only 1 to 2% of all isotypes. Chronic myelogenous leukemia (CML) is a neoplastic myeloproliferative disorder of pluripotent hematopoietic stem cell, which is characterized by the uncontrolled proliferation of myeloid cells. An 88-year-old male was diagnosed simultaneously with...

  4. Physiological measurements corroborate symptomatic improvement after therapeutic leukapheresis in a pregnant woman with chronic myelogenous leukemia.

    Science.gov (United States)

    Galera, Pallavi; Haynes, Stefanie; Sulmasy, Paula; Bailey, Jeffrey A; Greene, Mindy; Vauthrin, Michelle; Brettler, Doreen; Liebmann, James; Mark Madison, J; Weinstein, Robert

    2016-08-01

    Therapeutic leukapheresis can control the white blood cell count (WBC) of pregnant women with chronic myelogenous leukemia (CML) who have hyperleukocytosis without leukostasis. The medical justification for this treatment has not been objectively documented. We report a 27-year-old woman, diagnosed with CML at 10-week gestation, who developed severe dyspnea on exertion. A workup that included chest CT and echocardiography with a bubble study detected no cardiopulmonary pathology to explain her symptoms, and thus she was referred for leukapheresis. Prior to her first leukapheresis, which lowered her WBC from 154 × 10(3) /μL to 133 × 10(3) /μL, her oxygen saturation (SpO2 ) on room air decreased from 98 to 93% during 100 feet of slow ambulation and she was dyspneic. Just after the leukapheresis, her dyspnea on exertion was much improved and her SpO2 remained at 98% with repeat ambulation. Spirometry and lung volume studies obtained before and after her first leukapheresis demonstrated 32 and 31% improvements in forced vital capacity and forced expiratory volume in 1 s respectively, a 25% increase in functional residual capacity, and a 142% improvement in expiratory reserve volume. Residual volume decreased by almost 20%. Three times in a week, leukapheresis was continued until her WBC was controlled with interferon α-2b approximately 4 weeks later. Her dyspnea had completely resolved. She gave birth by elective caesarean section to a healthy boy at 32 weeks. Corroboration of symptom relief by leukapheresis with physiological data may justify such treatment in pregnant patients with CML. J. Clin. Apheresis 31:393-397, 2016. © 2015 Wiley Periodicals, Inc. PMID:26053950

  5. Clonal evolution in Ph{prime}-positive chronic myelogenous leukemia in blast crisis

    Energy Technology Data Exchange (ETDEWEB)

    Lin, J.H.; Gebre, W.; Kalavar, M. [Nassau City Medical Center, E. Meadow, NY (United States)]|[State Univ. of New York, Stony Brook, New York (United States)] [and others

    1994-09-01

    Chronic myelogenous leukemia (CML) usually transforms into accelerated and/or blastic phases (ABP) in 2 to 6 years, and patients with CML often succumb to the disease with cytogenetic evolvement. This 43-year-old man was know for his CML for the last 6 years. He experienced clinical deterioration with massive splenomegaly and granulocytic sarcoma in the enlarged axillary lymph nodes. The white blood cell count was 132.2 x 10{sup 9}/L with 14% basophils and less than 5% myeloblasts in the blood and the marrow. The peripheral blood disclosed 46,XY,t(9;22)(q34;q11)[9]/48,XY,+8,t(9;22)(q34;q11),+22q{sup -}[11]. He was treated accordingly and succumbed to the disease 6 months later. In CML, the Ph{prime}-positive finding is present in about 95% of the patients. The remaining Ph{prime}-negative ones are either bcr-positive or bcr-negative. This group may comprise heterogenous myeloid disorders and shows more often RAS gene mutations than {open_quotes}classic{close_quotes} CML. The common chromosomal abnormalities seen in ABP are an additional Ph{prime} chromosome, trisomy 8, isochrosome 17 and trisomy 19. Some 15-35% of patients in ABP show only Ph{prime} without additional mutation. Although overall survival is grim, patients with CML in ABP with additional chromosomal changes, regardless of the blastic natures, fare worse than those without. The presence of clonal evolution at the onset of ABP denotes clinical and hematologic deterioration and adversely effects patient`s survival.

  6. BCR-ABL transcript variations in chronic phase chronic myelogenous leukemia patients on imatinib first-line: Possible role of the autologous immune system.

    Science.gov (United States)

    Clapp, Geoffrey D; Lepoutre, Thomas; Nicolini, Franck E; Levy, Doron

    2016-05-01

    Many chronic myelogenous leukemia (CML) patients in chronic phase who respond well to imatinib therapy show fluctuations in their leukemic loads in the long-term. We developed a mathematical model of CML that incorporates the intervention of an autologous immune response. Our results suggest that the patient's immune system plays a crucial role in imatinib therapy in maintaining disease control over time. The observed BCR-ABL/ABL oscillations in such patients provide a signature of the autologous immune response. PMID:27467931

  7. Revealing stiffening and brittling of chronic myelogenous leukemia hematopoietic primary cells through their temporal response to shear stress

    Science.gov (United States)

    Laperrousaz, B.; Berguiga, L.; Nicolini, F. E.; Martinez-Torres, C.; Arneodo, A.; Maguer Satta, V.; Argoul, F.

    2016-06-01

    Cancer cell transformation is often accompanied by a modification of their viscoelastic properties. When capturing the stress-to-strain response of primary chronic myelogenous leukemia (CML) cells, from two data sets of CD34+ hematopoietic cells isolated from healthy and leukemic bone marrows, we show that the mean shear relaxation modulus increases upon cancer transformation. This stiffening of the cells comes along with local rupture events, detected as reinforced sharp local maxima of this modulus, suggesting that these cancer cells respond to a local mechanical stress by a cascade of local brittle failure events.

  8. An analysis of strategic treatment interruptions during imatinib treatment of chronic myelogenous leukemia with imatinib-resistant mutations.

    Science.gov (United States)

    Paquin, Dana; Sacco, David; Shamshoian, John

    2015-04-01

    Chronic myelogenous leukemia (CML) is a cancer of the white blood cells that results from increased and uncontrolled growth of myeloid cells in the bone marrow and the accumulation of these cells in the blood. The most common form of treatment for CML is imatinib, a tyrosine kinase inhibitor. Although imatinib is an effective treatment for CML and most patients treated with imatinib do attain some form of remission, imatinib does not completely eradicate all leukemia cells, and if treatment is stopped, all patients eventually relapse (Cortes, 2005). In Kim (2008), the authors developed a mathematical model for the dynamics of CML under imatinib treatment that incorporates the anti-leukemia immune response, and in Paquin (2011), the authors used this mathematical model to study strategic treatment interruptions as a potential therapeutic strategy for CML patients. Although the authors presented the results of several numerical simulations in Paquin (2011), the studies in that work did not include the possibility of imatinib-resistant mutations or an initial population of imatinib-resistant leukemia cells. As resistance is a significant consideration in any drug treatment, it is important to study the efficacy of the strategic treatment interruption plan in the presence of imatinib resistance. In this work, we modify the delay differential equations model of Kim (2008), Paquin (2011) to include the possibility of imatinib resistance, and we analyze strategic treatment interruptions as a potential therapeutic tool in the case of patients with imatinib-resistance leukemia cells.

  9. Clinical advances in the management of chronic myelogenous leukemia: focus on bosutinib and patient considerations

    Directory of Open Access Journals (Sweden)

    Sweet K

    2014-07-01

    Full Text Available Kendra Sweet,1 Javier Pinilla-Ibarz,1 Ling Zhang21Malignant Hematology, 2Hematopathology, H Lee Moffitt Cancer Center, Tampa, FL, USAAbstract: The treatment for chronic myeloid leukemia has changed significantly over the past 15 years, and as of now, there are five BCR-ABL1 (breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 tyrosine kinase inhibitors that have gained approval for treatment of this disease. All five are very effective drugs, and the decision surrounding which to use in specific patients is based on numerous factors. Bosutinib is one of the newer tyrosine kinase inhibitors to gain approval, and has been studied in the first-line setting as well as after failure of other tyrosine kinase inhibitors. It is an SRC-ABL1 (steroid receptor co-activator-ABL1 inhibitor that works in the presence of most kinase domain mutations. The primary side effects of bosutinib are gastrointestinal upsets. In the appropriate clinical setting, bosutinib can be considered a valuable addition to the armamentarium of treatments available for chronic myeloid leukemia.Keywords: chronic myeloid leukemia, bosutinib, treatment options

  10. Immunoglobulin D multiple myeloma, plasma cell leukemia and chronic myelogenous leukemia in a single patient treated simultaneously with lenalidomide, bortezomib, dexamethasone and imatinib

    Directory of Open Access Journals (Sweden)

    Naveed Ali

    2016-03-01

    Full Text Available Multiple myeloma (MM is a neoplastic lymphoproliferative disorder characterized by uncontrolled monoclonal plasma cell proliferation. Among different isotypes of MM, immunoglobulin D (IgD MM is very rare, representing only 1 to 2% of all isotypes. Chronic myelogenous leukemia (CML is a neoplastic myeloproliferative disorder of pluripotent hematopoietic stem cell, which is characterized by the uncontrolled proliferation of myeloid cells. An 88-year-old male was diagnosed simultaneously with IgD kappa MM and CML. A distinctive feature in this patient was the progression to plasma cell leukemia without any symptomatic myeloma stage. He was treated simultaneously with lenalidomide, bortezomib and imatinib. Synchronous occurrence of these rare hematological malignancies in a single patient is an exceedingly rare event. Multiple hypotheses to explain co-occurrence of CML and MM have been proposed; however, the exact etiological molecular pathophysiology remains elusive.

  11. Treatment of marrow stroma with interferon-alpha restores normal beta 1 integrin-dependent adhesion of chronic myelogenous leukemia hematopoietic progenitors. Role of MIP-1 alpha.

    OpenAIRE

    R Bhatia; McGlave, P B; Verfaillie, C M

    1995-01-01

    The mechanisms by which interferon-alpha (IFN-alpha) restores normal hematopoiesis in chronic myelogenous leukemia (CML) are not well understood. We have recently demonstrated that IFN-alpha acts directly on CML hematopoietic progenitors to restore their adhesion to marrow stroma by modulating beta 1 integrin receptor function. In the present study we examined the effect of IFN-alpha treatment of marrow stroma on subsequent adhesion of CML progenitors. Stromal layers were preincubated with IF...

  12. Curcumin inhibits in vitro and in vivo chronic myelogenous leukemia cells growth: a possible role for exosomal disposal of miR-21

    OpenAIRE

    Taverna, S; Giallombardo, M.; Pucci, M; Flugy, A; Manno, M.; Raccosta, S; Rolfo, C.; Leo, G.; Alessandro, R

    2015-01-01

    Exosomes are nanosize vesicles released from cancer cells containing microRNAs that can influence gene expression in target cells. Curcumin has been shown to exhibit antitumor activities in a wide spectrum of human cancer. The addition of Curcumin, to Chronic Myelogenous Leukemia (CML) cells, caused a dose-dependent increase of PTEN, target of miR-21. Curcumin treatment also decreased AKT phosphorylation and VEGF expression and release. Colony formation assays indicated that Curcumin affects ...

  13. Isorhamnetin 3-O-robinobioside from Nitraria retusa leaves enhance antioxidant and antigenotoxic activity in human chronic myelogenous leukemia cell line K562

    Directory of Open Access Journals (Sweden)

    Boubaker Jihed

    2012-08-01

    Full Text Available Abstract Background In this report, the isorhamnetin 3-o-robinobioside and its original extract, the ethyl acetate extract, from Nitraria retusa leaves, were evaluated for their ability to induce antioxidant and antigenotoxic effects in human chronic myelogenous leukemia cell line. Methods Nitraria retusa products properties were carried out by firstly evaluating their effects against lipid peroxidation induced by H2O2, using the thiobarbituric acid reactive substances species (TBARS assay, and proceeding to the assay of cellular antioxidant activity, then doing the comet assay. Results The isorhamnetin 3-o-robinobioside showed a protective effect against lipid peroxidation induced by H2O2. The same natural compound and ethyl acetate extract inhibited oxidation induced by 2,2′-azobis (2-amidinopropane dihydrochloride in human chronic myelogenous leukemia cells with respectively 50% inhibitory concentration values of 0.225 mg/ml and 0.31 mg/ml, reflecting a significant antioxidant potential. The same two products inhibited the genotoxicity induced by hydroxyl radicals in the same human cell line (by 77.77% at a concentration of 800 μg/ml and by 80.55% at a concentration of 1000 μg/ml respectively. Conclusions The isorhamnetin 3- o-robinobioside and its original extract, the ethyl acetate extract, from Nitraria retusa leaves, have a great antioxidant and antigenotoxic potential on human chronic myelogenous leukemia cell line K562.

  14. Immunological effects of donor lymphocyte infusion in patients with chronic myelogenous leukemia relapsing after bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Castro F.A.

    2004-01-01

    Full Text Available Allogeneic bone marrow transplantation (alloBMT is the only curative therapy for chronic myelogenous leukemia (CML. This success is explained by the delivery of high doses of antineoplastic agents followed by the rescue of marrow function and the induction of graft-versus-leukemia reaction mediated by allogeneic lymphocytes against host tumor cells. This reaction can also be induced by donor lymphocyte infusion (DLI producing remission in most patients with CML who relapse after alloBMT. The immunological mechanisms involved in DLI therapy are poorly understood. We studied five CML patients in the chronic phase, who received DLI after relapsing from an HLA-identical BMT. Using flow cytometry we evaluated cellular activation and apoptosis, NK cytotoxicity, lymphocytes producing cytokines (IL-2, IL-4 and IFN-gamma, and unstimulated (in vivo lymphocyte proliferation. In three CML patients who achieved hematological and/or cytogenetic remission after DLI we observed an increase of the percent of activation markers on T and NK cells (CD3/DR, CD3/CD25 and CD56/DR, of lymphocytes producing IL-2 and IFN-gamma, of NK activity, and of in vivo lymphocyte proliferation. These changes were not observed consistently in two of the five patients who did not achieve complete remission with DLI. The percent of apoptotic markers (Fas, FasL and Bcl-2 on lymphocytes and CD34-positive cells did not change after DLI throughout the different study periods. Taken together, these preliminary results suggest that the therapeutic effect of DLI in the chronic phase of CML is mediated by classic cytotoxic and proliferative events involving T and NK cells but not by the Fas pathway of apoptosis.

  15. Quantification of BCR-ABL mRNA in Plasma/Serum of Patients with Chronic Myelogenous Leukemia

    Directory of Open Access Journals (Sweden)

    Miwako Narita, Anri Saito, Aya Kojima, Minami Iwabuchi, Naoya Satoh, Takayoshi Uchiyama, Akie Yamahira, Tatsuo Furukawa, Hirohito Sone, Masuhiro Takahashi

    2012-01-01

    Full Text Available Quantification of tumor-associated mRNA extracted from blood cells/tissues containing tumor cells is used for evaluation of treatment efficacy or residual tumor cell burden in tumors including leukemia. However, this method using tumor cell-containing blood/tissue is difficult to evaluate the whole tumor cell burden in the body. In order to establish an efficient method to evaluate the whole tumor cell burden in the body, we tried to quantify tumor-associated mRNA existing in plasma/serum instead of leukemia cell-containing blood cells in patients with chronic myelogenous leukemia (CML and compared the levels of BCR-ABL mRNA between plasma/serum and peripheral blood cells. mRNA of BCR-ABL, WT1 or GAPDH (control molecule was detected by real-time RT-PCR using RNA extracted from plasma/serum of almost all the patients with CML. Copy numbers of BCR-ABL mRNA were significantly correlated between plasma/serum and peripheral blood cells. However, levels of BCR-ABL mRNA extracted from serum were low compared with those extracted with peripheral blood cells. The present findings suggest that although real-time RT-PCR of mRNA existing in plasma/serum could be used for evaluating the whole tumor cell burden in the body, it's required to establish an efficient method to quantify plasma/serum mRNA by nature without degrading during the procedure.

  16. The BCR-ABLT315I mutation compromises survival in chronic phase chronic myelogenous leukemia patients resistant to tyrosine kinase inhibitors, in a matched pair analysis

    DEFF Research Database (Denmark)

    Nicolini, Franck E; Ibrahim, Amr R; Soverini, Simona;

    2013-01-01

    patients with chronic phase chronic myelogenous leukemia harboring a T315I mutation and resistant to imatinib mesylate was compared to a similar cohort of 53 chronic phase patients resistant to imatinib, but with no detectable T315I mutation, in the pre-ponatinib era. These patients were matched according...... to age at diagnosis, interval between disease diagnosis and start of imatinib treatment, and duration of imatinib therapy. Kaplan-Meier survival analyses demonstrated the significant negative impact of the presence of the T315I mutation on overall survival (since imatinib-resistance: 48.4 months for...... T315I(+) patients versus not reached for T315I(-) ones; P=0.006) and failure-free survival (since imatinib-resistance: 34.7 months for T315I(+) patients versus not reached for T315I(-) patients; P=0.003). In addition, Cox proportional hazard models adjusted on overall survival demonstrated the...

  17. Chronic Myelogenous Leukemia Cells Contribute to the Stromal Myofibroblasts in Leukemic NOD/SCID Mouse In Vivo

    Directory of Open Access Journals (Sweden)

    Ryosuke Shirasaki

    2012-01-01

    Full Text Available We recently reported that chronic myelogenous leukemia (CML cells converted into myofibroblasts to create a microenvironment for proliferation of CML cells in vitro. To analyze a biological contribution of CML-derived myofibroblasts in vivo, we observed the characters of leukemic nonobese diabetes/severe combined immunodeficiency (NOD/SCID mouse. Bone marrow nonadherent mononuclear cells as well as human CD45-positive cells obtained from CML patients were injected to the irradiated NOD/SCID mice. When the chimeric BCR-ABL transcript was demonstrated in blood, human CML cells were detected in NOD/SCID murine bone marrow. And CML-derived myofibroblasts composed with the bone marrow-stroma, which produced significant amounts of human vascular endothelial growth factor A. When the parental CML cells were cultured with myofibroblasts separated from CML cell-engrafted NOD/SCID murine bone marrow, CML cells proliferated significantly. These observations indicate that CML cells make an adequate microenvironment for their own proliferation in vivo.

  18. Coexistent chronic myelogenous leukemia with squamous cell carcinoma of the larynx associated with NOD2/CARD15 mutation in a young adult.

    Science.gov (United States)

    Fraczek, Marcin; Stembalska, Agnieszka; Karpinski, Pawel; Krecicki, Tomasz

    2016-06-01

    We report the case of a 37-year-old man with human papillomavirus-positive squamous cell carcinoma of the larynx coexisting with chronic myelogenous leukemia. The patient had no history of smoking or alcohol consumption. Within a few months, his rapidly growing tumor was classified as T4aN2cM0. It could be assumed that the rapid increase in the tumor mass, which did not respond positively to treatment, might have been associated with the coexistence of the chronic myelogenous leukemia, which had been found incidentally. Genetic testing revealed the presence of insertion mutation 3020insC within the NOD2 gene, which might be an important genetic predisposing factor, not only for a single tumor such as laryngeal cancer, but also for multiple primary neoplasms. The presence of an NOD2 mutation could significantly worsen the course of the cancer. Therefore, given the relatively high frequency of 3020insC mutations in the general population, it might be reasonable to perform genetic testing on a wider scale for patients with head or neck cancer, particularly in cases that follow an atypical course. It is also worth emphasizing the importance of thorough and periodically repeated laryngeal examinations in patients with chronic leukemia. PMID:27304445

  19. Curcumin synergistically augments bcr/abl phosphorethieate antisense oligonucleotides to inhibit growth of chronic myelogenous leukemia cells

    Institute of Scientific and Technical Information of China (English)

    Kun-zhong ZHANG; Jian-hua XU; Xiu-wang HUANG; Li-xian WU; Yu SU; Yuan-zhong CHEN

    2007-01-01

    Aim: To investigate the growth inhibition effect of the combination of bcr/abl phosphorothioate antisense oligonucleotides (PS-ASODN) and curcumin (cur), and the possible mechanisms of cur on the chronic myelogenous leukemia cell line K562. Methods: The K562 cell line was used as a P210bcr/abl-positive cell model in vitro and was exposed to different concentrations of PS-ASODN (0-20 μmol/L), cur (0-20 μmol/L), or a combination of both. Growth inhibition and apoptosis of K562 cells were assessed by MTT assay and AO/EB fluorescent staining, respec-tively. The expression levels of P210bct/abl, NF-κB and heat shock protein 90 (Hsp90) were assessed by Western blot. Results: Exposure to cur (5-20 μmol/L) and PS-ASODN (5-20 μmol/L) resulted in a synergistic inhibitory effect on cell growth.Growth inhibition was associated with the inhibition of the proliferation and in-duction of apoptosis. Western blot analysis showed that the drugs synergisti-cally downregulated the level of P210bcr/abl and NF-κB. Cur downregulated Hsp90,whereas no synergism was observed when cur was combined with PS-ASODN.Conclusion: PS-ASODN and cur exhibited a synergistic inhibitory effect on the cell growth of K562. The synergistic growth inhibition was mediated through different mechanisms that involved the inhibition of P210bcr/abl.

  20. Cytarabine added to interferon improves the cost-effectiveness of initial therapy for patients with early chronic phase chronic myelogenous leukemia.

    Science.gov (United States)

    Beck, J R; Guilhot, J; Giles, F J; Aoki, N; Wirt, D P; Guilhot, F

    2001-03-01

    The French Chronic Myeloid Leukemia Study Group prospective randomized study results indicate that the addition of cytarabine to alpha interferon (IFN-alpha) increases the rate of major cytogenetic response and prolongs survival in patients with early chronic phase chronic myelogenous leukemia (CML). The French group study design permitted a single crossover to include or discontinue cytarabine or interferon. Endpoints were overall survival, complete hematologic remission (CHR) at six months, and major cytogenetic response at 12 months. We modified a published Markov model that compared IFN-alpha alone to IFN-alpha plus cytarabine and included the possibility of crossover as in the French study. The model permits allogeneic and autologous stem cell transplantation (SCT), and follows cytogenetic response and acceleration of CML through death. Treatment response, toxicity, and survival are drawn from the French Chronic Myeloid Leukemia Study Group population of 810 patients on an intention-to-treat model. Survivals are extended to 62 months based on currently available follow-up. Costs from a United States oncology specialty institution, and state utilities from previous research and a quality-adjusted Time Without Symptoms or Toxicity analysis of the subject study were discounted at 3% per annum. At the median cohort age of 50, cytarabine offers 21 months of added median survival to IFN-alpha, which itself is superior to conventional chemotherapy by 21 months. Cost-effectiveness estimates for cytarabine added to IFN-alpha range from $7,000 per quality-adjusted life year (QALY) to $35,000 per QALY, under all plausible assumptions superior to IFN-alpha alone. The model is sensitive to the quality of life on therapy, as well as to remission rate with additive cytarabine, although the cost-effectiveness calculations are robust over the entire range of clinical assumptions. Based on data from the French study, cytarabine added to IFN-alpha substantially improves the cost

  1. Splenic hemochromatosis incidentally found on Tc-99m MDP bone scan in a chronic myelogenous leukemia patient who received bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Byeong Cheol; Seo, Ji Hyoung; Bae, Jin Ho; Jeong, Sin Young; Lee, Jae Tae; Lee, Kyu Bo [School of Medicine, Kyungpook National Univ., Daegu (Korea, Republic of)

    2004-02-01

    Tc-99m MDP bone scan was performed to evaluate a generalized bone pain in a 24-year-old male chronic myelogenous leukemia patient who received bone marrow transplantation at 7 months ago. The patient had received large amounts of blood transfusion for managing symptoms related to anemia. Bone scan revealed substantial splenic tracer uptake. Magnetic resonance image and laboratory evidence of hemochromatosis suggests that the presence of large quantities of iron in the spleen of this patient may have been responsible for the splenic uptake of the bone scanning agent. The authors report a c ase of splenic hemochromatosis incidentally found on Tc-99m MDP bone scan.

  2. An Adult Male Presenting with Concurrent Plasma Cell Myeloma Involving a CCND1-IGH Translocation and Chronic Myelogenous Leukemia with a Variant (9;22) Translocation.

    Science.gov (United States)

    Lee, Peter M; Siangchin, Ken; Song, Sophie; Shabsovich, David; Naeini, Yalda; Tirado, Carlos A

    2016-01-01

    The t(11;14)(q13;q32) involving IGH and CCND1 a nd t(9;22) (q34;q11.2) involving BCR and ABL1 are common abnormalities in plasma cell myeloma (PCM) and chronic myelogenous leukemia (CML), respectively. However, the concurrence of the two malignancies is extremely rare. Herein, we present a case of an 87-year-old male who presented with anemia and monocytosis. FISH studies on a bone marrow sample enriched for plasma cells detected a t(11;14) positive for IGH and CCND1 fusion in 92% of nuclei. However, cytogenetic analysis of the bone marrow revealed a t(9;22)(q34;q11.2) in 40% of the metaphases. Interphase and metaphase FISH studies on the sample confirmed the presence of the BCR-ABL1 fusion in 88% of nuclei but did not show any signals corresponding to the derivative 9, suggesting a variant t(9;22) with a deletion or additional material of unknown origin at the 9q34 band of the derivative 9 and a derivative 22 bearing the BCR-ABL1 fusion gene. The concurrence of plasma cell myeloma and chronic myelogenous leukemia is extremely rare with less than 20 cases reported. The molecular pathway in which the multiple malignancies arise is still poorly understood, and this case provides insight into the concurrence of PCM and CML. PMID:27584682

  3. Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.

    Science.gov (United States)

    2016-10-07

    Leukemia; Leukemia,Pediatric; Leukemia, Myleiod; Leukemia, Mylegenous, Chronic; Leukemia, Mylegenous, Accelerated; BCR-ABL Positive; Myeloproliferative Disorder; Bone Marrow Disease; Hematologic Diseases; Neoplastic Processes; Imatinib; Dasatinib; Enzyme Inhibitor; Protein Kinase Inhibitor

  4. BCR/ABL-negative primitive progenitors suitable for transplantation can be selected from the marrow of most early-chronic phase but not accelerated-phase chronic myelogenous leukemia patients

    OpenAIRE

    Verfaillie, Catherine; R Bhatia; Miller, W.; F. Mortari; Van Roy, V.; Burger, S.; Mccullough, J; Stieglbauer, K; Dewald, G; Heimfeld, S; Miller, J. S.; McGlave, P B

    1996-01-01

    We have previously reported that selection of marrow cells on the basis of the CD34+HLA-DR- phenotype (34+DR-) may result in the recovery of Philadelphia chromosome (Ph)- and BCR/ABL-negative long-term culture-initiating cells (LTC-IC) in selected patients with chronic myelogenous leukemia (CML). We now present data on 27 early chronic-phase ([ECP] studied within 1 year after diagnosis) and 23 advanced-phase ([AP] late chronic phase, ie, studied >1 year from diagnosis, or accelerated phase) C...

  5. Cessation of tyrosine kinase inhibitors in patients with chronic-phase chronic myelogenous leukemia following durable complete molecular response: a single center facing the dilemma.

    Science.gov (United States)

    Iliakis, Theodoros; Papadopoulou, Vasiliki; Diamantopoulos, Panagiotis T; Panayiotidis, Panayiotis; Zervakis, Konstantinos; Giannakopoulou, Nefeli; Tilimidos, Gerassimos; Angelopoulou, Maria; Siakantaris, Marina P; Pangalis, Gerassimos; Mantzourani, Marina; Variami, Eleni; Viniou, Nora Athina

    2013-08-01

    Tyrosine kinase inhibitors (TKIs), namely imatinib mesylate (IM) and recently approved second-generation TKIs dasatinib and nilotinib, are currently considered the treatment of choice for newly-diagnosed chronic phase chronic myelogenous leukemia (CP-CML). Although treatment with TKIs has not yet been proven curative, it certainly accomplishes a sustained control of the disease in the vast majority of patients. More than a decade after the successful launching of IM in first-line treatment of CP-CML and the subsequent introduction of second-generation TKIs in this setting, the question of the possibility of TKI cessation in a specific subset of patients has emerged. Side-effects of TKIs, along with some patients' wish to abandon the drugs and the rising financial burden upon healthcare systems, have led to the dilemma whether IM can be safely withdrawn after achieving deep molecular remissions and which patients are suitable for this discontinuation. We examined the data of our patients with CML in search of potential canditates for cessation of TKI therapy and identified their characteristics. We also performed a thorough review of the relevant literature. Eight out of fifty patients were discriminated on grounds of sustained complete molecular response (CMR) exceeding 12 months, most of them with a low or intermediate Sokal score at diagnosis. The median interval from IM initiation to CMR was almost 2 years and the median duration of detected CMR reached 6.5 years. Based on the promising results of prospective clinical trials reporting successful cessation of treatment with TKIs on selected subgroups of patients, we decided to proceed to interruption of therapy in the specific subset of our patients and closely monitor their response. PMID:23898127

  6. Skin changes in acute myelogenous leukemia

    Directory of Open Access Journals (Sweden)

    Mittal R

    2000-01-01

    Full Text Available A 65-year old woman developed progressive, firm, mild to moderately itchy, erythematous, papular and nodular lesions, over cheeks, extensors of limbs, scalp and lower back without any accompanying systemic complaints except for severe backache. Initially clinical diagnosis was cutaneous sarcoidosis. However presence of myeloblasts, monoblasts, myelocytes and metamyelocytes in peripheral blood smear and typical histopathology of nodule with mixed cellular infiltrate more around blood vessels, sweat glands and hair follicles with admixture of larger polymorphonuclears (myeloblasts/myelocytes, eosinophils with double nuclei, and larger phagocytic cells confirmed the diagnosis of acute myelogenous leukemia (AML.

  7. ALLOGENEIC PERIPHERAL BLOOD AND BONE MARROW STEM CELL TRANSPLANTATION FOR CHRONIC MYELOGENOUS LEUKEMIA: A SINGLE CENTER STUDY

    Directory of Open Access Journals (Sweden)

    A. Ghavamzadeh

    2003-08-01

    Full Text Available In this center, from 1991 to 2002, 89 chronic myelogenous leukemic (CML patients, age ranging between 8-48 years with a median age of 29, underwent hematopoietic stem cell transplantation. Eighty-eight patients were in the first chronic phase of disease. Twenty-three patients received bone marrow transplantation (BMT and 66 patients received peripheral blood stem cell transplantations (PBSCT. Transplantation was performed at a median interval of 19 months post-diagnosis. All with five exceptions received busulfan + cyclophosphamide (Bu Cy conditioning regimens. To maintain graft vs. host disease (GVHD prophylaxis, all with three exceptions received cyclosporine + metothrexate. Administration of granulocyte colony stimulating factor (G-CSF, per protocol, was included in post-transplantation regimens from the year 1999 on 48 patients. All patients received marrow transplantations from sibling donors. Fifty seven of transplanted patients are alive. Disease free survivals (DFS from 6.2 to 9.5 and from 2.2 to 6.2 years for BMT group were 38.2% and 47.8%, respectively. DFS for PBSCT group was calculated as 54.3% in a period of 1.9 to 4.6 years.

  8. Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias

    Science.gov (United States)

    2010-09-21

    Myelodysplastic Syndrome; Acute Myeloid Leukemia; Myeloproliferative Disorders; Acute Lymphocytic Leukemia; Acute Promyelocytic Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Myelofibrosis; Chronic Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia

  9. Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia

    Directory of Open Access Journals (Sweden)

    Judith E Karp

    2008-09-01

    Full Text Available Judith E Karp1, Jeffrey E Lancet21Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA; 2H. Lee Moffitt Comprehensive Cancer Center, Tampa, Florida, USAAbstract: Farnesyltransferase inhibitors (FTIs represent a new class of signal transduction inhibitors that block the processing of cellular polypeptides that have cysteine terminal residues and, by so doing, interdict multiple pathways involved in proliferation and survival of diverse malignant cell types. Tipifarnib is an orally bioavailable, nonpeptidomimetic methylquinolone FTI that has exhibited clinical activity in patients with myeloid malignancies including elderly adults with acute myelogenous leukemia (AML who are not candidates for traditional cytotoxic chemotherapy, patients with high-risk myelodysplasia, myeloproliferative disorders, and imatinib-resistant chronic myelogenous leukemia. Because of its relatively low toxicity profile, tipifarnib provides an important alternative to traditional cytotoxic approaches for elderly patients who are not likely to tolerate or even benefit from aggressive chemotherapy. In this review, we will focus on the clinical development of tipifarnib for treatment of newly diagnosed AML, both as induction therapy for elderly adults with poor-risk AML and as maintenance therapy following achievement of first complete remission following induction and consolidation therapies for poor-risk AML. As with all other malignancies, the optimal approach is likely to lie in rational combinations of tipifarnib with cytotoxic, biologic and/or immunomodulatory agents with non-cross-resistant mechanisms of action. Gene expression profi ling has identified networks of differentially expressed genes and gene combinations capable of predicting response to single agent tipifarnib. The clinical and correlative laboratory trials in progress and under development will provide the critical foundations for

  10. Functionally deregulated AML1/RUNX1 cooperates with BCR-ABL to induce a blastic phase-like phenotype of chronic myelogenous leukemia in mice.

    Directory of Open Access Journals (Sweden)

    Kiyoko Yamamoto

    Full Text Available Patients in the chronic phase (CP of chronic myelogenous leukemia (CML have been treated successfully following the advent of ABL kinase inhibitors, but once they progress to the blast crisis (BC phase the prognosis becomes dismal. Although mechanisms underlying the progression are largely unknown, recent studies revealed the presence of alterations of key molecules for hematopoiesis, such as AML1/RUNX1. Our analysis of 13 BC cases revealed that three cases had AML1 mutations and the transcript levels of wild-type (wt. AML1 were elevated in BC compared with CP. Functional analysis of representative AML1 mutants using mouse hematopoietic cells revealed the possible contribution of some, but not all, mutants for the BC-phenotype. Specifically, K83Q and R139G, but neither R80C nor D171N mutants, conferred upon BCR-ABL-expressing cells a growth advantage over BCR-ABL-alone control cells in cytokine-free culture, and the cells thus grown killed mice upon intravenous transfer. Unexpectedly, wt.AML1 behaved similarly to K83Q and R139G mutants. In a bone marrow transplantation assay, K83Q and wt.AML1s induced the emergence of blast-like cells. The overall findings suggest the roles of altered functions of AML1 imposed by some, but not all, mutants, and the elevated expression of wt.AML1 for the disease progression of CML.

  11. RalA, a GTPase targeted by miR-181a, promotes transformation and progression by activating the Ras-related signaling pathway in chronic myelogenous leukemia

    Science.gov (United States)

    Luo, Xiaochuang; Yang, Juhua; Li, Yumin; Li, Tianfu; Wang, Ruirui; Fei, Jia

    2016-01-01

    BCR/ABL is a well-known activator of multiple signaling pathways. RalA, a Ras downstream signaling molecule and a small GTPase, plays an important role in Bcr-Abl-induced leukemogenesis but the exact mechanism remains elusive. Here, we show that RalA GTPase activity is commonly high in chronic myelogenous leukemia (CML) cell lines and patient samples. Overexpression of RalA results in malignant transformation and progression, and induces resistance to imatinib (IM) in BaF3 and K562 cell lines. RalA reduced survival and led to IM resistance in a xenografted mouse model. Ablation of RalA by either siRNA or miR-181a, a RalA targeting microRNA, attenuated the malignant phenotypes in K562 cells. RBC8, a selective Ral inhibitor, enhanced the inhibitory effects of IM in K562, KCL22 and BaF3-P210 cells. Interestingly, the phospho-specific protein microarray assay revealed that multiple phosphorylation signal proteins were decreased by RalA inhibition, including SAPK, JNK, SRC, VEGFR2, P38 MAPK, c-Kit, JunB, and Keratin18. Among them, P38 MAPK and SAPK/JNK are Ras downstream signaling kinases. Taken together, RalA GTPase might be an important oncogene activating the Ras-related signaling pathway in CML. PMID:26967392

  12. Isolated Ocular Manifestation of Relapsed Chronic Myelogenous Leukemia Presenting as Myeloid Blast Crisis in a Patient on Imatinib Therapy: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Rohit Gulati

    2015-01-01

    Full Text Available Blast phase in chronic myelogenous leukemia (CML has rarely been reported to involve extramedullary sites like skin, lymph nodes, and central nervous system. Clinical history, characteristic hematologic findings (elevated leukocyte counts, myelocytic predominance, and basophilia, and Philadelphia chromosome are of high diagnostic significance especially in isolated extramedullary presentations. We describe a unique case of CML relapse with blast phase involving the eye. A 66-year-old man with a known diagnosis of CML on imatinib and in molecular remission for 3 years presented with a painful blind eye. Histologic examination revealed diffuse involvement of choroid, iris, vitreous humor, and the optic nerve by blast cells. The blasts expressed CD34, aberrant TdT, and a myeloid phenotype (CD13, CD33, and CD117. Fluorescence in situ hybridization (FISH of vitreous fluid detected BCR-ABL1 gene rearrangement. Additionally, trisomy 8 and gains of 9 and 22 were seen which were not present in the initial diagnostic marrow study 3 years ago. At relapse, the bone marrow, peripheral blood, and the cerebrospinal fluid were not involved by CML. Patient received induction chemotherapy and single dose prophylactic intrathecal methotrexate and was maintained on antityrosine kinase therapy and eventually underwent allogenic stem cell transplantation.

  13. Induction of apoptosis by shikonin through a ROS/JNKmediated process in Bcr/Abl-positive chronic myelogenous leukemia (CML) cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This study examined the signaling events induced by shikonin that lead to the induction of apoptosis in Bcr/ Abl-positive chronic myelogenous leukemia (CML) cells (e.g., K562, LAMA84). Treatment of K562 cells with shikonin (e.g., 0.5 μM) resulted in profound induction of apoptosis accompanied by rapid generation of reactive oxygen species (ROS), striking activation of c-Jun-N-terminai kinase (JNK) and p38, marked release of the mitochondrial proteins cytochrome c and Smac/DIABLO, activation of caspase-9 and -3, and cleavage of PARP. Scavenging of ROS completely blocked all of the above-mentioned events (i.e., JNK and p38 phosphorylation, cytochrome c and Smac/DIABLO release, caspase and PARP cleavage, as well as the induction of apoptosis) following shikonin treatment. Inhibition of JNK and knock-down of JNKI significantly attenuated cytochrome c release, caspase cleavage and apoptosis, but did not affect shikonin-mediated ROS production. Additionally, inhibition of caspase activation completely blocked shikonin-induced apoptosis, but did not appreciably modify shikonin-mediated cytochrome c release or ROS generation. Altogether, these findings demonstrate that shikonin-induced oxidative injury operates at a proximal point in apoptotic signaling cascades, and subsequently activates the stress-related JNK pathway, triggers mitochondrial dysfunction, cytochrome c release, and caspase activation, and leads to apoptosis. Our data also suggest that shikonin may be a promising agent for the treatment of CML, as a generator of ROS.

  14. Safranal, a Crocus sativus L constituent suppresses the growth of K-562 cells of chronic myelogenous leukemia. In silico and in vitro study.

    Science.gov (United States)

    Geromichalos, George D; Papadopoulos, Theophanis; Sahpazidou, Despina; Sinakos, Zacharias

    2014-12-01

    Crocin, a main constituent of Crocus sativus L (saffron), has been found to inhibit the growth of K-562 human chronic myelogenous leukemia (CML) cells expressing Bcr-Abl protein tyrosine kinase activity. The aim of our study is to investigate the ability of the bioactive saffron's constituents, crocin (CRC) and safranal (SFR), to inhibit the Bcr-Abl protein activity employing an in silico approach, as well as the in vitro effect of these compounds on K-562 growth and gene expression of Bcr-Abl. In silico molecular docking studies revealed that mostly SFR can be attached to Bcr-Abl protein, positioned inside the protein's binding cavity at the same place with the drug used in the treatment of CML, imatinib mesylate (IM). The predicted polar interactions and hydrophobic contacts constructing a hydrophobic cavity inside the active site, explain the observed inhibitory activity. Cytotoxicity experiments showed that SFR and CRC mediate cytotoxic response to K562 cells. In vitro studies on the expression of Bcr-Abl gene revealed that SFR and in a lesser degree IM inhibited the expression of the gene, while in contrast CRC induced an increase. The ultimate goal was to evaluate the existence of a potential antitumor activity of saffron's constituents SFR and CRC.

  15. Integrative genomic analysis in K562 chronic myelogenous leukemia cells reveals that proximal NCOR1 binding positively regulates genes that govern erythroid differentiation and Imatinib sensitivity.

    Science.gov (United States)

    Long, Mark D; van den Berg, Patrick R; Russell, James L; Singh, Prashant K; Battaglia, Sebastiano; Campbell, Moray J

    2015-09-01

    To define the functions of NCOR1 we developed an integrative analysis that combined ENCODE and NCI-60 data, followed by in vitro validation. NCOR1 and H3K9me3 ChIP-Seq, FAIRE-seq and DNA CpG methylation interactions were related to gene expression using bootstrapping approaches. Most NCOR1 combinations (24/44) were associated with significantly elevated level expression of protein coding genes and only very few combinations related to gene repression. DAVID's biological process annotation revealed that elevated gene expression was uniquely associated with acetylation and ETS binding. A matrix of gene and drug interactions built on NCI-60 data identified that Imatinib significantly targeted the NCOR1 governed transcriptome. Stable knockdown of NCOR1 in K562 cells slowed growth and significantly repressed genes associated with NCOR1 cistrome, again, with the GO terms acetylation and ETS binding, and significantly dampened sensitivity to Imatinib-induced erythroid differentiation. Mining public microarray data revealed that NCOR1-targeted genes were significantly enriched in Imatinib response gene signatures in cell lines and chronic myelogenous leukemia (CML) patients. These approaches integrated cistrome, transcriptome and drug sensitivity relationships to reveal that NCOR1 function is surprisingly most associated with elevated gene expression, and that these targets, both in CML cell lines and patients, associate with sensitivity to Imatinib.

  16. Rearrangement and expression of beta-T-cell receptor and immunoglobulin genes in established Ph1 chronic myelogenous leukemia cell lines.

    Science.gov (United States)

    Berenson, J; Koeffler, H P

    1989-01-01

    We have determined the arrangement and expression of immunoglobulin (Ig) and beta-T-cell receptor (TCR) genes in six established Philadelphia chromosome-positive (Ph1) chronic myelogenous leukemia (CML) cell lines, and correlated these results with their phenotypic characteristics. Three cell lines with nonlymphoid characteristics, EM2, EM3, and K562, did not demonstrate rearrangement or expression of Ig or beta-TCR genes. A new cell line, MB, with a mature B-cell phenotype recently established in our laboratory, contained light and heavy chain immunoglobulin gene rearrangements and expressed mature Ig RNA. In a cell line with an early lymphoid phenotype, BV173, this analysis showed rearrangement of Ig heavy chain and beta-TCR genes, unrearranged Ig light chain DNA, and expression of only an immature beta-TCR transcript. This line provides evidence for T-cell lineage involvement in Ph1 CML. One cell line without markers of any cell type, KCL-22, demonstrated rearranged, unexpressed Ig heavy chain genes, suggesting these cells are at the very earliest stages of lymphoid differentiation. These lines should provide valuable tools to dissect the molecular biology of differentiation in CML and in early lymphocytes.

  17. Establishment and Utilization of a Tetracycline-controlled Inducible RNA Interfering System to Repress Gene Expression in Chronic Myelogenous Leukemia Cells

    Institute of Scientific and Technical Information of China (English)

    Fan YANG; Yun ZHANG; Ying-Li CAO; Shu-Hui WANG; Li LIU

    2005-01-01

    RNA interference (RNAi), a posttranscriptional gene silencing process mediated by small doublestranded RNA specifically complementary to the targeted transcript, has been used extensively in the development of novel therapeutic approaches against various human diseases including chronic myelogenous leukemia (CML).Here, we report the successful construction of a tetracycline-controlled siRNA in CML cell line K562. A K562 cell line stably expressing the reverse tetracycline-controlled transactivator (rtTA) was constructed. A tetracycline responsive element (TRE) was integrated into the RNA polymerase Ⅲ promoter region of pBS/U6 that was used to drive specific siRNA to target the novel cytokine receptor-like factor 3 (CRLF3) gene. The results show that rtTA was able to recognize the TRE to prevent siRNA-mediated exogenous and endogenous CRLF3 gene repressions. Moreover, CRLF3-siRNA mediated gene repression could be induced in a dose-dependent manner in the presence of doxycycline. Thus, the inducible siRNAi system in K562 cells might be useful for the study of RNAi-mediated therapeutic approaches against CML.

  18. Perifosine induces protective autophagy and upregulation of ATG5 in human chronic myelogenous leukemia cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Yin TONG; Yan-yan LIU; Liang-shun YOU; Wen-bin QIAN

    2012-01-01

    Aim:The efficacy of the Akt inhibitor perifosine against chronic myeloid leukemia (CML)cells and its mechanisms of action are unknown.In this study,the cytotoxic effects of perifosine on CML and acute myeloid leukemia (AML)cell lines were compared to elucidate the mechanisms underlying the differences.Methods:Human AML cell lines Kasumi-1 and HL-60,and the CML cell line K562 were used.Cell viability was quantitated using MTT assay.Apoptosis was determined using Annexin V-FITC/propidium iodide and Hoechst staining,which were followed by flow cytometry and fluorescence microscopy analysis,respectively.Caspase pathway activation and the expression of autophagy-related genes were examined using Western blot.Autophagy was studied using electron microscopy,the acridine orange staining method,and GFP-LC3 was examined with fluorescence microscopy.Results:In contrast to AML cell lines,the CML cell lines K562 and K562/G (an imatinib-insensitive CML cell line)were resistant to perifosine (2.5-20 μmol/L)in respect to inhibiting cell growth and inducing apoptosis.Perifosine (2.5,5,and 10 μmol/L)inhibited Akt and its phosphorylation in AML cells,but not in CML cells.Treatment with perifosine (20 μmol/L)resulted in autophagy in CML cells as shown by the increased formation of acidic vesicular organelles and the accumulation of LC3-II.Treatment of CML cells with perifosine (5,10,and 20 μmol/L)dose-dependently upregulated AGT5,but not Beclin 1 at the protein level.Furthermore,inhibition of autophagyby chloroquine (40 nmol/L)significantly suppressed the cell growth and induced apoptosis in CML cells treated with perifosine (20 μmol/L).Conclusion:Our results show that CML cell lines were resistant to the Akt inhibitor perifosine in vitro,which is due to perifosine-induced protective autophagy and upregulation of ATG5.

  19. Imatinib induces H2AX phosphorylation and apoptosis in chronic myelogenous leukemia cells in vitro via caspase-3/Mst1 pathway

    Institute of Scientific and Technical Information of China (English)

    Yan-jun ZHANG; Lian-ning DUAN; Cheng-rong LU; Yan CAO; Yuan LUO; Rong-feng BAO; Shu YAN; Mei XUE; Feng ZHU; Zhe WANG

    2012-01-01

    Aim:Histone H2AX is a novel tumor suppressor and its phosphorylation at the C terminus (Ser139 and Tyr142)is required for tumor cell apoptosis.The aim of the present study was to elucidate the mechanisms underlying imatinib-induced C-terminal phosphorylation of H2AX in chronic myelogenous leukemia cells in vitro.Methods:BCR-ABL-positive K562 cells were used.Microscopy,Western blotting and flow cytometry were used to study the signaling pathways that regulate imatinib-induced H2AX phosphorylation and the apoptotic mechanisms.Results:Treatment of K562 cells with imatinib (1-8 μmol/L)induced phosphorylation of H2AX at Ser139 and Tyr142 in time-and dose-dependent manners.In contrast,imatinib at the same concentrations did not affect H2AX acetylation at Lys 5,and the acetylated H2AX maintained a higher level in the cells.Meanwhile,imatinib (1-8 μmol/L)activated caspase-3 and its downstream mammalian STE20-like kinase 1 (Mst1),and induced apoptosis of K562 cells.The caspase-3 inhibitor Z-VAD (40 μmol/L)reduced imatinibinduced H2AX phosphorylation at Ser139 and Tyr142 and blocked imatinib-induced apoptosis of K562 cells.Imatinib (4 μmol/L)induced expression of Williams-Beuren syndrome transcription factor (WSTF),but not wild-type p53-induced phosphatase 1 (Wip1)in K562 cells.Conclusion:The caspase-3/Mst1 pathway is required for H2AX C-terminal phosphorylation at Ser139 and Tyr142 and subsequent apoptosis in Bcr-Abl-positive K562 cells induced by imatinib.

  20. Jak2 inhibition deactivates Lyn kinase through the SET–PP2A–SHP1 pathway, causing apoptosis in drug-resistant cells from chronic myelogenous leukemia patients

    OpenAIRE

    Samanta, AK; Chakraborty, SN; Wang, Y.; Kantarjian, H; Sun, X.; Hood, J; Perrotti, D; Arlinghaus, RB

    2009-01-01

    Chronic myelogenous leukemia (CML) patients treated with imatinib mesylate (IM) become drug resistant by mutations within the kinase domain of Bcr–Abl, and by other changes that cause progression to advanced stage (blast crisis) and increased expression of the Lyn tyrosine kinase, the regulation of which is not understood yet. In Bcr–Abl+ cells inhibition of Jak2, a downstream target of Bcr–Abl, by either Jak2 inhibitors or Jak2-specific short interfering RNA (siRNA) reduced the level of the ...

  1. Acute myelogenous leukemia and acute leukemic appendicitis: A case report

    Institute of Scientific and Technical Information of China (English)

    Po-Jen Hsiao; Shih-Ming Kuo; Jia-Hong Chen; Hsuen-Fu Lin; Pau-Ling Chu; Shih-Hua Lin; Ching-Liang Ho

    2009-01-01

    Acute myelogenous leukemia (AML) can involve the gastrointestinal tract but rarely involves the appendix.We report a male patient who had 1 year partial remission from AML and who presented with apparent acute appendicitis as the initial manifestation of leukemia relapse. Pathological findings of the appendix revealed transmural infiltrates of myeloblasts, whichindicated a diagnosis of leukemia. Unfortunately, the patient died from progression of the disease on the 19th d after admission. Although leukemic cell infiltration of the appendix is uncommon, patients with leukemia relapse can present with symptoms mimicking acute appendicitis.

  2. Resistance to BN myelogenous leukemia in rat radiation chimeras

    International Nuclear Information System (INIS)

    Lewis → LBNFl rat radiation chimeras showed marked resistance to transplanted BN myelogenous leukemia when compared to naive LBNFl, LBNFl → LBNFl, or BN → LBNFl. This occurred in the absence of overt graft versus host disease or of anti-BN response in mixed lymphocyte culture. Bone marrow specific antigens may serve as the target of the resistance mechanism. (author)

  3. Modulation of Akt and ERK1/2 pathways by resveratrol in chronic myelogenous leukemia (CML cells results in the downregulation of Hsp70.

    Directory of Open Access Journals (Sweden)

    Soumyajit Banerjee Mustafi

    Full Text Available BACKGROUND: Resveratrol is known to downregulate the high endogenous level of Heat shock protein 70 (Hsp70 in Chronic Myelogenous Leukemia (CML K562 cells and induce apoptosis. Since Heat Shock Factor 1 (HSF1 controls transcription of Hsp70, we wanted to probe the signaling pathways responsible for transcriptional activation of HSF1. METHODOLOGY/PRINCIPAL FINDINGS: Cells exposed to 40microM Resveratrol rapidly abolished serine473 phosphorylation of Akt and significantly reduced its kinase activity. Inactivation of Akt pathway by Resveratrol subsequently blocked serine9 phosphorylation of Gsk3beta. Active non-phosphorylated Gsk3beta rendered HSF1 transcriptionally inactive and reduced Hsp70 production. Blocking PI3K/Akt activity also demonstrated similar effects on Hsp70 comparable to Resveratrol. Inactivation of Gsk3beta activity by inhibitors SB261763 or LiCl upregulated Hsp70. Resveratrol significantly modulated ERK1/2 activity as evident from hyper phosphorylation at T302/Y304 residues and simultaneous upregulation in kinase activity. Blocking ERK1/2 activation resulted in induction of Hsp70. Therefore, increase in ERK1/2 activity by Resveratrol provided another negative influence on Hsp70 levels through negative regulation of HSF1 activity. 17-allylamino-17-demethoxygeldanamycin (17AAG, a drug that inhibits Hsp90 chaperone and degrades its client protein Akt concomitantly elevated Hsp70 levels by promoting nuclear translocation of HSF1 from the cytosol. This effect is predominantly due to inhibition of both Akt and ERK1/2 activation by 17AAG. Simultaneously treating K562 with Resveratrol and 17AAG maintained phosho-ERK1/2 levels close to untreated controls demonstrating their opposite effects on ERK1/2 pathway. Resveratrol was found not to interfere with Bcr-Abl activation in K562 cells. CONCLUSION/SIGNIFICANCE: Thus our study comprehensively illustrates that Resveratrol acts downstream of Bcr-Abl and inhibits Akt activity but stimulates ERK

  4. Pharmacoeconomic modeling of target therapy of chronic myeloid leukemia in remission

    OpenAIRE

    V. A. Shuvaev; K. M. Abdulkadyrov; I. S. Martynkevich; M. S. Fominykh

    2015-01-01

    The article presents example of modeling for pharmacoeconomical-founded choice of chronic myelogenous leukemia treatment strategy related to therapeutic efficacy and economical rationality. The economic model of chronic myelogenous leukemia diagnosis and treatment with Markov chain approach was constructed, based on modern national and international clinical guidelines. Pharmacoeconomical comparison of chronic myelogenous leukemia target therapy using first and second-generation tyrosine kina...

  5. Evaluation of multielements in human serum of patients with chronic myelogenous leukemia (CML) using SRTXRF; Avaliacao multielementar em soro humano de individuos portadores de leucemia mieloide cronica (LMC) usando SRTXRF

    Energy Technology Data Exchange (ETDEWEB)

    Leitao, Catarine Canellas Gondim

    2005-04-15

    In this work, trace elements were analyzed in serum of patients with chronic myelogenous leukemia (CML) by Total Reflection X-Ray Fluorescence using synchrotron radiation (SRTXRF). Chronic myelogenous leukemia (CML) affects the myeloid cells in the blood and affects 1 to 2 people per 100,000 and accounts for 7-20% cases of leukemia. Sixty patients with CML and sixty healthy volunteers (control group) were studied. Blood was collected into vacutainers without additives. Directly after collection, each blood sample was centrifuged at 3000 rev/min for 10 min in order to separate blood cells and suspended particles from blood serum. Sera were transferred into polyethylene tubes and stored in a freezer at 253 K. A 500 {sup m}u{sup L} serum quantity was spiked with Ga (50 {sup m}u{sup L} ) as internal standard. 10 {sup m}u{sup L} aliquots were pipetted on Perspex sample carrier. After deposition, the samples were left to dry under an infrared lamp. The measurements were performed at the X-Ray Fluorescence Beamline at Brazilian National Synchrotron Light Laboratory (LNLS), using a polychromatic beam. Standard solutions with gallium as internal standard were prepared for calibration system. It was possible to determine the concentrations of the following elements: P, S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Br and Rb. Starting from the ANOVA test was observed that the elements P, S, Ca, Cr, Mn, Fe, Cu and Rb presented real significant differences ({alpha} = 0.05) between groups (healthy subjects and CML patients) and Sex (males and females). (author)

  6. Systemic mastocytosis with associated acute myelogenous leukemia

    OpenAIRE

    Zhrebker, Leah; Cooper, Barry; Krause, John R.

    2014-01-01

    Systemic mastocytosis (SM) is a condition associated with a clonal neoplastic proliferation of mast cells. Approximately 40% of patients with SM present with an associated clonal hematological non–mast cell lineage disorder. Patients presenting with SM–acute myeloid leukemia (AML) have the worst prognosis. We present a case of a 62-year-old woman who was diagnosed with SM-AML. After initial treatment with a standard regimen of cytosine arabinoside (Ara-C)/idarubicin, her bone marrow showed re...

  7. Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

    Science.gov (United States)

    2013-07-03

    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); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  8. Splenic microabscesses in patients with acute myelogenous leukemia

    International Nuclear Information System (INIS)

    Eight patients with acute myelogenous leukemia in complete remission after induction chemotherapy got septic fever. Fever was unresponsive to broad-spectrum antibiotic therapy. Ultrasonography showed multiple 0,5-2 cm in diameter, anechoic densities and some 1-3 cm ''target'' appearances in spleen and liver. Computed tomography demonstrated multiple, round, 0,5-2 cm areas of diminished attenuation in spleen and liver, which did not enhance like the surrounding parenchyma. These microabscesses increased in size and number of lesions without equivalent antifungal therapy and decreased or disappeared after specific treatment. Candida-infection was assured by histologic liver specimen in four patients, fungal organisms were seen microscopically in liver-biopsy in one patient and at autopsy one patient was found to have candida disseminated to the spleen, liver, kidneys, lungand CNS. (orig.)

  9. Farnesyltransferase inhibitor tipifarnib inhibits Rheb prenylation and stabilizes Bax in acute myelogenous leukemia cells

    OpenAIRE

    Ding, Husheng; McDonald, Jennifer S.; Yun, Seongseok; Schneider, Paula A.; Peterson, Kevin L.; Flatten, Karen S.; Loegering, David A.; Ann L Oberg; Riska, Shaun M.; Huang, Shengbing; Sinicrope, Frank A.; Adjei, Alex A.; Judith E Karp; Meng, X. Wei; Kaufmann, Scott H.

    2014-01-01

    Although farnesyltransferase inhibitors have shown promising activity in relapsed lymphoma and sporadic activity in acute myelogenous leukemia, their mechanism of cytotoxicity is incompletely understood, making development of predictive biomarkers difficult. In the present study, we examined the action of tipifarnib in human acute myelogenous leukemia cell lines and clinical samples. In contrast to the Ras/MEK/ERK pathway-mediated Bim upregulation that is responsible for tipifarnib-induced ki...

  10. Molecular cytogenetic analyses of HIG, a novel human cell line carrying t(1;3)(p36.3;q25.3) established from a patient with chronic myelogenous leukemia in blastic crisis.

    Science.gov (United States)

    Hosoya, Noriko; Ogawa, Seishi; Motokura, Tohru; Hangaishi, Akira; Wang, Lili; Qiao, Ying; Nannya, Yasuhito; Kogi, Mieko; Hirai, Hisamaru

    2003-12-01

    Chromosomal abnormalities involving 1p36, 3q21, and/or 3q26 have been reported in a subset of myeloid neoplasms having characteristic dysmegakaryopoiesis, and the overexpression of EVI1 on 3q26 or of MEL1 on 1p36 has been implicated in their pathogenesis. We describe molecular cytogenetic analyses of a novel human cell line, HIG, established from a unique case in which a novel translocation t(1;3)(p36;q26) appeared as the sole additional chromosomal abnormality at the time of blastic transformation of chronic myelogenous leukemia. The patient displayed clinical features resembling those of the 3q21q26 syndrome. The HIG cell line retained der(1)t(1;3)(p36;q26) but lost t(9;22)(q34;q11). To identify the relevant gene that would be deregulated by this translocation, we molecularly cloned the translocation's breakpoints. They were distant from the breakpoint cluster regions of the 3q21q26 syndrome or t(1;3)(p36;q21), and neither the EVI1 nor the MEL1 transcript was detected in the HIG cell line. None of the genes located within 150 kilobase pairs of the breakpoints were aberrantly expressed, suggesting that in this case other gene(s) more distant from the breakpoints are deregulated by possible remote effects. Further analyses of the deregulated genes in the HIG cell line should provide important insight into the mechanisms involved in these types of leukemias.

  11. Molecular cytogenetic analyses of HIG, a novel human cell line carrying t(1;3)(p36.3;q25.3) established from a patient with chronic myelogenous leukemia in blastic crisis.

    Science.gov (United States)

    Hosoya, Noriko; Ogawa, Seishi; Motokura, Tohru; Hangaishi, Akira; Wang, Lili; Qiao, Ying; Nannya, Yasuhito; Kogi, Mieko; Hirai, Hisamaru

    2003-12-01

    Chromosomal abnormalities involving 1p36, 3q21, and/or 3q26 have been reported in a subset of myeloid neoplasms having characteristic dysmegakaryopoiesis, and the overexpression of EVI1 on 3q26 or of MEL1 on 1p36 has been implicated in their pathogenesis. We describe molecular cytogenetic analyses of a novel human cell line, HIG, established from a unique case in which a novel translocation t(1;3)(p36;q26) appeared as the sole additional chromosomal abnormality at the time of blastic transformation of chronic myelogenous leukemia. The patient displayed clinical features resembling those of the 3q21q26 syndrome. The HIG cell line retained der(1)t(1;3)(p36;q26) but lost t(9;22)(q34;q11). To identify the relevant gene that would be deregulated by this translocation, we molecularly cloned the translocation's breakpoints. They were distant from the breakpoint cluster regions of the 3q21q26 syndrome or t(1;3)(p36;q21), and neither the EVI1 nor the MEL1 transcript was detected in the HIG cell line. None of the genes located within 150 kilobase pairs of the breakpoints were aberrantly expressed, suggesting that in this case other gene(s) more distant from the breakpoints are deregulated by possible remote effects. Further analyses of the deregulated genes in the HIG cell line should provide important insight into the mechanisms involved in these types of leukemias. PMID:14704036

  12. Fangchinoline induces G0/G1 arrest by modulating the expression of CDKN1A and CCND2 in K562 human chronic myelogenous leukemia cells

    Science.gov (United States)

    WANG, YUPING; CHEN, JIE; WANG, LIN; HUANG, YUJI; LENG, YE; WANG, GUIYING

    2013-01-01

    Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease caused by the oncoprotein BCR-ABL, which exhibits a constitutive tyrosine kinase activity. Imatinib mesylate (IM), an inhibitor of the tyrosine kinase activity of BCR-ABL, has been used as a first-line therapy for CML. However, IM is less effective in the accelerated phase and blastic phases of CML and certain patients develop IM resistance due to the mutation and amplification of the BCR-ABL gene. Fangchinoline, an important chemical constituent from the dried roots of Stephaniae tetrandrae S. Moore, exhibits significant antitumor activity in various types of cancers, including breast, prostate and hepatocellular carcinoma. However, the effects and the underlying mechanisms of fangchinoline in CML remain unclear. In the present study, we identified that fangchinoline inhibits cell proliferation in a dose- and time-dependent manner in K562 cells derived from the blast crisis of CML. Additional experiments revealed that fangchinoline induces cell cycle arrest at the G0/G1 phase and has no effect on apoptosis, which is mediated through the upregulation of cyclin-dependent kinase (CDK)-N1A and MCL-1 mRNA levels, as well as the downregulation of cyclin D2 (CCND2) mRNA levels. These findings suggest the potential of fangchinoline as an effective antitumor agent in CML. PMID:23596478

  13. Therapeutic Autologous Lymphocytes and Aldesleukin in Treating Patients With High-Risk or Recurrent Myeloid Leukemia After Undergoing Donor Stem Cell Transplant

    Science.gov (United States)

    2011-07-12

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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); Blastic Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia

  14. Further phenotypic characterization of the primitive lineage− CD34+CD38−CD90+CD45RA− hematopoietic stem cell/progenitor cell sub-population isolated from cord blood, mobilized peripheral blood and patients with chronic myelogenous leukemia

    International Nuclear Information System (INIS)

    The most primitive hematopoietic stem cell (HSC)/progenitor cell (PC) population reported to date is characterized as being Lin−CD34+CD38−CD90+CD45R. We have a long-standing interest in comparing the characteristics of hematopoietic progenitor cell populations enriched from normal subjects and patients with chronic myelogenous leukemia (CML). In order to investigate further purification of HSCs and for potential targetable differences between the very primitive normal and CML stem/PCs, we have phenotypically compared the normal and CML Lin−CD34+CD38−CD90+CD45RA− HSC/PC populations. The additional antigens analyzed were HLA-DR, the receptor tyrosine kinases c-kit and Tie2, the interleukin-3 cytokine receptor, CD33 and the activation antigen CD69, the latter of which was recently reported to be selectively elevated in cell lines expressing the Bcr-Abl tyrosine kinase. Notably, we found a strikingly low percentage of cells from the HSC/PC sub-population isolated from CML patients that were found to express the c-kit receptor (<1%) compared with the percentages of HSC/PCs expressing the c-kitR isolated from umbilical cord blood (50%) and mobilized peripheral blood (10%). Surprisingly, Tie2 receptor expression within the HSC/PC subset was extremely low from both normal and CML samples. Using in vivo transplantation studies, we provide evidence that HLA-DR, c-kitR, Tie2 and IL-3R may not be suitable markers for further partitioning of HSCs from the Lin−CD34+CD38−CD90+CD45RA− sub-population

  15. The clinically relevant pharmacogenomic changes in acute myelogenous leukemia.

    Science.gov (United States)

    Emadi, Ashkan; Karp, Judith E

    2012-08-01

    Acute myelogenous leukemia (AML) is an extremely heterogeneous neoplasm with several clinical, pathological, genetic and molecular subtypes. Combinations of various doses and schedules of cytarabine and different anthracyclines have been the mainstay of treatment for all forms of AMLs in adult patients. Although this combination, with the addition of an occasional third agent, remains effective for treatment of some young-adult patients with de novo AML, the prognosis of AML secondary to myelodysplastic syndromes or myeloproliferative neoplasms, treatment-related AML, relapsed or refractory AML, and AML that occurs in older populations remains grim. Taken into account the heterogeneity of AML, one size does not and should not be tried to fit all. In this article, the authors review currently understood, applicable and relevant findings related to cytarabine and anthracycline drug-metabolizing enzymes and drug transporters in adult patients with AML. To provide a prime-time example of clinical applicability of pharmacogenomics in distinguishing a subset of patients with AML who might be better responders to farnesyltransferase inhibitors, the authors also reviewed findings related to a two-gene transcript signature consisting of high RASGRP1 and low APTX, the ratio of which appears to positively predict clinical response in AML patients treated with farnesyltransferase inhibitors.

  16. Inhibition of pentose phosphate pathway suppresses acute myelogenous leukemia.

    Science.gov (United States)

    Chen, Yan; Xu, Qian; Ji, Dexiang; Wei, Yanlin; Chen, Huamei; Li, Tingting; Wan, Bolin; Yuan, Liya; Huang, Ruibin; Chen, Guoan

    2016-05-01

    Pentose phosphate pathway (PPP) is a metabolic pathway that generates NADPH and pentose. PPP genes have been reported to be primarily or secondarily upregulated in many cancers. We aimed to study the general alteration of PPP in acute myelogenous leukemia (AML). We performed data mining and analysis of the Cancer Genome Atlas (TCGA) AML dataset for genetic alteration of the PPP gene set. In vitro studies including proliferation, migration, and invasion assays, together with metabolite consumption and oxidation assays, were performed. PPP genes were upregulated in 61 % of patients with AML. The majority of altered cases were expression changes measured by RNA sequencing. Expressions of critical PPP genes such as G6PD, PFKL, PFKP, and PGLS were consistently upregulated in all altered cases. Altered PPP is not associated with survival or disease relapse. PPP inhibition using 6-aminonicotinamide (6AN) increases glucose oxidative metabolism in AML. 6AN decreased the glucose oxidation and increased fatty acid oxidation. Here, we showed that PPP inhibition increased glucose oxidative metabolism in AML. PPP inhibition suppressed growth, migration, and invasion of AML, but not colony formation. PPP plays an important role in AML. Our results could contribute to the development of novel targeted treatment.

  17. What Is Chronic Myeloid Leukemia?

    Science.gov (United States)

    ... leukemia? Next Topic Normal bone marrow and blood What is chronic myeloid leukemia? Cancer starts when cells ... their treatment is the same as for adults. What is leukemia? Leukemia is a cancer that starts ...

  18. 慢性髓细胞性白血病病人骨髓单个核细胞中差异表达基因的筛选%Screen Differential Expressed Genes in Marrow Mononuclearcell of Chronic Myelogenous Leukemia Patient

    Institute of Scientific and Technical Information of China (English)

    王蜀燕; 孙朝晖; 危敏; 马文丽

    2011-01-01

    Objective: To screen differential expressed genes in marrow mononuclearcell of chronic myelogenous leukemia (CML) patient in order to develop the mechanism of CML.Methods: RNA were extracted in marrow mononuclearcell of both normal person and CML patient marked with digoxin.Differential expressed genes were analyzed by ABI 1700 bioarray and sorted by Jubilant physiology/disease categories.Results: A total of 6706 genes had significant differential expressed 43 genes relating to CML which have 13 genes up-regulated relating to signal transduction, protein metabolism and modification, nucleoside, nucleotide and nucleic acid metabolism, mRNA transcription, et al; while 30 genes down-regulated relating to nucleoside, nucleotide and nucleic acid metabolism, protein metabolism and modification, signal transduction, developmental processes, cell cycle, et al.Conclusion: 43 genes relating to CML have significant differential expressed, and play an important role in the process of CML malignant transformation.%目的:筛选慢性髓细胞性白血病(CML)病人骨髓单个核细胞与正常人的差异表达基因,探讨CML的发病机制.方法:提取正常人和CML病人单个核细胞的RNA,逆转录成cDNA并用地高辛标记,应用全基因组表达谱基因芯片对差异表达基因进行研究,采用Jubilant病理/疾病分类法对CML相关差异表达基因进行分析.结果:共筛选出CML相关差异表达基因43个,其中13个基因表达上调,30个基因表达下调,上调基因较多地参与信号转导、蛋白代谢、修饰、核酸代谢、mRNA转录调控等生物学过程;下调的基因主要涉及核酸代谢、信号转导、细胞及个体发育、细胞周期、免疫及防疫等方面.结论:CML病人与正常人的单个核细胞中有43个基因具有显著的表达差异,筛选获得的差异靶基因在CML恶性转化过程中发挥了重要作用,这为药物靶基因的筛选提供了理论基础.

  19. EphB1 Suppression in Acute Myelogenous Leukemia : Regulating the DNA Damage Control System

    NARCIS (Netherlands)

    Kampen, K. R.; Scherpen, F. J. G.; Garcia-Manero, G.; Yang, H.; Kaspers, G. J. L.; Cloos, J.; Zwaan, C. M.; van den Heuvel-Eibrink, M. M.; Kornblau, S. M.; De Bont, E. S. J. M.

    2015-01-01

    Loss of ephrin receptor (EphB1) expression may associate with aggressive cancer phenotypes; however, the mechanism of action remains unclear. To gain detailed insight into EphB1 function in acute myelogenous leukemia (AML), comprehensive analysis of EphB1 transcriptional regulation was conducted. In

  20. Development of hedge operator based fuzzy divergence measure and its application in segmentation of chronic myelogenous leukocytes from microscopic image of peripheral blood smear.

    Science.gov (United States)

    Ghosh, Madhumala; Chakraborty, Chandan; Konar, Amit; Ray, Ajoy K

    2014-02-01

    This paper introduces a hedge operator based fuzzy divergence measure and its application in segmentation of leukocytes in case of chronic myelogenous leukemia using light microscopic images of peripheral blood smears. The concept of modified discrimination measure is applied to develop the measure of divergence based on Shannon exponential entropy and Yager's measure of entropy. These two measures of divergence are compared with the existing literatures and validated by ground truth images. Finally, it is found that hedge operator based divergence measure using Yager's entropy achieves better segmentation accuracy i.e., 98.29% for normal and 98.15% for chronic myelogenous leukocytes. Furthermore, Jaccard index has been performed to compare the segmented image with ground truth ones where it is found that that the proposed scheme leads to higher Jaccard index (0.39 for normal, 0.24 for chronic myelogenous leukemia).

  1. Stages of Chronic Lymphocytic Leukemia

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Lymphocytic Leukemia Go to Health Professional Version Key Points Chronic ...

  2. What Is Chronic Lymphocytic Leukemia?

    Science.gov (United States)

    ... Topic Normal bone marrow, blood, and lymphoid tissue What is chronic lymphocytic leukemia? Cancer starts when cells ... body, including the lymph nodes, liver, and spleen. What is leukemia? Leukemia is a cancer that starts ...

  3. Development of therapeutic agents for elderly patients with acute myelogenous leukemia

    OpenAIRE

    Hourigan, Christopher S.; Judith E Karp

    2010-01-01

    Acute myelogenous leukemia (AML) is a disease more common in the elderly than the young. It is increasingly recognized that conventional cytotoxic chemotherapies used in children and young adults may not be appropriate in older adults because of diverse host- and disease-biology factors. This review highlights some of the most promising new treatment options that are being evaluated for older patients with AML. These options include CPX-351 (Celator Pharmaceuticals Inc), a unique liposomal fo...

  4. Common proviral integration region on mouse chromosome 7 in lymphomas and myelogenous leukemias induced by Friend murine leukemia virus.

    OpenAIRE

    Silver, J.; Kozak, C

    1986-01-01

    Friend murine leukemia virus (F-MuLV) induces a variety of hematopoietic neoplasms 2 to 12 months after inoculation into newborn mice. These neoplasms are clonal or oligoclonal and contain a small number of F-MuLV insertions in high-molecular-weight DNA. To investigate whether different tumors have proviral insertions in the same region, a provirus-cellular DNA junction fragment from an F-MuLV-induced myelogenous leukemia was cloned in lambda gtWES, and a portion of the flanking cellular DNA ...

  5. Survival after intestinal mucormycosis in acute myelogenous leukemia.

    Science.gov (United States)

    Parra, R; Arnau, E; Julia, A; Lopez, A; Nadal, A; Allende, E

    1986-12-15

    A young woman with acute myelocytic leukemia developed acute lower gastrointestinal bleeding immediately after a first remission induction of her leukemia. After the site of bleeding was located in the descending colon, a necrotic bleeding ulcer was resected. Histologic examination of the ulcer established the diagnosis of gastrointestinal mucormycosis. Treatment with amphotericin B was administered because of the high risk of dissemination. The patient has been followed for 9 months with no evidence of relapse of infection. Survival after gastrointestinal mucormycosis in acute leukemia has not previously been reported in the English language literature. Success in managing mucormycosis depends on the adherence to the recommended principles of early aggressive diagnostic measures, excisional surgery, amphotericin B therapy, and control of the underlying predisposing condition.

  6. PEGylated dendritic nanoarchitechture improves mean survival time of BDF1mice bearing myelogenous k -562 leukemia

    Institute of Scientific and Technical Information of China (English)

    Ramadoss Karthikeyan; Pureti Madhu Kumar; Palanirajan Vijayaraj Kumar

    2013-01-01

    Objective:To developing and exploring the use ofPEGylated poly(propylene imine) dendritic architecture for the delivery of an anti leukemic activity ofPrednisolone.Methods:For this study,PEGylated poly(propylene imine) dendritic architecture was synthesized and loaded with Prednisolone and targeted to the ascetic form of myelogenous leukemia k-562 cellines in hybrid miceBDF1, was used as tumor model.Theantileukemic activity was assessed by use of the criterionT/C%, whereT was the mean survival time(MST, days) of the drug treated mice, bearing k-562 leukemia andC- the mean survival time(MST, days) of untreated control animals, bearing the same leukemia cellines.Results:An antileukemic activity of the studiedPrednisolone loaded PEGylatedPolypropyleneimine(PPI) dendrimer was found to have increasing the mean survival time of the k-562 myelogenous leukemia cellines bearingBDF1 mice.The criterion“increase of life span”(ILS%) reached maximally270.1% for the drug loaded dendrimer.Conclusion:The studied dendrimer withPrednisolone showed lower toxicity with improved antileukemic activity in comparison with freePrednisolone.The further experiments in this field are in progress, aiming to design better dendritic formulations, with potential clinical use.

  7. HLA基因多态性与慢性粒细胞白血病的关联性研究%Correlation between polymorphism of HLA and chronic myelogenous leukemia

    Institute of Scientific and Technical Information of China (English)

    刘楠; 袁方; 梁飞; 金荔; 孙玉英; 奚永志

    2011-01-01

    目的 探讨人类白细胞抗原(HLA)基因多态性与慢性粒细胞白血病(CML)的关联性.方法 采用聚合酶链反应序列特异性引物(PCR-SSP)分型技术对234例CML患者以及1370例无血缘关系健康对照者进行HLA-A/B/C/DRB1/DQB1基因分型,采用病例对照研究方法进行基因频率、单倍型频率以及疾病发生相对危险度(RR)的研究.结果 CML患者中HLA-Cw3及Cw7的基因频率较对照组显著升高(P<0.05),其RR分别为1.4777和3.0595.而HLA-Cw4基因型频率则显著降低(P=0.0020),其RR为0.4331.扩展单倍型A2-B51-Cw14-DR9-DQ9与A11-B13-Cw3-DR12-DQ07的频率亦有显著性差异(P<0.05),其RR分别为3.1027和3.1606.两位点单倍型A2-Cw3、A24-Cw3、B15-Cw1与B40-Cw3的频率也存在显著性差异(P<0.05),其RR分别为2.5574、2.2544、3.8587及1.6853.结论 通过大样本量的病例对照研究HLA基因多态性与CML之间的关联性探讨取得了初步结果:HLA-Cw3及Cw7与CML的易感性相关;HLA-Cw4则与CML发生呈负相关,可能是CML的保护性基因;某些HLA单倍型或扩展单倍型亦与CML的发生有关.%Objective To study the correlation between genetic polymorphism of human leukocyte antigen (HLA) and chronic myelogenous leukemia (CML). Methods 234 CML patients and 1370 healthy unrelated ones as the control group were genotyped by polymeraee chain reaction sequence-specific primers (PCR-SSP) typing method for HLA-A/B/C/DRB1/DQB1 loci. The results of the two groups were analyzed by case control study method for gene frequencies, haplotype frequencies as well as the relative risk (RR) of disease. Results The gene frequencies of HLA-Cw3 and Cw7 in CML group were significantly higher ( P < 0. 05 )than in control group, and the RR was 1. 4777 and 3.0595 ,respectively. However, H LA-Cw4 frequency was significantly lower(P = 0. 0020) in CML group, and its RR was 0.4331. The extended haplotype frequencies of A2-B51-Cw14-DR9-DQ9 and A11-B13-Cw3-DR12-DQ07 were also

  8. Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-10-29

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; 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); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  9. Isolated Biliary Granulocytic Sarcoma Followed by Acute Myelogeneous Leukemia with Multilineage Dysplasia: A Case Report and Literature Review

    OpenAIRE

    Sung, Chang Ohk; Ko,Young Hyeh; Park, Cheol Keun; Jang, Kee Taek; Heo, Jin Seok

    2006-01-01

    Granulocytic sarcoma is a rare extramedullary tumor composed of myeloid progenitor cells. Primary involvement of the biliary tract without evidence of leukemia is exceedingly rare. Here, we report an isolated biliary granulocytic sarcoma in a 30-yr-old man who presented with jaundice, fever, and chill without any evidence of leukemia. However, five months after the diagnosis, he developed acute myelogenous leukemia with multilineage dysplasia and chromosomal abnormality. A rare possibility of...

  10. The Effects of Hemodynamic Shear Stress on Stemness of Acute Myelogenous Leukemia (AML)

    Science.gov (United States)

    Raddatz, Andrew; Triantafillu, Ursula; Kim, Yonghyun (John)

    2015-11-01

    Cancer stem cells (CSCs) have recently been identified as the root cause of tumors generated from cancer cell populations. This is because these CSCs are drug-resistant and have the ability to self-renew and differentiate. Current methods of culturing CSCs require much time and money, so cancer cell culture protocols, which maximize yield of CSCs are needed. It was hypothesized that the quantity of Acute myelogenous leukemia stem cells (LSCs) would increase after applying shear stress to the leukemia cells based on previous studies with breast cancer in bioreactors. The shear stress was applied by pumping the cells through narrow tubing to mimic the in vivo bloodstream environment. In support of the hypothesis, shear stress was found to increase the amount of LSCs in a given leukemia population. This work was supported by NSF REU Site Award 1358991.

  11. The prognostic importance of polypharmacy in older adults treated for acute myelogenous leukemia (AML)

    OpenAIRE

    Elliot, Kathleen; Tooze, Janet A.; Geller, Rachel; Powell, Bayard L.; Pardee, Timothy S.; Ritchie, Ellen; Kennedy, LeAnne; Callahan, Kathryn E.; Klepin, Heidi D.

    2014-01-01

    We retrospectively evaluated the prognostic significance of polypharmacy and inappropriate medication use among 150 patients >60 years of age receiving induction chemotherapy for acute myelogenous leukemia (AML). After adjustment for age and comorbidity, increased number of medications at diagnosis (≥4 vs. ≤1) was associated with increased 30-day mortality (OR=9.98, 95% CI=1.18–84.13), lower odds of complete remission status (OR=0.20, 95% CI=0.06–0.65), and higher overall mortality (HR=2.13, ...

  12. Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype.

    Science.gov (United States)

    Cazzaniga, Giovanni; Dell'Oro, Maria Grazia; Mecucci, Cristina; Giarin, Emanuela; Masetti, Riccardo; Rossi, Vincenzo; Locatelli, Franco; Martelli, Massimo F; Basso, Giuseppe; Pession, Andrea; Biondi, Andrea; Falini, Brunangelo

    2005-08-15

    Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein involved in leukemia-associated chromosomal translocations, and it regulates the alternate reading frame (ARF)-p53 tumor-suppressor pathway. Recently, it has been demonstrated that mutations of the NPM1 gene alter the protein at its C-terminal, causing its cytoplasmic localization. Cytoplasmic NPM was detected in 35% of adult patients with primary non-French-American-British (FAB) classification M3 acute myeloid leukemia (AML), associated mainly with normal karyotype. We evaluated the prevalence of the NPM1 gene mutation in non-M3 childhood AML patients enrolled in the ongoing Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP-AML02) protocol in Italy. NPM1 mutations were found in 7 (6.5%) of 107 successfully analyzed patients. NPM1-mutated patients carried a normal karyotype (7/26, 27.1%) and were older in age. Thus, the NPM1 mutation is a frequent abnormality in AML patients without known genetic marker; the mutation may represent a new target to monitor minimal residual disease in AML and a potential candidate for alternative and targeted treatments.

  13. Deorphanization and characterization of the ectopically expressed olfactory receptor OR51B5 in myelogenous leukemia cells

    Science.gov (United States)

    Manteniotis, S; Wojcik, S; Göthert, J R; Dürig, J; Dührsen, U; Gisselmann, G; Hatt, H

    2016-01-01

    The ectopic expression of olfactory receptors (ORs) in the human body has been of major interest in the past decade. Several studies have reported the expression of ORs not only in healthy tissues such as heart, sperm or skin cells, but also in cancerous tissues of the liver, prostate or intestine. In the present study, we detected the expression of OR51B5 in the chronic myelogenous leukemia (CML) cell line K562 and in white blood cell samples of clinically diagnosed acute myelogenous leukemia (AML) patients by reverse transcription-PCR and immunocytochemical staining. The known OR51B5 ligand isononyl alcohol increased the levels of intracellular Ca2+ in both AML patient blood cells and K562 cells. With calcium imaging experiments, we characterized in greater detail the OR51B5-mediated signaling pathway. Here, we observed an involvement of adenylate cyclase and the downstream L-type and T-type calcium channels. In addition, the activation of OR51B5 leads to an inhibition of cell proliferation in K562 cells. In western blot experiments, we found that incubation with isononyl alcohol led to a reduction in p38-MAPK (mitogen-activated protein kinase) phosphorylation that might be responsible for the decreased cell proliferation. In the present study, we characterized the OR51B5-mediated signaling pathway downstream of the activation with isononyl alcohol, which leads to reduced proliferation and therefore provide a novel pharmacological target for CML and AML, the latter of which remains difficult to treat. PMID:27551504

  14. Myelogenous leukemia in a bearded dragon (Acanthodraco vitticeps).

    Science.gov (United States)

    Tocidlowski, M E; McNamara, P L; Wojcieszyn, J W

    2001-03-01

    A 3-yr-old bearded dragon (Acanthodraco vitticeps) presented with lethargy, a swollen right elbow joint, inability to move its rear limbs normally, and marked leukocytosis. The majority of leukocytes were an abnormal mononuclear lymphoid-type cell with a high nuclear to cytoplasmic ratio, a slightly blue cytoplasm, nuclei with coarsely granular chromatin, and some nuclear clefts. Acute leukemia of lymphoid or myeloid origin was tentatively diagnosed. The abnormal mononuclear leukocyte cell population stained positively for the myeloid cytochemical stains: peroxidase, chloroacetate esterase, and L1-calprotectin. The abnormal cell population of the peripheral blood did not stain with the lymphoid cytochemical stains: alpha-naphthyl butyrate esterase, CD3, and CD79a.

  15. Myelogenous leukemia in a bearded dragon (Acanthodraco vitticeps).

    Science.gov (United States)

    Tocidlowski, M E; McNamara, P L; Wojcieszyn, J W

    2001-03-01

    A 3-yr-old bearded dragon (Acanthodraco vitticeps) presented with lethargy, a swollen right elbow joint, inability to move its rear limbs normally, and marked leukocytosis. The majority of leukocytes were an abnormal mononuclear lymphoid-type cell with a high nuclear to cytoplasmic ratio, a slightly blue cytoplasm, nuclei with coarsely granular chromatin, and some nuclear clefts. Acute leukemia of lymphoid or myeloid origin was tentatively diagnosed. The abnormal mononuclear leukocyte cell population stained positively for the myeloid cytochemical stains: peroxidase, chloroacetate esterase, and L1-calprotectin. The abnormal cell population of the peripheral blood did not stain with the lymphoid cytochemical stains: alpha-naphthyl butyrate esterase, CD3, and CD79a. PMID:12790401

  16. Induction of differentiation of myelogenous leukemia cells by humulone, a bitter in the hop.

    Science.gov (United States)

    Honma, Y; Tobe, H; Makishima, M; Yokoyama, A; Okabe-Kado, J

    1998-07-01

    The active form of vitamin D, 1alpha,25-dihydroxyvitamin D3 (VD3), inhibits proliferation and induces differentiation of myelomonocytic leukemia cells, but its clinical use is limited by the adverse effect of hypercalcemia. VD3 mobilizes calcium stores from bone by inducing the dissolution of bone mineral and matrix. We have recently found that humulone, a bitter in the hop extract for beer brewing, effectively inhibits bone resorption. In this study we examined the effect of humulone on the differentiation of human myelogenous leukemia cells. Humulone alone inhibited the growth of monoblastic leukemia U937 cells while only slightly increasing differentiation markers such as nitroblue tetrazolium (NBT)-reducing and lysozyme activities. Humulone effectively enhanced the differentiation-inducing action of VD3. Other myelomonocytic leukemia cells were induced to differentiate by VD3 and this was also enhanced by humulone. Since humulone is a less-toxic inhibitor of bone resorption, the combination of humulone and VD3 may be useful in differentiation therapy of myelomonocytic leukemia.

  17. Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells.

    Science.gov (United States)

    Pei, Shanshan; Minhajuddin, Mohammad; Callahan, Kevin P; Balys, Marlene; Ashton, John M; Neering, Sarah J; Lagadinou, Eleni D; Corbett, Cheryl; Ye, Haobin; Liesveld, Jane L; O'Dwyer, Kristen M; Li, Zheng; Shi, Lei; Greninger, Patricia; Settleman, Jeffrey; Benes, Cyril; Hagen, Fred K; Munger, Joshua; Crooks, Peter A; Becker, Michael W; Jordan, Craig T

    2013-11-22

    The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34(+)) leukemic versus normal specimens. Our data indicate that CD34(+) AML cells have elevated expression of multiple glutathione pathway regulatory proteins, presumably as a mechanism to compensate for increased oxidative stress in leukemic cells. Consistent with this observation, CD34(+) AML cells have lower levels of reduced glutathione and increased levels of oxidized glutathione compared with normal CD34(+) cells. These findings led us to hypothesize that AML cells will be hypersensitive to inhibition of glutathione metabolism. To test this premise, we identified compounds such as parthenolide (PTL) or piperlongumine that induce almost complete glutathione depletion and severe cell death in CD34(+) AML cells. Importantly, these compounds only induce limited and transient glutathione depletion as well as significantly less toxicity in normal CD34(+) cells. We further determined that PTL perturbs glutathione homeostasis by a multifactorial mechanism, which includes inhibiting key glutathione metabolic enzymes (GCLC and GPX1), as well as direct depletion of glutathione. These findings demonstrate that primitive leukemia cells are uniquely sensitive to agents that target aberrant glutathione metabolism, an intrinsic property of primary human AML cells. PMID:24089526

  18. Molecular genetics of chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia

    OpenAIRE

    Li, Bing; Gale, Robert Peter; Xiao, Zhijian

    2014-01-01

    According to the 2008 World Health Organization classification, chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia are rare diseases. The remarkable progress in our understanding of the molecular genetics of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms has made it clear that there are some specific genetic abnormalities in these 3 rare diseases. At the same time, there is considerable overlap among these disord...

  19. Development and evaluation of drug-antibody conjugates for the treatment of human myelogenous leukemia

    International Nuclear Information System (INIS)

    An immune serum to the Ph1+ human myelogenous leukemia cell line, K-562, was developed in goats. Following exhaustive absorptions, the antiserum and its immunoglobulin (Ig) fraction were highly cytotoxic for the homologenous cells in vitro in the presence of complement. In a nude mouse-human myelogenous leukemia model system, the Ig inhibits the growth and proliferation of myelosarcomas made up of K-562 cells. At the concentration of 6 mg or more, and beginning at 7 days after transplantation of myelosarcomas in nude mice, the administration of immunoglobulins resulted in the total suppression and subsequent elimination of the tumors. The dose-response relationship between the amount of Ig injected and the growth of myelosarcomas was demonstrated to be linear i.e., the extent of inhibition of tumor growth was directly dependent upon the dose of Ig given. Also, the uptake of 125I-labelled immunoglobulins by the K-562 myelosarcomas was at least 6-fold higher than that of the corresponding preimmune globulins

  20. Mannosylerythritol lipid induces granulocytic differentiation and inhibits the tyrosine phosphorylation of human myelogenous leukemia cell line K562

    OpenAIRE

    Isoda, Hiroko; Nakahara, Tadaatsu

    1997-01-01

    Mannosylerythritol lipid (MEL), which induced granulocytic differentiation of human promyelocytic leukemia cell line HL60, also induced differentiation of human myelogenous leukemia cell line K562. MEL inhibited insulin-dependent cell proliferation and induced leukocyte esterase activity of K562 cells. MEL markedly increased the differentiation-associated characteristics in granulocytes, such as nitroblue tetrazolium (NBT) reducing ability, expression of Fc receptors, and phagocytic activity ...

  1. HLA-DRB1基因多态性与急性淋巴细胞白血病和慢性髓性白血病易感性关联的研究%Association between HLA-DRB1 allele polymorphism and susceptibility to acute lymphoblastic leukemia and chronic myelogenous leukemia in Chinese Han

    Institute of Scientific and Technical Information of China (English)

    曹孟德; 陈宗德; 苏堤; 秦东春; 岳保红; 苏天水; 燕桂香; 盛光耀

    2001-01-01

    目的探讨急性淋巴细胞白血病(ALL)和慢性髓性白血病(CML)易感性与HLA-DRB1基因多态性之间的关联性,找出急性淋巴细胞白血病和慢性髓性白血病的易感基因。方法采用序列特异性引物聚合酶链反应(PCR-SSP)DNA分型技术对56例ALL患者、48例CML患者和105例健康对照进行了HLA-DRB1基因分型。结果 ALL患者组与HLA-DR7基因关联,基因频率为24.1%,RR =2.56,χ2=7.34,P<0.01;CML患者组与HLA-DR4基因关联,基因频率为22.9%,RR =5.076,χ2=17.88,P<0.01;其他等位基因频率在实验组与对照组间差异无显著性。结论提示在河南汉族人群中,HLA-DR7与ALL有关联,HLA-DR4与CML有关联。%Objective To explore the possible association between HLA-DRB1 allele polymorphism and susceptibility to acute lymphoblastic leukemia(ALL) as well as chronic myelogenous leukemia(CML) in Chinese He′nan Han People and to find the predisposing genes of ALL and CML. Methods 105 normal people and 56 ALL patients and 48 CML patients of He′nan Han nationality were tested for HLA-DRB1 by polymerase chain reaction with sequence specific primers(PCR-SSP). Results Compared with normal controls, the frequency of HLA-DR7 was significantly increased in ALL group with a relative risk (RR) as 2.56 (χ2 =7.34, P<0.01) and with an etiological fraction (EF) as 0.29; the frequencies of other DRB1 alleles were not significantly increased in the ALL group. The frequency of HLA-DR4 was significantly increased in CML patient group, with a relative risk (RR) as 5.076 (χ2=17.88, P<0.01) and with an etiological fraction (EF) as 0.18, while the frequencies of other DRB1 alleles were not significantly increased in CML group. Conclusion These results showed that susceptibility to ALL is positively related to HLA-DR7 gene and susceptibility to CML is strongly correlated with HLA-DR4 gene.

  2. Acute myelogenous leukemia switch lineage upon relapse to acute lymphoblastic leukemia: a case report

    OpenAIRE

    Dorantes-Acosta, Elisa; Arreguin-Gonzalez, Farina; Rodriguez-Osorio, Carlos A; Sadowinski, Stanislaw; Pelayo, Rosana; Medina-Sanson, Aurora

    2009-01-01

    Acute leukemia, the most common form of cancer in children, accounts for approximately 30% of all childhood malignancies, with acute lymphoblastic leukemia being five times more frequent than acute myeloid leukemia. Lineage switch is the term that has been used to describe the phenomenon of acute leukemias that meet the standard French-American-British system criteria for a particular lineage (either lymphoid or myeloid) upon initial diagnosis, but meet the criteria for the opposite lineage a...

  3. Nilotinib for the treatment of chronic myeloid leukemia: An evidence-based review

    OpenAIRE

    Elias Jabbour; Jorge Cortes; Hagop Kantarjian

    2009-01-01

    Elias Jabbour, Jorge Cortes, Hagop KantarjianDepartment of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USAIntroduction: Chronic myelogenous leukemia (CML) is a progressive and often fatal hematopoietic neoplasm. The Bcr-Abl tyrosine kinase inhibitor imatinib mesylate represented a major therapeutic advance over conventional CML therapy, with more than 90% of patients obtaining complete hematologic response, and 70%–80% of patients achieving a complete...

  4. Radiation-associated chronic myelogenous leukaemia in younger people

    International Nuclear Information System (INIS)

    Chronic myelogenous leukaemia (CML) is known to be induced by exposure to ionizing radiation, as is acute leukaemia. However, CML has been recorded only rarely as a complication of radiation exposure early in life. During the period from 1973 to 1976, 75 patients with CML were admitted to Roswell Park Memorial Institute (RPMI). In addition, 64 patients admitted to RPMI previously were also available for study in 1973. Among 79 patients who were born after 1925, information regarding radiation exposure was obtained in 89%; 49 were interviewed and 21 responded to a mailed questionnaire. Consultation with parents was achieved in 52 of the 70 responding cases (74%). Replies were obtained from 15 of the 18 patients below the age of 25, and were confirmed by parents or siblings in all instances. Replies to the mailed questionnaire were obtained from 45 age- and sex-matched controls. In addition to two patients already known to have radiation exposure for treatment of malignant neoplasms, these inquiries yielded a total of nine patients with histories of radiation exposure for benign conditions. Three had therapeutic irradiation, two for thymic enlargement and one for eczema. Three had exposure in utero by pelvimetry. Two had diagnostic exposure during the perinatal period and one had occupational exposure as a nurse. Four of these patients were below the age of 25. All nine patients had the Ph' chromosome. The course of CML in these patients was not different from that of other patients with Ph' chromosome-positive CML without a history of radiation exposure. A history of radiation exposure was elicited in one-fourth of the younger patients (<25) in this study, compared with one of 45 age- and sex-matched controls without leukaemia (p<0.02)

  5. Association of in vitro radiosensitivity and cancer in a family with acute myelogenous leukemia

    International Nuclear Information System (INIS)

    The γ-ray sensitivity of skin fibroblasts from six members of a cancer family was investigated using a colony-forming assay. Fibroblasts from the three members with cancer (two sisters with acute myelogenous leukemia and the mother with cervical carcinoma) showed a significant ( p > 0.05) increase in radiosensitivity, while three members without cancer (the father and two sons) showed a normal radioresponse. The possiblity that the increased γ-ray sensitivity was due to defective DNA repair was investigated using assays for DNA repair replication, single-strand break rejoining, and removal of enzyme-sensitive sites in γ-irradiated DNA. Results of these assays indicate that the kinetics of enzymatic repair of radiogenic DNA damage in general, and the rejoining of single-strand scissions and excision repair of base and sugar radioproducts in partigular, were the same in the cell lines from the sensitive and clinically normal family members

  6. Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  7. Chronic Myeloid Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  8. Treatment Options by Stage (Chronic Lymphocytic Leukemia)

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Lymphocytic Leukemia Go to Health Professional Version Key Points Chronic ...

  9. Treatment Option Overview (Chronic Lymphocytic Leukemia)

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Lymphocytic Leukemia Go to Health Professional Version Key Points Chronic ...

  10. Summary of the published Indian data on chronic myeloid leukemia.

    Science.gov (United States)

    Singhal, Manish K; Sengar, Manju; Nair, Reena

    2016-01-01

    Chronic myelogenous leukemia (LML) was recognized as a distinct entity in the mid-1800s. Since Nowell and Hunagerford initiated their research on CML in1960 our understanding in CML has been increasing. Imatinib became the preferred treatment from 2000 onwards as a result of its unprecedented success. The lack of structured Indian data on CML led to the formation of a CML data cansortuim which invited CML data albiet retro spartive form around the country including major cancer service providers both government and private. We provide a summary of published Indian data on CML here. PMID:27606306

  11. Haploidentical vs cord blood transplantation for adults with acute myelogenous leukemia

    Institute of Scientific and Technical Information of China (English)

    Melhem; Solh

    2014-01-01

    Hematopoeitic cell transplantation is established as a curative treatment for patients w acute myelogenous leukemia. Haploidentical family donor and umbilical cord blood(UCB) are alternative sources of stem cells for patients lacking a matched sibling or unrelated do-nor. The early challenges of transplant complications related to poor engraftment and graft-vs-host disease have been overcome with new strategies such as using 2 units and increased cell dose in UCB and T-cell deple-tion and post transplantation cyclophosphamide in hap-loidentical transplantation. The outcomes of alternative transplantation for acute leukemia were compared to other traditional graft sources. For patients lacking a matched sibling or unrelated donor, either strategy is a suitable option. The choice should rely mostly on the urgency of the transplantation and the available cell dose as well as the expertise available at the trans-plant center. This manuscript reviews the options of alternative donor transplantation and highlights recent advances in each of these promising transplantation options.

  12. Induction of differentiation and apoptosis- a possible strategy in the treatment of adult acute myelogenous leukemia.

    Science.gov (United States)

    Bruserud, O; Gjertsen, B T; Huang, Ts

    2000-01-01

    A differentiation block with accumulation of immature myeloid cells characterizes acute myelogenous leukemia (AML). However, native AML cells often show some morphological signs of differentiation that allow a classification into different subsets, and further differentiation may be induced by exposure to various soluble mediators, e.g., all trans-retinoic acid (ATRA) and several cytokines. Combination therapy with ATRA and chemotherapy should now be regarded as the standard treatment for the acute promyelocytic leukemia variant of AML. Several agents can induce leukemic cell differentiation for other AML subtypes, although these effects differ between patients. Differentiation may then be associated with induction of apoptosis, and differentiation-inducing therapy may therefore become useful in combination with intensive chemotherapy to increase the susceptibility of AML blasts to drug-induced apoptosis. However, it should be emphasized that differentiation and apoptosis can occur as separate events with different regulation in AML cells, and future studies in AML should therefore focus on: A) the identification of new agents with more predictable effects on differentiation and apoptosis; B) the use of clinical and laboratory parameters to define new subsets of AML patients in which differentiation/apoptosis induction has a predictable and beneficial effect, and C) further characterization of how AML blast sensitivity to drug-induced apoptosis is modulated by differentiation induction.

  13. Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia

    Directory of Open Access Journals (Sweden)

    Nishihori Taiga

    2010-10-01

    Full Text Available Abstract Optimal conditioning therapy for hematopoietic cell transplantation (HCT in acute myelogenous leukemia (AML remains undefined. We retrospectively compared outcomes of a consecutive series of 51 AML patients treated with oral busulfan (1 mg/kg every 6 hours for 4 days and cyclophosphamide (60 mg/kg IV × 2 days - (Bu/Cy with 100 consecutive AML patients treated with pharmacokinetic targeted IV busulfan (AUC

  14. "HLA Class II Allele and Haplotype Frequencies in Iranian Patients with Acute Myelogenous Leukemia and Control Group "

    Directory of Open Access Journals (Sweden)

    Abdolfattah Sarafnejad

    2006-09-01

    Full Text Available Previous studies have demonstrated some significant differences in HLA allele frequencies in leukemic patients and normal subjects. We have analyzed HLA class II alleles and haplotypes in 60 Iranian patients with acute myelogenous leukemia (AML and 180 unrelated normal subjects. Blood samples were collected after obtaining informed consents. From the patients and control DNA extraction and HLA typing were performed using PCR-SSP method. Significant positive association with the disease was found for HLA-DRB1*11 allele (35% vs. 24.7%, p=0.033. Two alleles including HLA-DRB4 and –DQB1*0303 were found to be significantly decreased in patients compared to controls. Regarding haplotype analysis, no significant association was found between case and control groups. It is suggested that HLA-DRB1*11 allele plays as a presumptive predisposing factor while the HLA-DRB4 and –DQB1*0303 alleles are suggested as protective genetic factors against acute myelogenous leukemia. Larger studies are needed to confirm and establish the role of these associations with acute myelogenous leukemia.

  15. Chronic Myeloid Leukemia In a Pregnant Woman: A Case Report

    Directory of Open Access Journals (Sweden)

    Aytekin Tokmak

    2015-12-01

    Full Text Available Chronic myeloid leukemia (CML is a rare disease in pregnancy. Our aim is to present a 37 weeks of pregnant woman with chronic myelogenous leukemia. A 27 Years in multigravi (gravida 5, parity: 4, at 37 weeks gestation was admitted with the diagnosis of painful pregnancy and CML. Physical examination findings were normal, complete blood count and peripheral blood smear results were consistent with CML. The patient was diagnosed CML in the 30th week of pregnancy and were treated with hydroxyurea and interferon. Treatment depends on the mother and the fetus did not develop any side effects. Our patient with CML is interesting due to lack of perinatal effects and take the diagnosis at an early age. CML diagnosed during pregnancy requires a multidisciplinary approach and hydroxyurea and interferon treatment on the mother and fetus are at low risk of inducing adverse effects. [Cukurova Med J 2015; 40(4.000: 811-813

  16. FR901228 in Treating Children With Refractory or Recurrent Solid Tumors or Leukemia

    Science.gov (United States)

    2013-01-15

    Blastic Phase Chronic Myelogenous Leukemia; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Chronic Myelogenous Leukemia; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  17. Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

    Science.gov (United States)

    2013-01-15

    Childhood Acute Erythroleukemia (M6); 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 Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  18. Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

    Science.gov (United States)

    2016-07-18

    B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  19. Ring chromosome 18 abnormality in acute myelogenous leukemia: the clinical dilemma

    Directory of Open Access Journals (Sweden)

    Malone Adriana K

    2010-07-01

    Full Text Available Abstract The ring chromosome is a circular, structural abnormality composed of either multiple chromosomes or a single chromosome with loss of genetic material at one or both ends. This chromosomal rearrangement is often unstable with frequent recombinations and may be accompanied by either loss or amplification of genetic material1. Considering that ring chromosomes are rare in acute myelogenous leukemia (AML, it is difficult to risk stratify patient prognosis, particularly when the ring chromosome occurs as the sole abnormality. Here we report a case of a ring chromosome 18 abnormality in a patient with newly diagnosed AML with monocytic differentiation. Cytogenetic analysis demonstrated 46, XY, r(18(p11q21 karyotype in 19 of 34 evaluated metaphase cells. The patient received induction chemotherapy and subsequent allogeneic cord blood transplant from a sex-matched donor, and remained in hematologic and cytogenetic remission for 120 days post transplant. Soon after, he developed post transplant lymphoproliferative disorder and died of multi-organ failure. Although r(18 chromosomal abnormalities were not classified in the recent updated evidence-and expert opinion-based recommendations for the diagnosis and management of AML (likely due to the small number of reported cases, the patient was treated as high risk with stem cell transplantation. This was based on the unstable nature of the ring chromosome and the poor outcomes described in the literature of patients with sole ring 18 abnormalities.

  20. Evolution of acute myelogenous leukemia stem cell properties after treatment and progression.

    Science.gov (United States)

    Ho, Tzu-Chieh; LaMere, Mark; Stevens, Brett M; Ashton, John M; Myers, Jason R; O'Dwyer, Kristen M; Liesveld, Jane L; Mendler, Jason H; Guzman, Monica; Morrissette, Jennifer D; Zhao, Jianhua; Wang, Eunice S; Wetzler, Meir; Jordan, Craig T; Becker, Michael W

    2016-09-29

    Most cancers evolve over time as patients initially responsive to therapy acquire resistance to the same drugs at relapse. Cancer stem cells have been postulated to represent a therapy-refractory reservoir for relapse, but formal proof of this model is lacking. We prospectively characterized leukemia stem cell populations (LSCs) from a well-defined cohort of patients with acute myelogenous leukemia (AML) at diagnosis and relapse to assess the effect of the disease course on these critical populations. Leukemic samples were collected from patients with newly diagnosed AML before therapy and after relapse, and LSC frequency was assessed by limiting dilution analyses. LSC populations were identified using fluorescent-labeled cell sorting and transplantation into immunodeficient NOD/SCID/interleukin 2 receptor γ chain null mice. The surface antigen expression profiles of pretherapy and postrelapse LSCs were determined for published LSC markers. We demonstrate a 9- to 90-fold increase in LSC frequency between diagnosis and relapse. LSC activity at relapse was identified in populations of leukemic blasts that did not demonstrate this activity before treatment and relapse. In addition, we describe genetic instability and exceptional phenotypic changes that accompany the evolution of these new LSC populations. This study is the first to characterize the evolution of LSCs in vivo after chemotherapy, identifying a dramatic change in the physiology of primitive AML cells when the disease progresses. Taken together, these findings provide a new frame of reference by which to evaluate candidate AML therapies in which both disease control and the induction of more advanced forms of disease should be considered. PMID:27421961

  1. Acute myelogenous leukemia developed after radioactive iodine therapy and palliative radiation therapy in metastatic papillary thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Tae Young; Kwak, Jae Sik; Oh, Kyung Suk; Lee, Seung Bai; Chung, Byung Sun; Kim, Eun Sil; Kim, Chong Soon [Hanil Hospital, Seoul (Korea, Republic of)

    1998-08-01

    Radioactive iodine treatment has been widely used for nearly 50 years in the treatment of thyroid cancer to ablate residual thyroid tissue after thyroidectomy and to treat metastatic disease. Leukemia is a rare complication associated with the radioactive iodine therapy. The occurrence of leukemia is known to be related to the cumulative dosage of I-131 more than 37 GBq (1 Ci) and also associated with the intervals of less than 12 months between the repeated doses. We report a case of a 52 year-old female patient with papillary cancer of thyroid who developed acute myelogenous leukemia after the total 20.4 GBq (550 mCi) of I-131 therapy over 3.2 years and palliative radiation therapy ( 3000 cGy) due to multiple bone metastasis of papillary cancer.

  2. Tratamento da recidiva da leucemia mielóide crônica após transplante de medula óssea alogênico utilizando mesilato de imatinibe: relato de três casos Treatment of chronic myelogenous leukemia relapse after allogeneic bone marrow transplantation with imatinib mesylate: report of three cases

    Directory of Open Access Journals (Sweden)

    Ronald Pallotta

    2006-06-01

    Full Text Available O mesilato de imatinibe (MI, inibidor seletivo da tirosinoquinase envolvido na patogênese da leucemia mielóide crônica (LMC, tem se constituído como terapia farmacológica de primeira linha para o tratamento desta doença. A infusão de linfócitos do doador (DLI tem sido considerada como tratamento padrão para recidiva da LMC após transplante de medula óssea (TMO alogênico, apesar de estar freqüentemente associado à ocorrência de doença do enxerto contra hospedeiro e mielossupressão. Por apresentar resultados satisfatórios e boa tolerabilidade no tratamento da LMC, os autores empregaram o mesilato de imatinib como terapêutica alternativa à DLI em pacientes que sofreram recidiva após o TMO. Obtiveram sucesso em dois casos, sendo que em um houve retorno comprovado do quimerismo do doador. No terceiro caso houve progressão da doença e o paciente foi encaminhado para segundo TMO. Desta forma, devido ao caráter recente do tema, este estudo descritivo sugere que esta opção terapêutica possa ser estudada como alternativa na recaída pós-TMO.Imatinib mesylate (MI, a selective tyrosine kinase inhibitor involved in the pathogenesis of chronic myelogenous leukemia (CML, has become the first-line treatment for this disease. Donor lymphocyte infusion (DLI has been considered as the standard treatment for relapse after allogeneic bone marrow transplantation (BMT, even though it is frequently associated with graft versus host disease and myelosuppression. Because of the satisfactory results and tolerance of the treatment of CML, the authors used MI as an alternative therapy for DLI in patients that relapsed after BMT. They obtained cytogenetic remission in two cases, with, in one case, proven conversion to the donor chimera. The third case evolved with progression of the disease and a second BMT was required. Since this is a new alternative, this descriptive study suggests it should be considered as an alternative therapy for relapse

  3. Pharmacoeconomic modeling of target therapy of chronic myeloid leukemia in remission

    Directory of Open Access Journals (Sweden)

    V. A. Shuvaev

    2015-01-01

    Full Text Available The article presents example of modeling for pharmacoeconomical-founded choice of chronic myelogenous leukemia treatment strategy related to therapeutic efficacy and economical rationality. The economic model of chronic myelogenous leukemia diagnosis and treatment with Markov chain approach was constructed, based on modern national and international clinical guidelines. Pharmacoeconomical comparison of chronic myelogenous leukemia target therapy using first and second-generation tyrosine kinase inhibitors was performed. The average direct cost for one patient and total budget impact in twenty years were calculated. Analysis was made based on costs of original imatinib and generics. We used the imatinib generics’ substitution experience as a scenario for the second generation TKIs. Under these conditions, more frequent therapy cessation with second generation TKIs resulted in nilotinib first line is cost saving over imatinib. We should note that theresults of our analysis were strongly dependent on the input parameters values. The Pharmacoeconomic modelling can forecast the budget burden and its future dynamics on the individual and national level. The results of such modelling could be of value in decision-making in national guidelines development and discussion with healthcare authorities.

  4. Pharmacoeconomic modeling of target therapy of chronic myeloid leukemia in remission

    Directory of Open Access Journals (Sweden)

    V. A. Shuvaev

    2014-01-01

    Full Text Available The article presents example of modeling for pharmacoeconomical-founded choice of chronic myelogenous leukemia treatment strategy related to therapeutic efficacy and economical rationality. The economic model of chronic myelogenous leukemia diagnosis and treatment with Markov chain approach was constructed, based on modern national and international clinical guidelines. Pharmacoeconomical comparison of chronic myelogenous leukemia target therapy using first and second-generation tyrosine kinase inhibitors was performed. The average direct cost for one patient and total budget impact in twenty years were calculated. Analysis was made based on costs of original imatinib and generics. We used the imatinib generics’ substitution experience as a scenario for the second generation TKIs. Under these conditions, more frequent therapy cessation with second generation TKIs resulted in nilotinib first line is cost saving over imatinib. We should note that theresults of our analysis were strongly dependent on the input parameters values. The Pharmacoeconomic modelling can forecast the budget burden and its future dynamics on the individual and national level. The results of such modelling could be of value in decision-making in national guidelines development and discussion with healthcare authorities.

  5. Pathologic rupture of the spleen in a patient with acute myelogenous leukemia and leukostasis

    Directory of Open Access Journals (Sweden)

    Gil Cunha De Santis

    2014-07-01

    Full Text Available Rupture of the spleen can be classified as spontaneous, traumatic, or pathologic. Pathologic rupture has been reported in infectious diseases such as infectious mononucleosis, and hematologic malignancies such as acute and chronic leukemias. Splenomegaly is considered the most relevant factor that predisposes to splenic rupture. A 66-year-old man with acute myeloid leukemia evolved from an unclassified myeloproliferative neoplasm, complaining of fatigue and mild upper left abdominal pain. He was pale and presented fever and tachypnea. Laboratory analyses showed hemoglobin 8.3 g/dL, white blood cell count 278 × 109/L, platelet count 367 × 109/L, activated partial thromboplastin time (aPTT ratio 2.10, and international normalized ratio (INR 1.60. A blood smear showed 62% of myeloblasts. The immunophenotype of the blasts was positive for CD117, HLA-DR, CD13, CD56, CD64, CD11c and CD14. Lactate dehydrogenase was 2384 U/L and creatinine 2.4 mg/dL (normal range: 0.7-1.6 mg/dL. Two sessions of leukapheresis were performed. At the end of the second session, the patient presented hemodynamic instability that culminated in circulatory shock and death. The post-mortem examination revealed infiltration of the vessels of the lungs, heart, and liver, and massive infiltration of the spleen by leukemic blasts. Blood volume in the peritoneal cavity was 500 mL. Acute leukemia is a rare cause of splenic rupture. Male gender, old age and splenomegaly are factors associated with this condition. As the patient had leukostasis, we hypothesize that this, associated with other factors such as lung and heart leukemic infiltration, had a role in inducing splenic rupture. Finally, we do not believe that leukapheresis in itself contributed to splenic rupture, as it is essentially atraumatic.

  6. Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Cowan-Jacob, Sandra W., E-mail: sandra.jacob@novartis.com; Fendrich, Gabriele; Floersheimer, Andreas; Furet, Pascal; Liebetanz, Janis; Rummel, Gabriele; Rheinberger, Paul; Centeleghe, Mario; Fabbro, Doriano; Manley, Paul W. [Novartis Institutes for Biomedical Research, Basel (Switzerland)

    2007-01-01

    A case study showing how the determination of multiple cocrystal structures of the protein tyrosine kinase c-Abl was used to support drug discovery, resulting in a compound effective in the treatment of chronic myelogenous leukaemia. Chronic myelogenous leukaemia (CML) results from the Bcr-Abl oncoprotein, which has a constitutively activated Abl tyrosine kinase domain. Although most chronic phase CML patients treated with imatinib as first-line therapy maintain excellent durable responses, patients who have progressed to advanced-stage CML frequently fail to respond or lose their response to therapy owing to the emergence of drug-resistant mutants of the protein. More than 40 such point mutations have been observed in imatinib-resistant patients. The crystal structures of wild-type and mutant Abl kinase in complex with imatinib and other small-molecule Abl inhibitors were determined, with the aim of understanding the molecular basis of resistance and to aid in the design and optimization of inhibitors active against the resistance mutants. These results are presented in a way which illustrates the approaches used to generate multiple structures, the type of information that can be gained and the way that this information is used to support drug discovery.

  7. The expression and clinical significance of survivin gene in leukemia

    Institute of Scientific and Technical Information of China (English)

    王艳

    2006-01-01

    Objective To investigate the expression of survivin in leukemia and the prognostic significance in acute leukemia(AL). Methods The expression of survivin mRNA was measured in 105 AL and 21 chronic myelogenous leukemia (CML) patients with semi-quantity reverse transcription (RT)-PCR.15 adults were tested as normal

  8. Anti-Tumor and Immune Enhancing Activities of Rice Bran Gramisterol on Acute Myelogenous Leukemia.

    Directory of Open Access Journals (Sweden)

    Somsuda Somintara

    Full Text Available Acute myelogenous leukemia (AML is a cancer of the blood that most commonly affects human adults. The specific cause of AML is unclear, but it induces abnormality of white blood cells that grow rapidly and accumulate in bone marrow interfering with the production and functions of the normal blood cells. AML patients face poor prognosis and low quality of life during chemotherapy or transplantation of hematopoietic stem cells due to the progressive impairment of their immune system. The goal of this study is to find natural products that have the potential to delay growth or eliminate the abnormal leukemic cells but cause less harmful effect to the body's immune system.The unsaponified fraction of Riceberry rice bran (RBDS and the main pure compound, gramisterol, were studied for cytotoxicity and biological activities in WEHI-3 cells and in the leukemic mouse model induced by transplantation of WEHI-3 cells intraperitoneally. In the in vitro assay, RBDS and gramisterol exerted sub-G1 phase cell cycle arrest with a potent induction of apoptosis. Both of them effectively decreased cell cycle controlling proteins (cyclin D1 and cyclin E, suppressed cellular DNA synthesis and mitotic division, and reduced anti-apoptosis Bcl-2 protein, but increased apoptotic proteins (p53 and Bax and activated caspase-3 enzyme in the intrinsic cell death stimulation pathway. In leukemic mice, daily feeding of RBDS significantly increased the amount of immune function-related cells including CD3+, CD19+, and CD11b+, and elevated the serum levels of IFN-γ, TNF-α, IL-2, and IL-12β cytokines, but suppressed IL-10 level. At the tumor sites, CD11b+ cells were polarized and became active phagocytotic cells. Treatment of mice normal immune cells with gramisterol alone or a combination of gramisterol with cytokines released from RBDS-treated leukemic mice splenocytes culture synergistically increased pSTAT1 transcriptional factor that up-regulated the genes controlling

  9. Comparative clinical study of Philadelphia chromosome -positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myelogenous leukemia%Ph+急性淋巴细胞白血病与慢性粒细胞白血病急淋变的比较研究

    Institute of Scientific and Technical Information of China (English)

    刘延方; 程远东; 王芳; 孟小莉; 董慧; 孙慧; 孙玲; 万鼎铭; 姜中兴; 刘林湘; 陈绍倩; 谢新生

    2012-01-01

    目的 探讨Ph染色体阳性急性淋巴细胞白血病(Ph+ ALL)与慢性粒细胞白血病急淋变的临床特点.方法 对21例Ph+ ALL患者及31例慢粒急淋变患者的临床资料进行回顾性对比分析.结果 Ph+ ALL与慢粒急淋变有以下区别:①慢粒急淋变肝脾肿大发生率(80.65%)比Ph+ ALL( 14.28%)高(P<0.05);②起病时慢粒急淋变外周血白细胞数比Ph+ ALL高(P<0.05);③Ph+ ALL完全缓解率(76.19%)比慢粒急淋变(48.39%)高(P<0.05).Ph+ ALL的中位生存期为(10.76±6.91)个月,而慢粒急淋变的中位生存期为(7.06±6.03)个月,差异有统计学意义(P<0.05).慢粒急淋变者完全缓解后Ph染色体持续存在,Ph+ ALL患者完全缓解后Ph染色体消失.两组患者年龄、性别、骨髓中原始加幼稚细胞数差异均无统计学意义(P>0.05).结论 Ph+ ALL与慢粒急淋变具有不同的临床特点及治疗反应.%Objective To explore the clinical features of patients with Philadelphia chromosome - positive acute lymphoblastic leukemia (Ph+ ALL) and with chronic myeloid leukemia in lymphoid blast crisis (CML LBC). Methods Retrospective analysis of the clinical data of 21 cases of Ph+ ALL and 31 cases of CML LBC. Results Comparing with Ph+ ALL patients, CML LBC patients showed following clinical features: ① The incidence of splenomegaly and hepatomegaly (80. 65% ) was higher than that of Ph+ ALL (14. 28% ) ( P 0.05 ). Conclusions Paitents with Ph+ ALL and CML LBC present with different clinical features and therapeutic response.

  10. Inhibitory Effects of Omacetaxine on Leukemic Stem Cells and BCR-ABL-Induced Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia in Mice

    OpenAIRE

    Chen, Yaoyu; Hu, Yiguo; Michaels, Shawnya; Segal, David; Brown, Dennis; Li, Shaoguang

    2009-01-01

    Omacetaxine mepesuccinate (formerly homoharringtonine) is a molecule with a mechanism of action that is different from tyrosine kinase inhibitors and its activity in chronic myeloid leukemia (CML) seems to be independent of BCR-ABL mutation status. Using BCR-ABL-expressing myelogenous and lymphoid cell lines and mouse models of CML and B cell acute lymphoblastic leukemia (B-ALL) induced by wild type BCR-ABL or T315I mutant-BCR-ABL, we evaluated the inhibitory effects of omacetaxine on CML and...

  11. Research on PR1 specific cytotoxic T lymphocytes of HLA-A0201 positive chronic myelogenous leukemia%HLA-A0201阳性慢性粒细胞白血病PR1特异性细胞毒性T细胞的初步研究

    Institute of Scientific and Technical Information of China (English)

    王玲玲; 许月; 姜扬文

    2015-01-01

    Objective To evaluate the relationship between proportion of PR1 specific cytotoxic T lymphocytes (CTLs) in the peripheral blood and prognosis and curative effect in patients with HLA-A0201 positive chronic myelogenous leukemia (CML),and to discuss whether PR1 peptide could be used as the following immune therapeutic method for patients who had achieved the standard of stop treatment.Methods The soluble HLA-A0201/PR1 tetramer and flow cytometry were applied to determine the proportion and the frequency of PR1 specific CTLs in peripheral blood from 28 HLA-A0201 positive CML patients.The proportions were compared among different phases of patients.The correlations between the proportion of PR1 specific CTLs and clinical parameters were analyzed.Results There was a negative correlation between PR1 specific CTLs and PCR (bcr-abl/abl)Is (r =-0.658,P < 0.001).The frequencies of PR1 specific CTLs at 3-month,6-month,9-month,12-month,2-year,3-year,4-year,5-year,6-year were (0.06±0.02) %,(0.10± 0.02) %,(0.14±0.02) %,(0.16±0.02) %,(0.20±0.03) %,(0.18±0.03) %,(0.18±0.01) %,(0.17±0.05) % and (0.18±0.03) %,respectively.The frequency of PR1 specific CTLs at 3-month,6-month or 9-month was statistically different compared with that of the other time spots (P < 0.05),and there were no statistical differencies among the frequencies at 1-year,2-year,3-year,4-year,5-year,6-year (P > 0.05).For patients treated with IM 400 mg qd,the frequency of PR1 specific CTLs in high-risk group was lower than that in low-risk or intermediate-risk groups.Conclusion PR1 specific CTLs can be detected in patients who achieved good curative effect,and is correlated with tumor burden,which indicates that PR1 specific CTLs may be related to the action of resisting leukemia and provide the evidence for PR1 peptide as a potential immune therapeutic schedule in patients who have achieved stable MR45 and MR50.%目的 探讨PR1特异性细胞毒性T细胞(CTL)与HLA-A0201阳性

  12. Acute Lymphoblastic Leukemia (ALL) (For Parents)

    Science.gov (United States)

    ... of WBC) are produced, a child will develop acute lymphoblastic, or lymphoid, leukemia (ALL). This is the most common type of childhood leukemia, affecting about 75% of kids with this cancer of the blood cells. Kids ... (AML) Chronic Myelogenous Leukemia (CML) Cancer ...

  13. Lenalidomide and Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Ana Pilar González-Rodríguez

    2013-01-01

    Full Text Available Lenalidomide is an oral immunomodulatory drug used in multiple myeloma and myelodysplastic syndrome and most recently it has shown to be effective in the treatment of various lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL and non-Hodgkin lymphoma. The mechanism of action of lenalidomide varies depending on the pathology, and in the case of CLL, it appears to primarily act by restoring the damaged mechanisms of tumour immunosurveillance. This review discusses the potential mechanism of action and efficacy of lenalidomide, alone or in combination, in treatment of CLL and its toxic effects such as tumor lysis syndrome (TLS and tumor flare reaction (TFR, that make its management different from other hematologic malignancies.

  14. Dimethyl sulfoxide inactivates the anticancer effect of cisplatin against human myelogenous leukemia cell lines in in vitro assays

    OpenAIRE

    Rahul Raghavan; Sanith Cheriyamundath; Joseph Madassery

    2015-01-01

    Objectives: To investigate the effect of DMSO on cisplatin induced cytotoxicity (invitro) against K562 (Human mylogenous leukemia) cell line and to study the cisplatin-DMSO adduct formation using UV-spectrophotometer. Materials and methods: Effect of DMSO on the cytotoxicity of cisplatin was studied in K562 (Chronic mylogenous leukemia) cell line by MTT assay. Cisplatin-DMSO adduct formation was studied by continuously monitoring the increase in absorption peaks for 30 minutes using UV-s...

  15. Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders

    Science.gov (United States)

    2016-10-03

    Chronic Kidney Disease; Acute Myeloid Leukemia (AML); Acute Lymphoblastic Leukemia (ALL); Chronic Myelogenous Leukemia (CML); Chronic Lymphocytic Leukemia (CLL); Non-Hodgkin's Lymphoma (NHL); Hodgkin Disease; Multiple Myeloma; Myelodysplastic Syndrome (MDS); Aplastic Anemia; AL Amyloidosis; Diamond Blackfan Anemia; Myelofibrosis; Myeloproliferative Disease; Sickle Cell Anemia; Autoimmune Diseases; Thalassemia

  16. A case of treatment-related myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemotherapy with autologous stem cell transplantation for non-Hodgkin's lymphoma.

    OpenAIRE

    Jang, Geun Doo; Kim, Sang-We; Suh, Cheol Won; Kim, Eun-Kyoung; Bahng, Hye Seung; Jeong, Young Hoon; Park, Il Gwon; Kim, Woo-Kun; Kim, Sang-Hee; Suh, Eul-Ju; Park, Chan-Jeoung; Ji, Hyun-Sook; Lee, Jung-Shin

    2002-01-01

    Treatment-related myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (t-AML) are now well established as complications of cytotoxic chemotherapy. We experienced a 28-yr-old female patient who developed t-MDS/t-AML with characteristic chromosomal abnormalities including 11q23 chromosomal rearrangement following high-dose chemotherapy with autologous stem cell transplantation (ASCT) for non-Hodgkin's lymphoma. The patient was admitted with bulky abdominal masses of B cell lineage n...

  17. Automatic Recognition of Acute Myelogenous Leukemia in Blood Microscopic Images Using K-means Clustering and Support Vector Machine.

    Science.gov (United States)

    Kazemi, Fatemeh; Najafabadi, Tooraj Abbasian; Araabi, Babak Nadjar

    2016-01-01

    Acute myelogenous leukemia (AML) is a subtype of acute leukemia, which is characterized by the accumulation of myeloid blasts in the bone marrow. Careful microscopic examination of stained blood smear or bone marrow aspirate is still the most significant diagnostic methodology for initial AML screening and considered as the first step toward diagnosis. It is time-consuming and due to the elusive nature of the signs and symptoms of AML; wrong diagnosis may occur by pathologists. Therefore, the need for automation of leukemia detection has arisen. In this paper, an automatic technique for identification and detection of AML and its prevalent subtypes, i.e., M2-M5 is presented. At first, microscopic images are acquired from blood smears of patients with AML and normal cases. After applying image preprocessing, color segmentation strategy is applied for segmenting white blood cells from other blood components and then discriminative features, i.e., irregularity, nucleus-cytoplasm ratio, Hausdorff dimension, shape, color, and texture features are extracted from the entire nucleus in the whole images containing multiple nuclei. Images are classified to cancerous and noncancerous images by binary support vector machine (SVM) classifier with 10-fold cross validation technique. Classifier performance is evaluated by three parameters, i.e., sensitivity, specificity, and accuracy. Cancerous images are also classified into their prevalent subtypes by multi-SVM classifier. The results show that the proposed algorithm has achieved an acceptable performance for diagnosis of AML and its common subtypes. Therefore, it can be used as an assistant diagnostic tool for pathologists. PMID:27563575

  18. Automatic Recognition of Acute Myelogenous Leukemia in Blood Microscopic Images Using K-means Clustering and Support Vector Machine.

    Science.gov (United States)

    Kazemi, Fatemeh; Najafabadi, Tooraj Abbasian; Araabi, Babak Nadjar

    2016-01-01

    Acute myelogenous leukemia (AML) is a subtype of acute leukemia, which is characterized by the accumulation of myeloid blasts in the bone marrow. Careful microscopic examination of stained blood smear or bone marrow aspirate is still the most significant diagnostic methodology for initial AML screening and considered as the first step toward diagnosis. It is time-consuming and due to the elusive nature of the signs and symptoms of AML; wrong diagnosis may occur by pathologists. Therefore, the need for automation of leukemia detection has arisen. In this paper, an automatic technique for identification and detection of AML and its prevalent subtypes, i.e., M2-M5 is presented. At first, microscopic images are acquired from blood smears of patients with AML and normal cases. After applying image preprocessing, color segmentation strategy is applied for segmenting white blood cells from other blood components and then discriminative features, i.e., irregularity, nucleus-cytoplasm ratio, Hausdorff dimension, shape, color, and texture features are extracted from the entire nucleus in the whole images containing multiple nuclei. Images are classified to cancerous and noncancerous images by binary support vector machine (SVM) classifier with 10-fold cross validation technique. Classifier performance is evaluated by three parameters, i.e., sensitivity, specificity, and accuracy. Cancerous images are also classified into their prevalent subtypes by multi-SVM classifier. The results show that the proposed algorithm has achieved an acceptable performance for diagnosis of AML and its common subtypes. Therefore, it can be used as an assistant diagnostic tool for pathologists.

  19. Identification of galectin-1 as a novel mediator for chemoresistance in chronic myeloid leukemia cells.

    Science.gov (United States)

    Luo, Wu; Song, Li; Chen, Xi-Lei; Zeng, Xiang-Feng; Wu, Jian-Zhang; Zhu, Cai-Rong; Huang, Tao; Tan, Xiang-Peng; Lin, Xiao-Mian; Yang, Qi; Wang, Ji-Zhong; Li, Xiao-Kun; Wu, Xiao-Ping

    2016-05-01

    Multidrug resistance protein-1 (MDR1) has been proven to be associated with the development of chemoresistance to imatinib (Glivec, STI571) which displays high efficacy in treatment of BCR-ABL-positive chronic myelogenous leukemia (CML). However, the possible mechanisms of MDR1 modulation in the process of the resistance development remain to be defined. Herein, galectin-1 was identified as a candidate modulator of MDR1 by proteomic analysis of a model system of leukemia cell lines with a gradual increase of MDR1 expression and drug resistance. Coincidently, alteration of galectin-1 expression triggers the change of MDR1 expression as well as the resistance to the cytotoxic drugs, suggesting that augment of MDR1 expression engages in galectin-1-mediated chemoresistance. Moreover, we provided the first data showing that NF-κB translocation induced by P38 MAPK activation was responsible for the modulation effect of galectin-1 on MDR1 in the chronic myelogenous leukemia cells. Galectin-1 might be considered as a novel target for combined modality therapy for enhancing the efficacy of CML treatment with imatinib. PMID:27050374

  20. Inheritance of the chronic myeloproliferative neoplasms. A systematic review

    DEFF Research Database (Denmark)

    Ranjan, Ajenthen; Penninga, E; Jelsig, Am;

    2012-01-01

    This systematic review investigated the inheritance of the classical chronic myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and chronic myelogenous leukemia (CML). Sixty-one articles were included and provided 135...

  1. HLA-B17 and the HLA-A1, B17 haplotype in acute myelogenous leukemia.

    Science.gov (United States)

    Heise, E; Parrish, E; Cooper, R

    1979-08-01

    Seventy-nine Caucasians with acute myelogenous leukemia (AML) were genotyped to determine whether AML, the induction of remission or patient survival were associated with particular HLA phenotypes or haplotypes. HLA-B17 and B27 were increased in AML patients over 40 years of age. Combined analysis of four independent studies indicates that HLA-B17 is significantly but weakly associated with AML, relative risk = 1.48 (.01 less than P less than .025). The A1, B17 and Aw24, Bw35 haplotypes occurred more frequently in the AML group as compared to racial and geographic controls (uncorrected P = 0.0068 and 0.0098, respectively Fisher's Exact Test). Induction of remission occurred less frequently in patients with the B17 phenotype as compared to patients lacking this antigen (P = 0.047). Patient survival was associated with remission status (P = 0.002) but was not significantly associated with particular HLA phenotypes or haplotypes. These results indicate that a gene or genes in the HLA-B region of the major histocompatibility complex can influence susceptibility to AML and also the response to chemotherapy.

  2. The venom of the spider Macrothele raveni induces apoptosis in the myelogenous leukemia K562 cell line.

    Science.gov (United States)

    Liu, Zhonghua; Zhao, Yan; Li, Jing; Xu, Shiyan; Liu, Changjun; Zhu, Yanghui; Liang, Songping

    2012-08-01

    Spider venoms are a rich source of bioactive compounds with therapeutic potential. In traditional Chinese medicine, spiders and spider venoms have been used in the treatment of various ailments. In the present study, the venom of the spider Macrothele raveni potently suppressed cell growth in the myelogenous leukemia K562 cell line in a dose and time-dependent manner with an IC(50) of 5.1 μg/mL. The venom also had a low inhibitory effect on human lymphocytes with an IC(50) of approximately 36.4 μg/mL, indicating that the venom is relatively selective for leukemic cells. Venom treated K562 cells showed typical morphological indicators of apoptosis including condensation of nuclei and fragmentation of DNA. Annexin V-FITC and propidium iodide dual staining further demonstrated that the venom had potent apoptogenic activity. Venom treatment induced caspase 3 and caspase 8 activation in K562 cells and promoted PARP cleavage. The present results indicate that the venom of the spider M. raveni potently and selectively suppresses the growth of K562 cells by inducing apoptosis via caspase 3 and caspase 8 mediated signaling pathways.

  3. Obatoclax Mesylate, Vincristine Sulfate, Doxorubicin Hydrochloride, and Dexrazoxane Hydrochloride in Treating Young Patients With Relapsed or Refractory Solid Tumors, Lymphoma, or Leukemia

    Science.gov (United States)

    2014-04-30

    Acute Leukemias of Ambiguous Lineage; Acute Undifferentiated Leukemia; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Small Intestine Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  4. Acute Myelogenous Leukemia without Maturation with a Retinoic Alpha-Receptor Deletion: A Case Report

    Directory of Open Access Journals (Sweden)

    Christopher Trosclair

    2014-06-01

    Full Text Available Acute promyelocytic leukemia (APL is characterized by a t(15;17 which fuses the 17q retinoic acid alpha-receptor sequence to the 15q PML gene sequence. The resulting fusion product plays a role in the development and maintenance of APL, and is very rarely found in other acute myeloid leukemia (AML subtypes. Rare complex APL genomic rearrangements have retinoic acid alpha-receptor sequence deletions. Here we report a retinoic acid alpha-receptor sequence deletion in a case of AML without differentiation. To our knowledge, this is the first example of a retinoic acid alpha-receptor sequence deletion in this AML subtype.

  5. [Esophageal aspergillosis in a patient with acute myelogenous leukemia and febrile neutropenia].

    Science.gov (United States)

    Besa, Santiago; Kattan, Eduardo; Cid, Ximena; Claro, Juan C

    2014-04-01

    Aspergillosis usually compromises the respiratory system, but can also affect others. We report a 46 yo female with acute myeloid leukemia, developed febrile neutropenia and dysphagia. Endoscopy revealed esophageal cytomegalovirus-like ulcers, but biopsies showed Aspergillus spp. It's important to consider aspergillosis in the differential diagnosis of esophageal lesions in high-risk patients.

  6. Do We Know What Causes Chronic Myelomonocytic Leukemia?

    Science.gov (United States)

    ... Topic Can chronic myelomonocytic leukemia be prevented? Do we know what causes chronic myelomonocytic leukemia? Some cases ... the instructions for nearly everything our cells do. We usually look like our parents because they are ...

  7. Do We Know What Causes Chronic Myeloid Leukemia?

    Science.gov (United States)

    ... Topic Can chronic myeloid leukemia be prevented? Do we know what causes chronic myeloid leukemia? Normal human ... genes, the instructions for how our cells function. We look like our parents because they are the ...

  8. Do We Know What Causes Chronic Lymphocytic Leukemia?

    Science.gov (United States)

    ... Topic Can chronic lymphocytic leukemia be prevented? Do we know what causes chronic lymphocytic leukemia? The exact ... genes -- the instructions for how our cells function. We look like our parents because they are the ...

  9. Chronic myeloid leukemia: reminiscences and dreams.

    Science.gov (United States)

    Mughal, Tariq I; Radich, Jerald P; Deininger, Michael W; Apperley, Jane F; Hughes, Timothy P; Harrison, Christine J; Gambacorti-Passerini, Carlo; Saglio, Giuseppe; Cortes, Jorge; Daley, George Q

    2016-05-01

    With the deaths of Janet Rowley and John Goldman in December 2013, the world lost two pioneers in the field of chronic myeloid leukemia. In 1973, Janet Rowley, unraveled the cytogenetic anatomy of the Philadelphia chromosome, which subsequently led to the identification of the BCR-ABL1 fusion gene and its principal pathogenetic role in the development of chronic myeloid leukemia. This work was also of major importance to support the idea that cytogenetic changes were drivers of leukemogenesis. John Goldman originally made seminal contributions to the use of autologous and allogeneic stem cell transplantation from the late 1970s onwards. Then, in collaboration with Brian Druker, he led efforts to develop ABL1 tyrosine kinase inhibitors for the treatment of patients with chronic myeloid leukemia in the late 1990s. He also led the global efforts to develop and harmonize methodology for molecular monitoring, and was an indefatigable organizer of international conferences. These conferences brought together clinicians and scientists, and accelerated the adoption of new therapies. The abundance of praise, tributes and testimonies expressed by many serve to illustrate the indelible impressions these two passionate and affable scholars made on so many people's lives. This tribute provides an outline of the remarkable story of chronic myeloid leukemia, and in writing it, it is clear that the historical triumph of biomedical science over this leukemia cannot be considered without appreciating the work of both Janet Rowley and John Goldman. PMID:27132280

  10. Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia

    Science.gov (United States)

    2014-06-16

    Childhood Acute Promyelocytic Leukemia (M3); Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Juvenile Myelomonocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  11. 内蒙古地区慢性粒细胞白血病患者HLA-DRB1基因多态性的研究%Study the polymorphisms of HLA-DRB1,alleles in patient's with chronic myelogenous leukemia in Inner Mongolia

    Institute of Scientific and Technical Information of China (English)

    贺立新; 云宇光; 崔明玉; 娜琴; 陈阿梅

    2011-01-01

    Objective: To explore the correlation between the HLA - DRB1, alleles and susceptibility to CML leukemia in Inner Mongolia. Methods: HLA -DRB1 alleles polymorphism in CML patient of 39 were examined with flow cytometry- sequence specific oligonucleotide probes ( FlOW - SSOP) methods. 2480 normal subjects in Northern China as control. Results: The frequencies of allele DRB1 * 1001, HLA - DRB1 * 16XX were increased ( P < 0.05). Conclusion: DRB1 * 1001, DRB1 * 16XX alleles may be positive correlated with Leukemia.%目的 为研究内蒙地区汉族人群人类白细胞抗原(human leukocyte antigen,HLA)DRBI基因与CML白血病的相关性.方法 采用Luminex流式技术-序列特异性寡核苷酸探针反向杂交(flow cytometry-sequence specific oligonuele-otide probe,FLOW-SSOP)方法对内蒙地区39例慢性粒细胞白血病chronic myeloid leukemia,CML)患者HLA-DRB1等位基因多态性进行分析,以北方地区健康群体资料作为正常对照.结果 在HLA-DRB1等位基因中,CML白血病组中DRBI*1001,*16XX等位基因频率高于对照组(0.593%,0.603%,P<0.05).结论 DRBI*1001,DRBI*16XX等位基因与CML相关联,可能是易感基因.

  12. Decreased expression of the amplified mdr1 gene in revertants of multidrug-resistant human myelogenous leukemia K562 occurs without loss of amplified DNA.

    OpenAIRE

    Sugimoto, Y.; Roninson, I B; Tsuruo, T.

    1987-01-01

    Amplification and increased expression of the mdr1 gene associated with multidrug resistance in human tumors were found in multidrug-resistant sublines of human myelogenous leukemia K562 selected with vincristine (K562/VCR) or adriamycin (K562/ADM). In two revertant cell lines of K562/ADM, amplification of the mdr1 gene was maintained at the same level as in K562/ADM, but expression of the 4.5-kilobase mdr1 mRNA was greatly decreased, indicating that amplified genes may be inactivated at the ...

  13. Differential effects of peroxisome proliferator-activated receptor agonists on doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells.

    Science.gov (United States)

    Yousefi, B; Samadi, N; Baradaran, B; Rameshknia, V; Shafiei-Irannejad, V; Majidinia, M; Targhaze, N; Zarghami, N

    2015-01-01

    P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in tumor cells is still a main obstacle for the chemotherapeutic treatment of cancers. Therefore, identification of safe and effective MDR reversing compounds with minimal adverse side effects is an important approach in the cancer treatment. Studies show that peroxisome proliferator-activated receptor (PPARs) ligands can inhibit cell growth in many cancers. Here, we investigated the effect of different PPAR agonists include fenofibrate, troglitazone and aleglitazar on doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells. The effects of doxorubicin (DOX) following treatment with PPAR agonists on cell viability were evaluated using MTT assay and the reversal fold (RF) values. Rhodamine123 (Rh123) assays were used to determine P-gp functioning. P-gp mRNA/protein expression was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analysis after incubation with troglitazone and aleglitazar. Our results showed that troglitazone and aleglitazar significantly enhanced the cytotoxicity of DOX and decreased the RF values in K562/DOX cells, however, no such results were found for fenofibrate. Troglitazone and aleglitazar significantly down regulated P-gp expression in K562/DOX cells; in addition, the present study revealed that aleglitazar elevated intracellular accumulation of Rh123in K562/DOX cells as short-term effects, which also contribute to the reversal of MDR. These findings show that troglitazone and especially aleglitazar exhibited potent effects in the reversal of P-gp-mediated MDR, suggesting that these compounds may be effective for combination therapy strategies and circumventing MDR in K562/DOX cells to other conventional chemotherapeutic drugs. PMID:26718439

  14. TREATMENT RECOMMENDATIONS FOR CHRONIC MYELOID LEUKEMIA

    OpenAIRE

    Michele Baccarani; Fausto Castagnetti; Gabriele Gugliotta; Francesca Palandri; Gianantonio Rosti

    2014-01-01

    The first treatment of chronic myeloid leukemia (CML) included spleen x-radiation and conventional drugs, mainly Busulfan and Hydroxyurea. This therapy improved the quality of life during the chronic phase of the disease, without preventing nor significantly delaying the progression towards advanced phases. The introduction of allogeneic stem cell transplantation (alloSCT) marked the first important breakthrough in the evolution of CML treatment, because about 50% of the eligible patients wer...

  15. Treatment Recommendations for Chronic Myeloid Leukemia

    OpenAIRE

    Baccarani, Michele; Castagnetti, Fausto; Gugliotta, Gabriele; Palandri, Francesca; Rosti, Gianantonio

    2014-01-01

    The first treatment of chronic myeloid leukemia (CML) included spleen x-radiation and conventional drugs, mainly Busulfan and Hydroxyurea. This therapy improved the quality of life during the chronic phase of the disease, without preventing nor significantly delaying the progression towards advanced phases. The introduction of allogeneic stem cell transplantation (alloSCT) marked the first important breakthrough in the evolution of CML treatment, because about 50% of the eligible patients wer...

  16. Acquired protein C deficiency in a child with acute myelogenous leukemia, splenic, renal, and intestinal infarction.

    Science.gov (United States)

    Farah, Roula A; Jalkh, Khalil S; Farhat, Hussein Z; Sayad, Paul E; Kadri, Adel M

    2011-03-01

    We report the case of a 6-year-old boy diagnosed with acute promyelocytic leukemia (AML-M3V) when he presented with pallor, abdominal pain, anorexia, and fatigue. Induction chemotherapy was started according to the AML-BFM 98 protocol along with Vesanoid (ATRA, All-trans retinoic acid). On the sixth day of induction, he developed splenic and gallbladder infarcts. Splenectomy and cholecystectomy were performed while chemotherapy induction continued as scheduled. Four days later, he developed ischemic areas in the kidneys and ischemic colitis in the sigmoid colon. Hypercoagulation studies showed severe deficiency of protein C. Tests showed protein C 16% (reference range 70-140%), protein S 87% (reference range 70-140%), antithrombin III 122% (reference range 80-120%), prothrombin time 13.6 s (reference = 11.3), INR (international normalized ratio) 1.21, partial thromboplastin time 33 s (reference = 33), fibrinogen 214 mg/dl, D-dimer 970 μg/ml, factor II 98%, and that antinuclear antibody, antiphospholipid antibodies, mutation for factor II gene (G20210A), and mutation for Arg506 Gln of factor V were all negative (factor V Leiden). There was no evidence of clinical disseminated intravascular coagulation (DIC). He was treated with low molecular weight heparin and did well. He continues to be in complete remission 7 years later with normal protein C levels. Acquired protein C deficiency can occur in a variety of settings and has been reported in acute myelocytic leukemia. However, clinically significant thrombosis in the absence of clinical DIC, such as our case, remains extremely rare.

  17. Investigation on Marking Method for Phenomenon on Regrowth Drug Resistance in Relapsed Acute Myelogenous Leukemia

    Institute of Scientific and Technical Information of China (English)

    CHEN; Yan(

    2001-01-01

    [1]Preisler H D Venugopal P.Regrowth resistance in cancer:why has it been largely ignored.Cell Prolif 1995 28:347[2]Preisler H D Gropal V.Regrowth drug resistance in leukemia and lymphoma:the need for a new system to classify treatmetn failure and for approaches to treatment.LeukRes 1994 18:149[3]陈燕 乐蓓蓓 喻东姣等.急性髓系白血病Bcl-2/Bax比值与细胞生长类型和耐药关系的研究.同济医科大学学报 1998 27(5):341[4]何明生 陈燕 吴裕丹等.DNR荧光直方图诊断白血病细胞耐药的意义.同济医科大学学报 1999 28(1):31[5]Raza A Yasin Z Gande C.A comparison of rate of DNA synthesis in myeloblasts from peripheral blood and bone marrows of patients with acute nonlymphocytic leukemia.Exp Cell Res 1988 176:13[6]Boise L H Gonzalez-Garcia M Postema C E et al.Bcl&127;X a bcl-2- related gene that functions as a dominant regulator of apoptotic cell death.Cell 1993 74:597[7]杨天楹.急性白血病疗效标准.见:张之南主编.血液病诊断及疗效标准.第2版.北京:科学出版社 1998.214---228[8]Estey E H.Regrowth resistance.Leuk Res 1994 18:161[9]蒋大宗 张文修编.数值诊断的统计方法.西安:陕西科学技术出版社 1981.174-176[10].Smyth M J Krasovskis E Sutton V R et al.The drug efflux protein P-glycoprotein additionally protects drugresistant tumor cells from multiple forms of caspase-dependent apoptosis.Proc Natl Acad Sci USA 1998 95:7024

  18. Therapeutic potential of MEK inhibition in acute myelogenous leukemia: rationale for "vertical" and "lateral" combination strategies.

    Science.gov (United States)

    Ricciardi, Maria Rosaria; Scerpa, Maria Cristina; Bergamo, Paola; Ciuffreda, Ludovica; Petrucci, Maria Teresa; Chiaretti, Sabina; Tavolaro, Simona; Mascolo, Maria Grazia; Abrams, Stephen L; Steelman, Linda S; Tsao, Twee; Marchetti, Antonio; Konopleva, Marina; Del Bufalo, Donatella; Cognetti, Francesco; Foà, Robin; Andreeff, Michael; McCubrey, James A; Tafuri, Agostino; Milella, Michele

    2012-10-01

    In hematological malignancies, constitutive activation of the RAF/MEK/ERK pathway is frequently observed, conveys a poor prognosis, and constitutes a promising target for therapeutic intervention. Here, we investigated the molecular and functional effects of pharmacological MEK inhibition in cell line models of acute myeloid leukemia (AML) and freshly isolated primary AML samples. The small-molecule, ATP-non-competitive, MEK inhibitor PD0325901 markedly inhibited ERK phosphorylation and growth of several AML cell lines and approximately 70 % of primary AML samples. Growth inhibition was due to G(1)-phase arrest and induction of apoptosis. Transformation by constitutively active upstream pathway elements (HRAS, RAF-1, and MEK) rendered FDC-P1 cells exquisitely prone to PD0325901-induced apoptosis. Gene and protein expression profiling revealed a selective effect of PD0325901 on ERK phosphorylation and compensatory upregulation of the RAF/MEK and AKT/p70( S6K ) kinase modules, potentially mediating resistance to drug-induced growth inhibition. Consequently, in appropriate cellular contexts, both "vertical" (i.e., inhibition of RAF and MEK along the MAPK pathway) and "lateral" (i.e., simultaneous inhibition of the MEK/ERK and mTOR pathways) combination strategies may result in synergistic anti-leukemic effects. Overall, MEK inhibition exerts potent growth inhibitory and proapoptotic activity in preclinical models of AML, particularly in combination with other pathway inhibitors. Deeper understanding of the molecular mechanisms of action of MEK inhibitors will likely translate into more effective targeted strategies for the treatment of AML. PMID:22399013

  19. Granulocyte Colony-stimulating Factor-primed Bone Marrow: An Excellent Stem-cell Source for Transplantation in Acute Myelocytic Leukemia and Chronic Myelocytic Leukemia

    Institute of Scientific and Technical Information of China (English)

    Yuhang Li; Min Jiang; Chen Xu; Jianlin Chen; Botao Li; Jun Wang; Jiangwei Hu

    2015-01-01

    Background:Steady-state bone marrow (SS-BM) and granulocyte colony-stimulating growth factor-primed BM/peripheral blood stem-cell (G-BM/G-PBSC) are the main stem-cell sources used in allogeneic hematopoietic stem-cell transplantation.Here,we evaluated the treatment effects of SS-BM and G-BM/G-PBSC in human leucocyte antigen (HLA)-identical sibling transplantation.Methods:A total of 226 patients (acute myelogenous leukemia-complete remission 1,chronic myelogenous leukemia-chronic phase 1) received SS-BM,G-BM,or G-PBSC from an HLA-identical sibling.Clinical outcomes (graft-versus-host disease [GVHD],overall survival,transplant-related mortality [TRM],and leukemia-free survival [LFS]) were analyzed.Results:When compared to SS-BM,G-BM gave faster recovery time to neutrophil or platelet (P < 0.05).Incidence of grade Ⅲ-Ⅳ acute GVHD and extensive chronic GVHD (cGVHD) was lower than seen with SS-BM (P < 0.05) and similar to G-PBSC.Although the incidence of cGVHD in the G-BM group was similar to SS-BM,both were lower than G-PBSC (P < 0.05).G-BM and G-PBSC exhibited similar survival,LFS,and TRM,but were significantly different from SS-BM (P < 0.05).There were no significant differences in leukemia relapse rates among the groups (P > 0.05).Conclusions:G-CSF-primed bone marrow shared the advantages of G-PBSC and SS-BM.We conclude that G-BM is an excellent stem-cell source that may be preferable to G-PBSC or SS-BM in patients receiving HLA-identical sibling hematopoietic stem-cell transplantation.

  20. Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2015-11-10

    Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  1. Treatment Options for Childhood Acute Myeloid Leukemia, Childhood Chronic Myelogenous Leukemia, Juvenile Myelomonocytic ...

    Science.gov (United States)

    ... time, MDS may become AML. Transient myeloproliferative disorder (TMD) is a type of MDS. This disorder of ... of life. Infants who have Down syndrome and TMD have an increased chance of developing AML before ...

  2. Ibrutinib (PCI-32765) in Chronic Lymphocytic Leukemia

    OpenAIRE

    Jain, Nitin; O’Brien, Susan

    2013-01-01

    B-cell receptor (BCR) signaling is essential for chronic lymphocytic leukemia (CLL) cell survival. Many kinases in the BCR signaling pathway are currently being studied as potential therapeutic targets. These include Lyn, Syk, PI3 and Bruton tyrosine (BTK). Ibrutinib (PCI-32765) is a novel first-in-class selective inhibitor of BTK. Preclinical evidence suggests that ibrutinib inhibits CLL cell survival and proliferation. In addition, it also affects CLL cell migration and homing. Early clinic...

  3. A family inheriting different subtypes of acute myelogenous leukemia identifies a gene common to the differentation of multiple hematopoetic lineages and acting early in leukemogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Horwitz, M.S.; Radich, J. [Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Sabath, D.E. [Univ. of Washington, Seattle (United States)

    1994-09-01

    The initial steps promoting carcinogenesis in the hematologic malignancies remain poorly understood. We report on a family with an incompletely penetrant, autosomal dominant syndrome of acute myelogenous leukemia, affecting at least eight adults from three generations. The affected individuals have developed leukemias differing in morphologic subtype, tumor cytogenetics, and abruptness of presentation. Within this family are found subtypes affecting the granulocytic, monocytic, and megakaryocytic lineages. At least one individual has a normal tumor karyotype while another has complex rearrangements including monsomy 7, trisomy 8 and translocation 1;7. Some have presented with acute onset and others with a protracted myelodysplasia syndrome. One person at fifty percent risk of inheriting this gene developed disseminated atypical mycobacterium infection in the absence of leukemia, but also without apparent causes for acquired deficiencies in cellular immunity. Features common to affected family members, including the individual with mycobacterium infection, are the early presence in bone marrow of red cell and platelet maturation defects. A search for mutations in diseased marrows fails to detect abnormalities of p53 exons 5, 6, 7 and 8 or N-ras codons 12, 13 and 61. We conclude that there is a gene in this family that probably acts early in hematopoetic differentiation and confers susceptibility to a wide range of leukemia subtypes spanning the maturation of the myeloid series.

  4. Increased financial burden among patients with chronic myelogenous leukaemia receiving imatinib in Japan: a retrospective survey

    Directory of Open Access Journals (Sweden)

    Kodama Yuko

    2012-04-01

    Full Text Available Abstract Background The financial burden of medical expenses has been increasing for cancer patients. We investigated the relationship between household income and financial burden among patients with chronic myelogenous leukaemia (CML who have been treated with imatinib. Methods A questionnaire was distributed to 1200 patients between May and August 2009. We retrospectively surveyed their household incomes, out-of-pocket medical expenses, final co-payments after refunds, and the perceived financial burden of their medical expenses in 2000, 2005 and 2008. Results A total of 577 patients completed the questionnaire. Their median age was 61 years (range, 15–94. A financial burden was felt by 41.2 % (28 of 68 of the patients treated with imatinib in 2000, 70.8 % (201 of 284 in 2005, and 75.8 % (400 of 528 in 2008. Overall, 182 patients (31.7 % considered its discontinuation because of the financial burden and 15 (2.6 % temporarily stopped their imatinib prescription. In 2000, 2005 and 2008, the patients’ median annual household incomes were 49,615 US Dollars (USD, 38,510 USD and 36,731 USD, respectively, with an average currency exchange rate of 104 Yen/USD in 2008. Their median annual out-of-pocket expenses were 11,548, 12,067 and 11,538 USD and their median final annual co-payments were 4,375, 4,327 and 3,558 USD, respectively. Older patients (OR = 0.96, 95 % CI: 0.95–0.98, p ≪ 0.0001 for 1-year increments, and patients with higher household incomes (OR = 0.92, 95 % CI: 0.85–0.99, p = 0.03 for 10,000 USD-increments were less likely to have considered discontinuing their imatinib treatment. Conversely, patients with higher annual final co-payments (OR = 2.21, 95 % CI: 1.28–4.28, p = 0.004 for 10,000 USD-increments were more likely to have considered discontinuing their imatinib treatment. Conclusions The proportion of CML patients who sensed a financial burden increased between 2000 and 2008

  5. [Treatment of patients with chronic lymphocytic leukemia].

    Science.gov (United States)

    Mucsi, Orsolya

    2016-06-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western countries. The abnormal B lymphocytes progress into the blood and infiltrate the bone marrow, liver, spleen and lymph nodes. CLL is a disease of the adults and older individuals who often have coexisting conditions. It usually progresses slowly, but in patients who need treatment, CLL eventually returns. For relapsed, refractory patients treatment options are limited. The only curative treatment is bone marrow transplantation. However, the new, alternative therapeutics show superior efficacy in CLL than standard regimens. The aim of this review is to summarize the most important therapeutic aspects of CLL and to give an insight into the novel treatment options. PMID:27275639

  6. Stability Analysis of a Simplified Yet Complete Model for Chronic Myelegenous Leukemia

    CERN Document Server

    Jauffret, Marie Doumic; Perthame, Benoît

    2009-01-01

    We analyze the asymptotic behavior of a partial differential equation (PDE) model for hematopoiesis. This PDE model is derived from the original agent-based model formulated by (Roeder et al., Nat. Med., 2006), and it describes the progression of blood cell development from the stem cell to the terminally differentiated state. To conduct our analysis, we start with the PDE model of (Kim et al, JTB, 2007), which coincides very well with the simulation results obtained by Roeder et al. We simplify the PDE model to make it amenable to analysis and justify our approximations using numerical simulations. An analysis of the simplified PDE model proves to exhibit very similar properties to those of the original agent-based model, even if for slightly different parameters. Hence, the simplified model is of value in understanding the dynamics of hematopoiesis and of chronic myelogenous leukemia, and it presents the advantage of having fewer parameters, which makes comparison with both experimental data and alternative...

  7. Establishment of a new cell line (MTT-95 showing basophilic differentiation from the bone marrow of a patient with acute myelogenous leukemia (M7.

    Directory of Open Access Journals (Sweden)

    Mizobuchi N

    1999-04-01

    Full Text Available A new myeloid cell line, MTT-95, was established from the bone marrow of a patient with acute myelogenous leukemia (AML, M7. MTT-95 cells differentiate into mature basophilic cells in culture medium with no chemical component or cytokine. Surface phenotypes were as follows: CD11b 79.3%, CD13 92.4%, CD33 99.8%, CD34 87.9%, CD41a 77.6% and HLA-DR 0.3%. MTT-95 cells were strongly positive for glycoprotein IIb/IIIa by immunohistochemical staining and revealed metachromatic granules. MTT-95 cells seem to possess characteristics of both megakaryocytes and basophils. These findings suggest that MTT-95 cells are basophil progenitors. MTT-95 cells might be useful in the study not only of the biological aspects of basophils, but also of the diversities of AML (M7.

  8. Evolution of ibrutinib resistance in chronic lymphocytic leukemia (CLL)

    OpenAIRE

    Komarova, Natalia L.; Burger, Jan A.; Wodarz, Dominik

    2014-01-01

    Chronic ymphocytic leukemia is the most common leukemia, mostly arising in patients over the age of 50. The disease has been treated with chemo-immunotherapies with varying outcomes, depending on the genetic make-up of the tumor cells. Recently, a promising new tyrosine kinase inhibitor, ibrutinib, has been developed, which resulted in successful responses in clinical trials, even for the most aggressive chronic lymphocytic leukemia types. The crucial current questions include how long diseas...

  9. The Experimental and Clinical Study on the Effect of Curcumin on Cell Cycle Proteins and Regulating Proteins of Apoptosis in Acute Myelogenous Leukemia

    Institute of Scientific and Technical Information of China (English)

    陈燕; 吴裕丹; 何静; 陈文娟

    2002-01-01

    Summary: To investigate whether the Bcl-2 gene family is involved in modulating mechanism ofapoptosis and change of cell cycle protein induced by curcumin in acute myeloid leukemia HL-60cell line and primary acute myelogenous leukemic cells, the Bcl-2 family member Mcl-l, Bax andBak and cell cycle proteins including P27kipl, P21wafl, cyclin D3 and pRbp- were selected and their ex-pression detected by SABC immuno-histochemical stain method. The attitude of sub-G1 peak inDNA histogram was determined by FCM. The TUNEL positive cell percentage was identified byterminal deoxynucleotidyl transferase ( TdT )-mediated Biotin dUNP end labeling technique. Itwas found that when HL-60 cells were treated with 25 μmol/L curcumin for 24 h, the expressionlevel of Mcl-1 was down-regulated, but that of Bax and Bak up-regulated time-dependently. Therewas significant difference in the expression level of Mcl-1, Bax and Bak between the curcumin-treated groups and control group (P<0. 05-0. 01). At the same time, curcumin had no effect onprogress of cell cycle in primaty acute myelogenous leukemia at newly diagnosis, but could in-crease the peak of Sub-G1 (P<0. 05), and down-regulate the expression of Mcl-1 and up-regulatethe expression of Bax and Bak with the difference being statistically significant. The expression ofP27kipl, P21wafl and pRbp- were elevated and that of cyclin D3 decreased in the presence of curcumin.These findings suggested that the Bcl-2 gene family indeed participated in the regulatory process ofapoptosisinduced by curcumin in HL-60 cells and AML cells. Curcumin can induce apoptosis ofprimary acute myelogenous leukemic cells and disturb cell cycle progression of HL-60 cells. Themechanism appeared to be mediated by perturbing Go/G1 phases checkpoints which associated withup-regulation of P27kipl, P21wafl and pRbp- expression, and down-regulation of cyclin D3.

  10. Nilotinib for the treatment of chronic myeloid leukemia: An evidence-based review

    Directory of Open Access Journals (Sweden)

    Elias Jabbour

    2009-10-01

    Full Text Available Elias Jabbour, Jorge Cortes, Hagop KantarjianDepartment of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USAIntroduction: Chronic myelogenous leukemia (CML is a progressive and often fatal hematopoietic neoplasm. The Bcr-Abl tyrosine kinase inhibitor imatinib mesylate represented a major therapeutic advance over conventional CML therapy, with more than 90% of patients obtaining complete hematologic response, and 70%–80% of patients achieving a complete cytogenetic response. Despite the high efficacy of imatinib, a minority of patients in chronic phase CML and more patients in advanced phases are resistant to imatinib, or develop resistance during treatment. This is attributed, in 40% to 50% of cases, to the development of mutations in the Bcr-Abl tyrosine kinase domain that impair imatinib binding. Attempts to circumvent resistance led to the discovery of nilotinib (Tasigna, a novel, potent and selective oral Bcr-Abl kinase inhibitor.Aims: To review the evidence for the use of nilotinib in the management of CML.Evidence review: Preclinical and clinical investigations demonstrate that nilotinib effectively overcomes imatinib resistance, and has further improved the treatment of CML.Place in therapy: Nilotinib is currently indicated for patients with CML in chronic and accelerated phases following imatinib failure. Randomized studies are ongoing to assess the efficacy of nilotinib in patients with newly diagnosed CML.Keywords: CML, tyrosine kinase inhibitors, nilotinib, imatinib-resistance, imatinibintolerance.

  11. The molecular basis of familial chronic lymphocytic leukemia

    OpenAIRE

    Crowther-Swanepoel, Dalemari; Houlston, Richard S.

    2009-01-01

    Our understanding of the genetic basis of chronic lymphocytic leukemia is only just starting to be recognized. This perspective article by Drs. Crowther-Swanepoel and Houlston provides an up-to-date review the molecular epidemiology of chronic lymphocytic leukemia, with emphasis on the integration of biology and genomics. See related paper on page 647.

  12. Induction of Chronic Myeloid Leukemia in Mice.

    Science.gov (United States)

    Zhang, Haojian; Li, Shaoguang

    2016-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder derived from a hematopoietic stem cell (HSC), harboring Philadelphia chromosome (Ph chromosome). Formation of the Ph chromosome is caused by a reciprocal translocation between the chromosomes 9 and 22 t(9;22)(q34;q11), resulting in a fusion protein known as BCR-ABL which has constitutive tyrosine kinase activity and promotes the proliferation of leukemia cells via multiple mechanisms. Studies on CML have led to the identification of the first cancer-associated chromosomal abnormality and the subsequent development of tyrosine kinase inhibitors (TKIs) that inhibit BCR-ABL kinase activity in CML. It has become clear that leukemia stem cells (LSCs) in CML are insensitive to inhibition by TKIs, and eradication of LSCs appears to be difficult. Therefore, some of the major issues in current CML therapy are to understand the biology of LSCs and to investigate why LSCs are insensitive to TKIs for developing curative therapeutic strategies. In this regard, application of mouse models recapitulating human CML disease will be critical. In this chapter, we describe methods for induction of CML in mice with BCR-ABL. PMID:27581135

  13. ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Luca Laurenti

    2010-08-01

    Full Text Available Even if Chronic lymphocytic leukemia (CLL often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment. Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM rates of 38-50%: A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT has been the introduction of non-myeloablative or reduced intensity conditioning (RIC regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL activity. The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients. Sensitive minimal residual disease (MRD quantification has strong prognostic impact after transplant.

  14. Veliparib and Topotecan With or Without Carboplatin in Treating Patients With Relapsed or Refractory Acute Leukemia, High-Risk Myelodysplasia, or Aggressive Myeloproliferative Disorders

    Science.gov (United States)

    2016-04-05

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Hematopoietic and Lymphoid Cell Neoplasm; Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Myelodysplastic Syndrome

  15. Leukemia.

    Science.gov (United States)

    Juliusson, Gunnar; Hough, Rachael

    2016-01-01

    Leukemias are a group of life threatening malignant disorders of the blood and bone marrow. In the adolescent and young adult (AYA) population, the acute leukemias are most prevalent, with chronic myeloid leukemia being infrequently seen. Factors associated with more aggressive disease biology tend to increase in frequency with increasing age, whilst tolerability of treatment strategies decreases. There are also challenges regarding the effective delivery of therapy specific to the AYA group, consequences on the unique psychosocial needs of this age group, including compliance. This chapter reviews the current status of epidemiology, pathophysiology, treatment strategies and outcomes of AYA leukemia, with a focus on acute lymphoblastic leukemia and acute myeloid leukemia. PMID:27595359

  16. Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

    Science.gov (United States)

    2013-06-03

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  17. Clofarabine in combination with a standard remission induction regimen (cytosine arabinoside and idarubicin) in patients with previously untreated intermediate and bad-risk acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): phase I results of an ongoing phase I/II study of the leukemia groups of EORTC and GIMEMA (EORTC GIMEMA 06061/AML-14A trial)

    NARCIS (Netherlands)

    Willemze, R.; Suciu, S.; Muus, P.; Halkes, C.J.; Meloni, G.; Meert, L.; Karrasch, M.; Rapion, J.; Vignetti, M.; Amadori, S.; Witte, T.J.M. de; Marie, J.P.

    2014-01-01

    This study aims to determine the maximum tolerated dose (MTD) of clofarabine combined with the EORTC-GIMEMA 3 + 10 induction regimen (idarubicin + cytosine arabinoside) in adults with untreated acute myelogenous leukemia or high-risk myelodysplastic syndrome. In this phase I trial, 25 patients (medi

  18. Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Giovanni D'Arena

    2013-01-01

    Full Text Available The clinical course of chronic lymphocytic leukemia (CLL may be complicated at any time by autoimmune phenomena.The most common ones are hematologic disorders, such as autoimmune hemolytic anemia (AIHA and immune thrombocytopenia (ITP. Pure red cell aplasia (PRCA and autoimmune agranulocytosis (AG are, indeed, more rarely seen. However, they are probably underestimated due to the possible misleading presence of cytopenias secondary to leukemic bone marrow involvement or to chemotherapy cytotoxicity. The source of autoantibodies is still uncertain, despite the most convincing data are in favor of the involvement of resting normal B-cells. In general, excluding the specific treatment of underlying CLL, the managementof these complications is not different from that of idiopathic autoimmune cytopenias or of those associated to other causes. Among different therapeutic approaches, monoclonal antibody rituximab, given alone or in combination, has shown to be very effective.

  19. Membranoproliferative glomerulonephritis secondary to chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Subramanian Murali

    2010-01-01

    Full Text Available The nephrotic syndrome (NS is a well documented complication of hematological malignancies. However, chronic myeloid leukemia (CML is rarely complicated by the NS, and it occurs usually after allogenic stem cell transplantation or interferon alpha therapy for CML. The NS as a complication of untreated CML is also rare. We report a 31-year-old patient who pre-sented with features of The NS. He was diagnosed to have CML one year ago and was on irre-gular treatment with imatinib mesylate. The renal biopsy and immunofluorescence revealed mem-branoproliferative glomerulonephritis type I. The patient was retreated with imatinib mesylate and the NS resolved gradually over three months. This maybe the third case in literature of mem-branoproliferative glomerulonephritis associated with CML.

  20. Chronic lymphocytic leukemia: concepts and observations

    Energy Technology Data Exchange (ETDEWEB)

    Chandra, P.; Chanana, A.D.; Chikkappa, G.; Cronkite, E.P.

    1977-01-01

    Thirty-five patients with chronic lymphocytic leukemia (CLL) were studied for assessment of total body leukemic mass and abnormality in T-lymphocyte function associated with clinical stages of CLL. Total body potassium (TBK), an indicator of lean body mass, was found to correlate well with increase in the clinical stage of the disease. Use of TBK for monitoring the regression and relapse of leukemic load is suggested. No correlation was found between whole cell and nuclear volumes of lymphocytes in CLL patients and clinical stages of the disease. Blast transformation and proliferation under phytohemagglutinin (PHA) stimulation appeared to be normal in purified T cells of early stages and abnormal in the late stages of disease.

  1. Chronic myeloid leukemia data from India

    Directory of Open Access Journals (Sweden)

    Shweta Bansal

    2013-01-01

    Full Text Available In an effort to collaborate the data of chronic myeloid leukemia (CML patient from all over India,meeting was conceived by ICON ( Indian Cooperative Oncology Network in 2010. This article presents the summarized picture of the data presented in the meeting. In the meeting 8115 patients data was presented and 18 centres submitted their manuscripts comprising of 6677 patients. This data represents large series of patients from all over the country treated on day to day clinical practice and presents the actual outcomes of CML patients in India. The compilation of data confirms the younger age at presentation, increased incidence of resistance and poor outcomes in patients with late chronic phase. It also addresses the issues like Glivec versus Generic drug outcomes, safety of Imatinib during pregnancy and mutational analysis among resistant patients. It concludes that survival and quality of life of CML patients in India has improved over the years especially when treated in early chronic phase. The generic drug is a good option where original is unable to reach the patient due to various reasons. Hopefully, this effort will provide a platform to conduct systematic studies in learning the best treatment options among CML patients in Indian settings.

  2. Stromal control of chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Seke Etet PF

    2013-09-01

    Full Text Available Paul Faustin Seke Etet,1 Armel Herve Nwabo Kamdje,2 Jeremie Mbo Amvene,2 Yousef Aldebasi,3 Mohammed Farahna,1 Lorella Vecchio41Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia; 2Department of Medicine, University of Ngaoundere, Ngaoundere, Cameroon; 3Department of Optometry, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia; 4Laboratory of Cytometry, Institute of Molecular Genetics, CNR, University of Pavia, Pavia, ItalyAbstract: In the ongoing efforts to develop therapies against chronic lymphocytic leukemia (CLL, stromal factors allowing malignant cells to escape spontaneous and chemotherapy-mediated apoptosis, giving way to relapses, have been abundantly investigated. Bone marrow adherent cell types, collectively referred to as stromal cells, appear to be key players in such escape, mainly because CLL malignant cells, which rapidly undergo spontaneous apoptosis when cultured in vitro, survive, migrate, and resist cytotoxic agents in co-culture with bone marrow stromal cells. CLL displays variable clinical courses according to well-defined prognostic factors induced on malignant B-cells (CLL cells or expressed by the transformed bone marrow stromal microenvironment. Particularly, a critical pathogenic role is played by proinflammatory factors, adhesion molecules, and signaling molecules involved in cell fate and stemness, such as Notch, Wnt, sonic Hedgehog, phosphoinositide 3-kinase (PI3K, protein kinase B (Akt, and the B-cell CLL/lymphoma 2 (Bcl-2 family of regulator proteins. As herein discussed, these molecules probably form a complex network favoring CLL cell survival, proliferation, and chemoresistance to anticancer therapy. Characterizing the sets of signaling pathways involved in the interactions between stromal cells and CLL cells may provide new tools for CLL clinical phenotyping and for re-sensitizing chemotherapy resistant cells

  3. ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Patrizia Chiusolo

    2010-05-01

    Full Text Available

    Even if Chronic lymphocytic leukemia (CLL often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment.

    Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM rates of 38-50%:

    A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT has been the introduction of non-myeloablative or reduced intensity conditioning (RIC regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL activity.

    The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients.

    Sensitive minimal residual disease (MRD quantification has strong prognostic impact after transplant.

     

  4. Prognostic significance of serum immunoglobulin pareprotein in chronic lymphocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    杨舒

    2012-01-01

    Objective To investigate the incidence of serum immunoglobulin (Ig) paraprotein in chronic lymphocytic leukemia(CLL) ,and to explore its clinical associated laboratory features and prognostic implication. Methods Serum protein electrophoresis and immunofixation

  5. INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    AnnaMaria Nosari

    2012-01-01

    Full Text Available

    Infectious complications have been known to be a major cause of morbidity and mortality in CLL patients who are predisposed to infections because of both the humoral immunodepression inherent to hematologic disease, which is related to stage and duration of CLL, and to further immunosuppression related to therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The following introduction of monoclonal antibody therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles.

    Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.

  6. INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    AnnaMaria Nosari

    2012-11-01

    Full Text Available Infectious complications have been known to be a major cause of morbidity and mortality in CLL patients who are predisposed to infections because of both the humoral immunodepression inherent to hematologic disease, which is related to stage and duration of CLL, and to further immunosuppression related to therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The following introduction of monoclonal antibody therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles. Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.

  7. Vorinostat, Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2016-05-04

    Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  8. CELL RESPIRATION STUDIES : II. A COMPARATIVE STUDY OF THE OXYGEN CONSUMPTION OF BLOOD FROM NORMAL INDIVIDUALS AND PATIENTS WITH INCREASED LEUCOCYTE COUNTS (SEPSIS; CHRONIC MYELOGENOUS LEUCEMIA).

    Science.gov (United States)

    Daland, G A; Isaacs, R

    1927-06-30

    1. The oxygen consumption of blood of normal individuals, when the hemoglobin is saturated with oxygen, is practically zero within the limits of experimental error of the microspirometer used. 2. The oxygen consumed in a microspirometer by the blood of patients with chronic myelogenous leucemia with a high white blood cell count, and of one with leucocytosis from sepsis, was proportional to the number of adult polymorphonuclear neutrophils in the blood. 3. No correlation could be made between the rate of oxygen absorption and the total number of white blood cells in the blood, or the total number of immature cells, or the number of red blood cells, or the amount of oxyhemoglobin. 4. The blood of patients with chronic myelogenous leucemia continued to use oxygen in the microspirometer longer than that of normal individuals, and the hemoglobin, in the leucemic bloods, became desaturated even though exposed to air. 5. In blood in which the bulk. of the cells were immature and the mature cells few, the oxygen consumption was lower than in blood in which the mature cells predominated. The rate of oxygen consumption of the immature cells was relatively low as compared to the mature. 6. The slower rate of oxygen absorption by the immature leucocytes in chronic myelogenous leucemia as compared to the mature cells, places them, in accord with Warburg's reports, in the class of the malignant tissues in this respect rather than in the group of young or embryonic cells.

  9. Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia

    Science.gov (United States)

    Vener, Tatiana I.; Raponi, Mitch; Ritchie, Ellen K.; Smith, B. Douglas; Gore, Steven D.; Morris, Lawrence E.; Feldman, Eric J.; Greer, Jacqueline M.; Malek, Sami; Carraway, Hetty E.; Ironside, Valerie; Galkin, Steven; Levis, Mark J.; McDevitt, Michael A.; Roboz, Gail R.; Gocke, Christopher D.; Derecho, Carlo; Palma, John; Wang, Yixin; Kaufmann, Scott H.; Wright, John J.; Garret-Mayer, Elizabeth

    2012-01-01

    Tipifarnib (T) exhibits modest activity in elderly adults with newly diagnosed acute myelogenous leukemia (AML). Based on preclinical synergy, a phase 1 trial of T plus etoposide (E) yielded 25% complete remission (CR). We selected 2 comparable dose levels for a randomized phase 2 trial in 84 adults (age range, 70-90 years; median, 76 years) who were not candidates for conventional chemotherapy. Arm A (T 600 mg twice a day × 14 days, E 100 mg days 1-3 and 8-10) and arm B (T 400 mg twice a day × 14 days, E 200 mg days 1-3 and 8-10) yielded similar CR, but arm B had greater toxicity. Total CR was 25%, day 30 death rate 7%. A 2-gene signature of high RASGRP1 and low aprataxin (APTX) expression previously predicted for T response. Assays using blasts from a subset of 40 patients treated with T plus E on this study showed that AMLs with a RASGRP1/APTX ratio of more than 5.2 had a 78% CR rate and negative predictive value 87%. This ratio did not correlate with outcome in 41 patients treated with conventional chemotherapies. The next T-based clinical trials will test the ability of the 2-gene signature to enrich for T responders prospectively. This study is registered at www.clinicaltrials.gov as #NCT00602771. PMID:22001391

  10. Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia.

    Science.gov (United States)

    Karp, Judith E; Vener, Tatiana I; Raponi, Mitch; Ritchie, Ellen K; Smith, B Douglas; Gore, Steven D; Morris, Lawrence E; Feldman, Eric J; Greer, Jacqueline M; Malek, Sami; Carraway, Hetty E; Ironside, Valerie; Galkin, Steven; Levis, Mark J; McDevitt, Michael A; Roboz, Gail R; Gocke, Christopher D; Derecho, Carlo; Palma, John; Wang, Yixin; Kaufmann, Scott H; Wright, John J; Garret-Mayer, Elizabeth

    2012-01-01

    Tipifarnib (T) exhibits modest activity in elderly adults with newly diagnosed acute myelogenous leukemia (AML). Based on preclinical synergy, a phase 1 trial of T plus etoposide (E) yielded 25% complete remission (CR). We selected 2 comparable dose levels for a randomized phase 2 trial in 84 adults (age range, 70-90 years; median, 76 years) who were not candidates for conventional chemotherapy. Arm A (T 600 mg twice a day × 14 days, E 100 mg days 1-3 and 8-10) and arm B (T 400 mg twice a day × 14 days, E 200 mg days 1-3 and 8-10) yielded similar CR, but arm B had greater toxicity. Total CR was 25%, day 30 death rate 7%. A 2-gene signature of high RASGRP1 and low aprataxin (APTX) expression previously predicted for T response. Assays using blasts from a subset of 40 patients treated with T plus E on this study showed that AMLs with a RASGRP1/APTX ratio of more than 5.2 had a 78% CR rate and negative predictive value 87%. This ratio did not correlate with outcome in 41 patients treated with conventional chemotherapies. The next T-based clinical trials will test the ability of the 2-gene signature to enrich for T responders prospectively. This study is registered at www.clinicaltrials.gov as #NCT00602771.

  11. A role for BMP-induced homeobox gene MIXL1 in acute myelogenous leukemia and identification of type I BMP receptor as a potential target for therapy.

    Science.gov (United States)

    Raymond, Aaron; Liu, Bin; Liang, Hong; Wei, Caimiao; Guindani, Michele; Lu, Yue; Liang, Shoudan; St John, Lisa S; Molldrem, Jeff; Nagarajan, Lalitha

    2014-12-30

    Mesoderm Inducer in Xenopus Like1 (MIXL1), a paired-type homeobox transcription factor induced by TGF-β family of ligands is required for early embryonic specification of mesoderm and endoderm. Retrovirally transduced Mixl1 is reported to induce acute myelogenous leukemia (AML) with a high penetrance. But the mechanistic underpinnings of MIXL1 mediated leukemogenesis are unknown. Here, we establish the protooncogene c-REL to be a transcriptional target of MIXL1 by genome wide chromatin immune precipitation. Accordingly, expression of c-REL and its downstream targets BCL2L1 and BCL2A2 are elevated in MIXL1 expressing cells. Notably, MIXL1 regulates c-REL through a zinc finger binding motif, potentially by a MIXL1-Zinc finger protein transcriptional complex. Furthermore, MIXL1 expression is detected in the cancer genome atlas (TCGA) AML samples in a pattern mutually exclusive from that of HOXA9, CDX2 and HLX suggesting the existence of a core, yet distinct HOX transcriptional program. Finally, we demonstrate MIXL1 to be induced by BMP4 and not TGF-β in primary human hematopoietic stem and progenitor cells. Consequently, MIXL1 expressing AML cells are preferentially sensitive to the BMPR1 kinase inhibitor LDN-193189. These findings support the existence of a novel MIXL1-c REL mediated survival axis in AML that can be targeted by BMPR1 inhibitors. (MIXL1- human gene, Mixl1- mouse ortholog, MIXL1- protein). PMID:25544748

  12. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Saglio, Giuseppe; Kim, Dong-Wook; Issaragrisil, Surapol;

    2010-01-01

    Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase.......Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase....

  13. 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

  14. Isochromosome 17q in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Eyad Alhourani

    2015-01-01

    Full Text Available In chronic lymphocytic leukemia (CLL, presence of acquired cytogenetic abnormalities may help to estimate prognosis. However, deletion of TP53 gene, which is associated with an aggressive course of the disease and poor prognosis along with a lack of response to treatment, is one of the alterations which may escape cytogenetic diagnoses in CLL. Thus, other techniques have emerged such as interphase fluorescence in situ hybridization (iFISH. Deletion of TP53 may but must not go together with the formation of an isochromosome i(17q; surprisingly this subgroup of patients was not in the focus of CLL studies yet. This study was about if presence of i(17q could be indicative for a new subgroup in CLL with more adverse prognosis. As a result, TP53 deletion was detected in 18 out of 150 (12% here studied CLL cases. Six of those cases (~33% had the TP53 deletion accompanied by an i(17q. Interestingly, the cases with i(17q showed a tendency towards more associated chromosomal aberrations. These findings may be the bases for follow-up studies in CLL patients with TP53 deletion with and without i(17q; it may be suggested that the i(17q presents an even more adverse prognostic marker than TP53 deletion alone.

  15. The lymph node in chronic lymphocytic leukemia.

    Science.gov (United States)

    Dick, F R; Maca, R D

    1978-01-01

    Lymph nodes were examined from 41 cases of typical chronic lymphocytic leukemia (CLL). Degree of immaturity was graded as absent to minimal (Grade I), moderate (Grade II) and marked (Grade III). A moderate degree of immaturity was found in the lymph node in 14 of 41 cases even though the cells seen on the initial bone marrow and peripheral blood smears obtained from these patients were essentially all mature. The morphology of these nodes could be confused with poorly differentiated lymphocytic or mixed lymphocytic-histiocytic lymphoma in terms of the degree of immaturity present. A marked degree of immaturity present. A marked degree of immaturity was found in 5 cases; the morphology of these cases resembled histiocytic lymphoma. In the remaining 22 cases immaturity was essentially absent. The morphology of these cases was similar to that of diffuse well differentiated lymphocytic lymphoma. Our studies suggest that a moderate degree of immaturity in the lymph node of patients with CLL does not indicate that these patients will have a marked shortening of their survival. PMID:580071

  16. TREATMENT RECOMMENDATIONS FOR CHRONIC MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Michele Baccarani

    2014-01-01

    Full Text Available The first treatment of chronic myeloid leukemia (CML included spleen x-radiation and conventional drugs, mainly Busulfan and Hydroxyurea. This therapy improved the quality of life during the chronic phase of the disease, without preventing nor significantly delaying the progression towards advanced phases. The introduction of allogeneic stem cell transplantation (alloSCT marked the first important breakthrough in the evolution of CML treatment, because about 50% of the eligible patients were cured. The second breakthrough was the introduction of human recombinant interferon-alfa, able to achieve a complete cytogenetic remission in 15% to 30% of patients, with a significant survival advantage over conventional chemotherapy. At the end of the last century, about 15 years ago, all these treatments were quickly replaced by a class of small molecules targeting the tyrosine kinases (TK, which were able to induce a major molecular remission in most of the patients, without remarkable side effects, and a very prolonged life-span. The first approved TK inhibitor (TKI was Imatinib Mesylate (Glivec or Gleevec, Novartis. Rapidly, other TKIs were developed tested and commercialized, namely Dasatinib (Sprycel, Bristol-Myers Squibb, Nilotinib (Tasigna, Novartis, Bosutinib (Busulif, Pfizer and Ponatinib (Iclusig, Ariad. Not all these compounds are available worldwide; some of them are approved only for second line treatment, and the high prices are a problem that can limit their use. A frequent update of treatment recommendations is necessary. The current treatment goals include not only the prevention of the transformation to the advanced phases and the prolongation of survival, but also a length of survival and of a quality of life comparable to that of non-leukemic individuals. In some patient the next ambitious step is to move towards a treatment-free remission. The CML therapy, the role of alloSCT and the promising experimental strategies are reviewed in

  17. Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2016-02-16

    Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

  18. Sarcoma granulocítico multicêntrico como recidiva de leucemia mieloide aguda Multicentric granulocytic sarcoma as relapse of acute myelogenous leukemia

    Directory of Open Access Journals (Sweden)

    Taciana G. S. Aguiar

    2009-01-01

    Full Text Available Sarcoma granulocítico (SG é um tumor sólido extramedular, constituído por células precursoras de granulócitos. É geralmente associado a leucemia mieloide aguda ou raramente a outras desordens mieloproliferativas. O tumor geralmente ocorre precedendo uma leucemia mieloide aguda, durante o seu curso ou após a remissão ter sido alcançada. O prognóstico é pobre e tem como principais modalidades terapêuticas a quimioterapia e a radioterapia. Relata- se um caso de SG multicêntrico, de evolução rápida, com acometimento difuso de pele, mamas, gânglios linfáticos, tecido celular subcutâneo e líquor, em mulher de 45 anos, fora de tratamento para leucemia mieloide aguda e em remissão hematológica há 18 meses. A paciente apresentava dor intensa em membro inferior direito há uma semana e estava em anticoagulação oral há seis meses por trombose venosa profunda neste membro. Diagnosticado o SG, a paciente foi tratada com radioterapia e quimioterapia com boa resposta. Após três meses de seguimento, em vigência do tratamento quimioterápico, evoluiu com recidiva do SG neste membro, associado ao acometimento das mamas e posteriormente do sistema nervoso central, evoluindo para óbito em aplasia e sepses.Granulocytic sarcoma is an extramedullary solid tumor consisting of immature granulocytic cells. It is often associated with acute myelogenous leukemia and more rarely with other myeloproliferative disorders. The tumor generally occurs before acute myeloid leukemia, during its course or after disease remission. It has a poor prognosis with the main therapeutic options being chemotherapy and radiotherapy. A multicentric accelerated case of granulocytic sarcoma of a 45- year- old woman with diffuse skin, breast, lymphatic ganglia and subcutaneous tissue presentations no longer undergoing treatment for acute myeloid leukemia and in hematologic remission for 18 months is reported. The patient presented with severe pain of right lower

  19. Development and targeted use of nilotinib in chronic myeloid leukemia

    OpenAIRE

    Carmen Fava; Hagop Kantarjian; Jorge Cortes; Elias Jabbour

    2009-01-01

    Carmen Fava, Hagop Kantarjian, Jorge Cortes, Elias JabbourDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USAAbstract: The development of imatinib has resulted in sustained hematologic and cytogenetic remissions in all phases of chronic myeloid leukemia (CML). Despite the high efficacy, relapses have been observed and are much more prevalent in patients with advanced disease. The most common mechanism of acquired resistance has been traced to Bcr-Abl...

  20. Development and targeted use of nilotinib in chronic myeloid leukemia

    OpenAIRE

    Jabbour, Elias

    2008-01-01

    Carmen Fava, Hagop Kantarjian, Jorge Cortes, Elias JabbourDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USAAbstract: The development of imatinib has resulted in sustained hematologic and cytogenetic remissions in all phases of chronic myeloid leukemia (CML). Despite the high efficacy, relapses have been observed and are much more prevalent in patients with advanced disease. The most common mechanism of acquired resistance has been traced to Bcr-Abl...

  1. The role of the Philadelphia translocation in chronic myeloid leukemia

    OpenAIRE

    Geurts Van Kessel, Ad

    1983-01-01

    textabstractDuring the last two decades evidence for a close association between the presence of specific chromosomal abnormalities and the occurrence of several types of cancers and leukemias has accumulated. The Philadelphia (Ph 1) translocation, present in about 90% of the patients with chronic myeloid leukemia (CML), is one of the most typical and best documented examples of such an aberration. Usually this translocation involves chromosome 9 and 22: t(9;22)(q34;q11). The translocation pr...

  2. Treatment of Chronic Myelomonocytic Leukemia with 5-Azacytidine: Case Reports

    OpenAIRE

    Peter Rohon; Jana Vondrakova; Anna Jonasova; Milena Holzerova; Marie Jarosova; Karel Indrak

    2012-01-01

    Epigenetic therapy with hypomethylating agent (5-azacytidine; AZA) is common in the management of specific subtypes of myelodysplastic syndrome (MDS), but there are only few studies in chronic myelomonocytic leukemia (CMML) patients. In this paper our experience with 3 CMML patients treated with AZA is described. In one patient transfusion independency was observed after 4 treatment cycles; in one case a partial response was recorded, but a progression to acute myeloid leukemia (AML) after 13...

  3. Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia or Chronic Myeloid Leukemia in Lymphoid Blast Crisis.

    Science.gov (United States)

    Kolenova, Alexandra; Maloney, Kelly W; Hunger, Stephen P

    2016-08-01

    The clinical characteristics of chronic myeloid leukemia (CML) in lymphoid blast crisis (BC) can resemble those of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL). Because of this, there can be concern as to whether a patient with newly diagnosed Ph leukemia has Ph ALL or CML in lymphoid BC. This distinction has significant potential therapeutic implications because most children with Ph ALL are now treated with chemotherapy plus a tyrosine kinase inhibitor, whereas allogeneic stem cell transplant is usually recommended for any patient with CML that presents in or later develops BC. PMID:27164534

  4. Chronic lymphocytic leukemia: case-based session.

    Science.gov (United States)

    Rai, K R; Döhner, H; Keating, M J; Montserrat, E

    2001-01-01

    Drs. Hartmut Döhner, Michael J. Keating, Kanti R. Rai and Emili Montserrat form the panel to review chronic lymphocytic leukemia (CLL) while focusing on the clinical features of a particular patient. The pace of progress in CLL has accelerated in the past decade. The pathophysiological nature of this disease, as had been known in the past, was based largely on the intuitive and empiric notions of two leaders in hematology, William Dameshek and David Galton. Now the works of a new generation of leaders are providing us with the scientific explanations of why CLL is a heterogeneous disease, perhaps consisting of at least two separate entities. In one form of CLL, the leukemic lymphocytes have a surface immunoglobulin (Ig) variable region gene that has undergone somatic mutations, with tell-tale markers suggesting that these cells had previously traversed the germinal centers. Such patients have a distinctly superior prognosis than their counterparts whose leukemic lymphocytes IgV genes have no mutations (these are indeed immunologically naive cells), who have a worse prognosis. The introduction of fluorescence in situ hybridization (FISH) technique has provided us with new insights into the diverse chromosomal abnormalities that can occur in CLL, and which have significant impact on the clinical behavior and prognosis of patients with this disease. Major advances in therapeutics of CLL also have occurred during the past decade. Two monoclonal antibodies, Campath-1H (anti-CD52) and rituximab (anti-CD20), and one nucleoside analogue, fludarabine, have emerged as three agents of most promise in the front-line treatment of this disease. Studies currently in progress reflect our attempts to find the most effective manner of combining these agents to improve the overall survival statistics for CLL patients. As in many other hematological malignancies, high dose chemotherapy followed by autologous or HLA-compatible allogeneic stem cells rescue strategies are under study as

  5. Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Lymphocytic or Myelogenous Leukemia

    Science.gov (United States)

    2016-09-07

    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); Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  6. Prolonged T1 relaxation of the hemopoietic bone marrow in patients with chronic leukemia

    DEFF Research Database (Denmark)

    Jensen, K E; Sørensen, P G; Thomsen, C;

    1990-01-01

    Eleven patients with chronic leukemia (7 with chronic lymphocytic leukemia and 4 with chronic myeloid leukemia) were evaluated with magnetic resonance (MR) imaging and T1 relaxation time measurements by use of a 1.5 tesla whole body MR scanner. Bone marrow biopsies were obtained from the posterior...

  7. Massive ascites as a presenting manifestation of chronic lymphocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    Neelam Siddiqui; Saeed Al-Amoudi; Aamer Aleem; Maha Arafah; Layla Al-Gwaiz

    2008-01-01

    Ascites is not an uncommon manifestation of certain solid tumors like gastrointestinal malignancies, ovarian cancer and breast cancer. However, it is unusual to encounter ascites in patients with hematological malignancies especially chronic leukemia. The patient described here presented with massive ascites and blood lymphocytosis. Further studies confirmed the diagnosis of chronic lymphocytic leukemia with ascites. The ascitic fluid was exudative, consisting of mature-looking B-lymphocytes, which were morphologically and immunophenotypically similar to peripheral blood and bone marrow cells. The patient was treated with chemotherapy and achieved a good response and diminution of ascitic fluid accumulation.

  8. Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML.

    Directory of Open Access Journals (Sweden)

    Young Kwang Chae

    Full Text Available Aquaporins (AQPs have previously been associated with increased expression in solid tumors. However, its expression in hematologic malignancies including CML has not been described yet. Here, we report the expression of AQP5 in CML cells by RT-PCR and immunohistochemistry. While normal bone marrow biopsy samples (n = 5 showed no expression of AQP5, 32% of CML patient samples (n = 41 demonstrated AQP5 expression. In addition, AQP5 expression level increased with the emergence of imatinib mesylate resistance in paired samples (p = 0.047. We have found that the overexpression of AQP5 in K562 cells resulted in increased cell proliferation. In addition, small interfering RNA (siRNA targeting AQP5 reduced the cell proliferation rate in both K562 and LAMA84 CML cells. Moreover, by immunoblotting and flow cytometry, we show that phosphorylation of BCR-ABL1 is increased in AQP5-overexpressing CML cells and decreased in AQP5 siRNA-treated CML cells. Interestingly, caspase9 activity increased in AQP5 siRNA-treated cells. Finally, FISH showed no evidence of AQP5 gene amplification in CML from bone marrow. In summary, we report for the first time that AQP5 is overexpressed in CML cells and plays a role in promoting cell proliferation and inhibiting apoptosis. Furthermore, our findings may provide the basis for a novel CML therapy targeting AQP5.

  9. SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo.

    Science.gov (United States)

    Yang, Li; Weng, Wei; Sun, Zhi-Xin; Fu, Xian-Jie; Ma, Jun; Zhuang, Wen-Fang

    2015-05-15

    Previous studies have identified sphingosine kinase 1 (SphK1) as a potential drug target for treatment of acute myeloid leukemia (AML). In the current study, we investigated the potential anti-leukemic activity of a novel and specific SphK1 inhibitor, SKI-II. We demonstrated that SKI-II inhibited growth and survival of human AML cell lines (HL-60 and U937 cells). SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, and concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells. Conversely, exogenously-added S1P protected against SKI-II-induced cytotoxicity, while cell permeable short-chain ceramide (C6) aggravated SKI-II's lethality against AML cells. Notably, SKI-II induced potent apoptotic death in primary human AML cells, but was generally safe to the human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. In vivo, SKI-II administration suppressed growth of U937 leukemic xenograft tumors in severe combined immunodeficient (SCID) mice. These results suggest that SKI-II might be further investigated as a promising anti-AML agent.

  10. Proteomic profiling identifies distinct protein patterns in acute myelogenous leukemia CD34+CD38- stem-like cells.

    Directory of Open Access Journals (Sweden)

    Steven M Kornblau

    Full Text Available Acute myeloid leukemia (AML is believed to arise from leukemic stem-like cells (LSC making understanding the biological differences between LSC and normal stem cells (HSC or common myeloid progenitors (CMP crucial to understanding AML biology. To determine if protein expression patterns were different in LSC compared to other AML and CD34+ populations, we measured the expression of 121 proteins by Reverse Phase Protein Arrays (RPPA in 5 purified fractions from AML marrow and blood samples: Bulk (CD3/CD19 depleted, CD34-, CD34+(CMP, CD34+CD38+ and CD34+CD38-(LSC. LSC protein expression differed markedly from Bulk (n =31 cases, 93/121 proteins and CD34+ cells (n = 30 cases, 88/121 proteins with 54 proteins being significantly different (31 higher, 23 lower in LSC than in either Bulk or CD34+ cells. Sixty-seven proteins differed significantly between CD34+ and Bulk blasts (n = 69 cases. Protein expression patterns in LSC and CD34+ differed markedly from normal CD34+ cells. LSC were distinct from CD34+ and Bulk cells by principal component and by protein signaling network analysis which confirmed individual protein analysis. Potential targetable submodules in LSC included the proteins PU.1(SP1, P27, Mcl1, HIF1α, cMET, P53, Yap, and phospho-Stats 1, 5 and 6. Protein expression and activation in LSC differs markedly from other blast populations suggesting that studies of AML biology should be performed in LSC.

  11. Cytogenetic evidence for recurrence of acute myelogenous leukemia after allogeneic bone marrow transplantation in donor hematopoietic cells

    Energy Technology Data Exchange (ETDEWEB)

    Elfenbein, G.J.; Brogaonkar, D.S.; Bias, W.B.

    1978-09-01

    A 22-yr-old man with acute myelocytic leukemia received a bone marrow transplant from a genotypically HLA-identical female sibling after cyclophosphamide preparation. He remained in complete remission for 18 mo, when he developed a chloroma in the perineum. The chloroma was treated with local radiotherapy. The chloroma recurred 8 mo later and was treated with radiotherapy followed by combination chemotherapy. At 34 mo after transplant, marrow relapse and chloroma were documented. The first chloroma contained host cells by fluorescent Y-chromatin body analyses of interphase nuclei. All metaphase cells and karyotypes from peripheral blood and marrow samples showed no evidence of host cells from 3 wk after transplant through the time of marrow relapse. Data from autosomal and sex chromosome studies indicate that the marrow relapse occurred in cells of donor origin. A new consistent chromosome abnormality (45, X, -X, t(8;21) (q22; q22)) was observed in a majority of donor cells. The patient received a second bone marrow transplant from the same donor after preparation with busulfan and cyclophosphamide and attained a complete remission with full hematologic engraftment.

  12. The role of the Philadelphia translocation in chronic myeloid leukemia

    NARCIS (Netherlands)

    A.H.M. Geurts van Kessel (Ad)

    1983-01-01

    textabstractDuring the last two decades evidence for a close association between the presence of specific chromosomal abnormalities and the occurrence of several types of cancers and leukemias has accumulated. The Philadelphia (Ph 1) translocation, present in about 90% of the patients with chronic m

  13. Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Herman, S E M; Niemann, C U; Farooqui, M;

    2014-01-01

    Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further...

  14. SRSF2 mutation in patients with chronic myelomonocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    杨向绸

    2014-01-01

    Objective To investigate SRSF2 mutations in patients with chronic myelomonocytic leukemia(CMML)and the clinical characteristics of patients with SRSF2mutants.Methods In this study,the frequency of SRSF2mutation in a cohort of 20 patients with CMML was detected by polymerase chain reaction(PCR)followed by direct

  15. Interferon alpha for treatment of chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Hjorth-Hansen, Henrik; Bjerrum, Ole Weis;

    2011-01-01

    Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-α) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-α compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions...

  16. Interferon alpha for treatment of chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Hjorth-Hansen, Henrik; Bjerrum, Ole Weis;

    2011-01-01

    Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-a) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-a compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions...

  17. BCR-ABL Promotes PTEN Downregulation in Chronic Myeloid Leukemia

    OpenAIRE

    Cristina Panuzzo; Sabrina Crivellaro; Giovanna Carrà; Angelo Guerrasio; Giuseppe Saglio; Alessandro Morotti

    2014-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the t(9;22) translocation coding for the chimeric protein p210 BCR-ABL. The tumor suppressor PTEN plays a critical role in the pathogenesis of CML chronic phase, through non genomic loss of function mechanisms, such as protein down-regulation and impaired nuclear/cytoplasmic shuttling. Here we demonstrate that BCR-ABL promotes PTEN downregulation through a MEK dependent pathway. Furthermore, we describe a novel n...

  18. Clofarabine Plus Cytarabine Compared With Cytarabine Alone in Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia: Results From the CLASSIC I Trial

    Science.gov (United States)

    Faderl, Stefan; Wetzler, Meir; Rizzieri, David; Schiller, Gary; Jagasia, Madan; Stuart, Robert; Ganguly, Siddhartha; Avigan, David; Craig, Michael; Collins, Robert; Maris, Michael; Kovacsovics, Tibor; Goldberg, Stuart; Seiter, Karen; Hari, Parameswaran; Greiner, Jochen; Vey, Norbert; Recher, Christian; Ravandi, Farhad; Wang, Eunice S.; Vasconcelles, Michael; Huebner, Dirk; Kantarjian, Hagop M.

    2012-01-01

    Purpose To compare the receipt of clofarabine plus cytarabine (Clo+Ara-C arm) with cytarabine (Ara-C arm) in patients ≥ 55 years old with refractory or relapsed acute myelogenous leukemia (AML). Patients and Methods Patients were randomly assigned to receive either clofarabine (Clo) 40 mg/m2 or a placebo followed by Ara-C 1 g/m2 for five consecutive days. The primary end point was overall survival (OS). Secondary end points included event-free survival (EFS), 4-month EFS, overall remission rate (ORR; complete remission [CR] plus CR with incomplete peripheral blood count recovery), disease-free survival (DFS), duration of remission (DOR), and safety. Results Among 320 patients with confirmed AML (median age, 67 years), the median OS was 6.6 months in the Clo+Ara-C arm and 6.3 months in the Ara-C arm (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00). The ORR was 46.9% in the Clo+Ara-C arm (35.2% CR) versus 22.9% in the Ara-C arm (17.8% CR; P < .01). EFS (HR: 0.63; 95% CI, 0.49 to 0.80; P < .01) and 4-month EFS (37.7% v 16.6%; P < .01) favored the Clo+Ara-C arm compared with Ara-C arm, respectively. DFS and DOR were similar in both arms. Overall 30-day mortality was 16% and 5% for CLO+Ara-C and Ara-C arms, respectively. In the Clo+Ara-C and Ara-C arms, the most common grade 3 to 4 toxicities were febrile neutropenia (47% v 35%, respectively), hypokalemia (18% v 11%, respectively), thrombocytopenia (16% v 17%, respectively), pneumonia (14% v 10%, respectively), anemia (13% v 0%, respectively), neutropenia (11% v 9%, respectively), increased AST (11% v 2%, respectively), and increased ALT (10% v 3%, respectively). Conclusion Although the primary end point of OS did not differ between arms, Clo+Ara-C significantly improved response rates and EFS. Study follow-up continues, and the role of clofarabine in the treatment of adult patients with AML continues to be investigated. PMID:22585697

  19. Comparison of molecular biology, immunological characteristics and clinical efficacy in patients with acute myelogenous leukemia with or without FLT3-ITD gene mutation

    Directory of Open Access Journals (Sweden)

    Ting-ting LI

    2013-07-01

    Full Text Available Objective To compare the clinical and laboratory characteristics, therapeutic efficacy and prognosis of acute myelogenous leukemia (AML with or without FLT3-ITD gene mutation. Methods The clinical data of 93 AML patients, aged from 10 to 66 years, were retrospectively analyzed. Among them, 21 patients were FLT3-ITD gene (FLT3-ITD+AML group positive, and 72 patients were negative for FLT3-ITD gene (FLT3-ITD-AML group. The patients' chromosomes were examined, and mutation of FLT3-ITD and NPM1 gene and the expressions of HOX11, ETO, EVI and NPM1 gene were analyzed, along with the 2-year event-free survival and 2-year overall survival were learned. Results At primary diagnosis, the proportion of patients with WBC>100×109/L, and bleeding rate was significantly higher in FLT3-ITD+ AML group than that in FLT3-ITD-AML group (P=0.04; P=0.01, but no statistical difference was found in age, immunophenotype and chromosomal abnormality (P>0.05. The complete remission (CR rate was 28.57% in FLT3-ITD+ AML group, and it was obviously lower than that in FLT3-ITD-AML group (55.56%, P=0.013. The 2-year event-free survival was 29.2% in FLT3-ITD+ AML group, and it was significantly lower than that in FLT3-ITD-AML group (37.7%; P=0.04. Meanwhile, 33.3% of the patients in FLT3-ITD-AML group were also positive for NPM1 gene expression, and all of them did not get complete remission. However, only 1.39% of the patients expressed NPM1 gene in FLT3-ITD-AML group, but 50% of them got complete remission (P=0.022. Conclusion Patients with FLT3-ITD+AML were easily associated with high WBC counts, bleeding, lower CR rate, poor event-free survival, and poor prognosis.

  20. High expression of RbAp46 gene in patients with acute leukemia or chronic myelogenous leukemia in blast crisis

    Institute of Scientific and Technical Information of China (English)

    HU Shao-yan; CHEN Zi-xing; GU Wei-ying; CEN Jian-nong; ZHAO Ye

    2005-01-01

    @@ The retinoblastoma (Rb) suppressor associated protein 46 (RbAp46) also named retinoblastoma binding protein 7 (RBBP7) was first identified as a protein in HeLa cells that binds to an Rb affinity column.RbAp46 has been shown to be a core component of the mSin3 histone deacetylase (HDAC) complex1 and NuRD ( a multi-subunit complex containing chromosome-remodeling activity).2 RbAp46 is also known as the histone acetyltransferase (HAT) type B subunit 2.3 Thus,RbAp46 functions as a core-histone-binding subunit that targets chromatin assembly factors,chromatin-remodeling factors,histone acetyltransferase and deacetylase to their histone substrates in chromatin.Guan et al4 isolated RbAp46 as a downstream target gene of the Wilms'tumor suppressor gene (WT1),mediating the function of WT1.It has been discovered recently that RbAp46 specifically interacts with the BRCT domain of breast cancer and ovarian cancer susceptibility gene BRCA1 and modulates its transcriptional transactivation activity.5

  1. BCL11A expression in acute phase chronic myeloid leukemia.

    Science.gov (United States)

    Yin, Jiawei; Zhang, Fan; Tao, Huiquan; Ma, Xiao; Su, Guangsong; Xie, Xiaoli; Xu, Zhongjuan; Zheng, Yanwen; Liu, Hong; He, Chao; Mao, Zhengwei Jenny; Wang, Zhiwei; Chang, Weirong; Gale, Robert Peter; Wu, Depei; Yin, Bin

    2016-08-01

    Chronic myeloid leukemia (CML) has chronic and acute phases. In chronic phase myeloid differentiation is preserved whereas in acute phase myeloid differentiation is blocked. Acute phase CML resembles acute myeloid leukemia (AML). Chronic phase CML is caused by BCR-ABL1. What additional mutation(s) cause transition to acute phase is unknown and may differ in different persons with CML. BCL11A encodes a transcription factor and is aberrantly-expressed in several haematological and solid neoplasms. We analyzed BCL11A mRNA levels in subjects with chronic and acute phase CML. BCL11A transcript levels were increased in subjects with CML in acute phase compared with those in normals and in subjects in chronic phase including some subjects studied in both phases. BCL11A mRNA levels were correlated with percent bone marrow blasts and significantly higher in lymphoid versus myeloid blast crisis. Differentiation of K562 with butyric acid, a CML cell line, decreased BCL11A mRNA levels. Cytology and flow cytometry analyses showed that ectopic expression of BCL11A in K562 cells blocked differentiation. These data suggest BCL11A may operate in transformation of CML from chronic to acute phase in some persons. PMID:27285855

  2. Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2013-09-27

    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); Recurrent Adult Acute Myeloid Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Untreated Adult Acute Myeloid Leukemia

  3. Role of ofatumumab in treatment of chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Veliz M

    2011-05-01

    Full Text Available Marays Veliz, Javier Pinilla-IbarzH Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USAAbstract: The management of chronic lymphocytic leukemia (CLL has dramatically improved in the past decade with the addition of anti-CD20 monoclonal antibodies to the treatment armamentarium. Ofatumumab is a novel anti-CD20 monoclonal antibody recently approved in the US and Europe for the treatment of CLL refractory to alemtuzumab and fludarabine. Preclinical data showed improved complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity compared with rituximab. Clinical studies have shown single-agent activity for ofatumumab in CLL and in other low-grade non-Hodgkin's lymphomas. Combination studies are being conducted to enhance the therapeutic efficacy of ofatumumab. This paper reviews some of the key clinical studies that led to approval of ofatumumab, and future directions.Keywords: ofatumumab, chronic lymphocytic leukemia, efficacy, safety

  4. Lenalidomide in the treatment of chronic lymphocytic leukemia

    OpenAIRE

    Agostino Cortelezzi; Mariarita Sciumè; Gianluigi Reda

    2012-01-01

    The application of nucleoside analogue-based chemotherapy and immunotherapy with rituximab or alemtuzumab has increased both response rate and survival in patients with Chronic Lymphocytic Leukemia (CLL). However, because none of these therapies is curative, sequential therapeutic regimens are required. The majority of patients with relapsed or refractory CLL carry poor prognostic factors and show shorter overall survival and resistance to standard treatment. Numerous drugs have recently be...

  5. Aureobasidium pullulans infection in a patient with chronic lymphocytic leukemia

    OpenAIRE

    Leonardo Rodrigues de Oliveira; Helio Moraes-Souza; Andre Luiz Maltos; Keila Cristina dos Santos; Rodrigo Juliano Molina; Cristina Hueb Barata

    2013-01-01

    Saprophytic fungi are being increasingly recognized as etiologic agents of mycoses in immunosuppressed patients. We report a case of subcutaneous infiltration by Aureobasidium pullulans, likely due to traumatic inoculation, in a neutropenic patient during chemotherapy for chronic lymphocytic leukemia. The patient was treated with amphotericin B deoxycholate but was subsequently switched to itraconazole, which improved the lesion. This case highlights the importance of considering unusual fung...

  6. Radiation-Induced Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Ali Alkan

    2016-08-01

    Full Text Available Tumor lysis syndrome (TLS is an important oncological emergency that is usually observed with hematological malignancies and rarely with solid tumors. It can be induced either by therapy or spontaneously. Radiotherapy-induced TLS has been rarely reported in the literature. Here we present a patient with a diagnosis of metastatic prostate cancer and chronic lymphocytic leukemia complicated with TLS during palliative radiotherapy.

  7. Radiation-Induced Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Alkan, Ali; Kütük, Tuğçe; Karcı, Ebru; Yaşar, Arzu; Hiçsönmez, Ayşe; Utkan, Güngör

    2016-09-01

    Tumor lysis syndrome (TLS) is an important oncological emergency that is usually observed with hematological malignancies and rarely with solid tumors. It can be induced either by therapy or spontaneously. Radiotherapy-induced TLS has been rarely reported in the literature. Here we present a patient with a diagnosis of metastatic prostate cancer and chronic lymphocytic leukemia complicated with TLS during palliative radiotherapy. PMID:27093891

  8. Chronic Lymphocytic Leukemia: Inception to Cure: Are We There?

    OpenAIRE

    Lad, Deepesh P.; Malhotra, Pankaj; Varma, Subhash

    2012-01-01

    There have been remarkable advances in our understanding of the biology and therapeutics of chronic lymphocytic leukemia. B cell receptor signaling and micro-environment in CLL biology have been the most modern areas of research. In CLL therapeutics, we have come a long way from alkylating agents to chemo-immunotherapy. Despite this there remain significant lacunae in the disease biology that has hindered our quest to achieve the ultimate in CLL: Cure. This review aims to summarize the past, ...

  9. Antigen stimulation in the development of chronic lymphocytic leukemia.

    Science.gov (United States)

    Karp, Marta; Giannopoulos, Krzysztof

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. The mechanism the mechanism of the disease development still remains unrevealed. In recent years new unique molecular and clinical features of CLL have emerged leading to a unified hypothesis of CLL origin. Major progress in understanding CLL biology was made after identification of mutational status of immunoglobulin variable heavy chain (IGHV) genes, which also improved prediction of patients' clinical outcome. Preferential usage of IGHV genes has led to recognition of CLL-specific B cell receptors (BCRs), called stereotyped BCRs. Taken together, these data point to antigen stimulation of CLL progenitor cells. Studies on CLL antibody reactivity have shown affinity to molecular motifs on apoptotic cells and bacterial cell structures, supporting the current hypothesis of the CLL pathomechanism. In this paper we have summarized information available to date regarding current theory of cellular origin and pathology of CLL.

  10. Treatment of Chronic Myelomonocytic Leukemia with 5-Azacytidine: Case Reports

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    Peter Rohon

    2012-01-01

    Full Text Available Epigenetic therapy with hypomethylating agent (5-azacytidine; AZA is common in the management of specific subtypes of myelodysplastic syndrome (MDS, but there are only few studies in chronic myelomonocytic leukemia (CMML patients. In this paper our experience with 3 CMML patients treated with AZA is described. In one patient transfusion independency was observed after 4 treatment cycles; in one case a partial response was recorded, but a progression to acute myeloid leukemia (AML after 13 AZA cycles has appeared. In one patient, AZA in reduced dosage was administered as a bridging treatment before allogeneic stem cell transplantation (ASCT, but in the control bone marrow aspirate (before ASCT a progression to AML was recorded. Future studies are mandatory for evaluation of new molecular and clinical features which could predict the efficiency of hypomethylating agents in CMML therapy with respect to overall survival, event-free survival, quality-adjusted life year, and pharmacoeconomy.

  11. Treatment of Chronic Myelomonocytic Leukemia with 5-Azacytidine: Case Reports

    Science.gov (United States)

    Rohon, Peter; Vondrakova, Jana; Jonasova, Anna; Holzerova, Milena; Jarosova, Marie; Indrak, Karel

    2012-01-01

    Epigenetic therapy with hypomethylating agent (5-azacytidine; AZA) is common in the management of specific subtypes of myelodysplastic syndrome (MDS), but there are only few studies in chronic myelomonocytic leukemia (CMML) patients. In this paper our experience with 3 CMML patients treated with AZA is described. In one patient transfusion independency was observed after 4 treatment cycles; in one case a partial response was recorded, but a progression to acute myeloid leukemia (AML) after 13 AZA cycles has appeared. In one patient, AZA in reduced dosage was administered as a bridging treatment before allogeneic stem cell transplantation (ASCT), but in the control bone marrow aspirate (before ASCT) a progression to AML was recorded. Future studies are mandatory for evaluation of new molecular and clinical features which could predict the efficiency of hypomethylating agents in CMML therapy with respect to overall survival, event-free survival, quality-adjusted life year, and pharmacoeconomy. PMID:22937326

  12. LONG-TERM EFFECT OF HOMOHARRINGTONINE ON CHRONIC GRANULOCYTIC LEUKEMIA

    Institute of Scientific and Technical Information of China (English)

    LI Yu-feng; ZHU Jia-bin; WANG Chun-ling; DING Bang-he; LI Yuan-yuan; XUAN Heng-bao; QIAN Mo-sheng

    2005-01-01

    Objective: To observe the long-term effect of homoharringtonine (HHT) on chronic granulocytic leukemia (CGL) and its pharmacological mechanism. Methods: 76 patients with newly diagnosed early chronic phase CGL received treatment of merely 1.5 mg/m2 daily HHT for induction remission and long-term maintenance treatment. The apoptosis rate of bone marrow CD34+ cells induced by HHT was assayed with flow cytometer. Results: 86.8% patients achieved CHR, 13.2% patients PHR and 31.8% patients got cytogenetic response in HHT treatment group, which was longer than 31 (8-54) months in hydroxyurea (HU) group (P<0.05). The effect of apoptosis induction HHT was stronger on CGL-CP patients bone marrow CD34+ cells than on normal person bone marrow CD34+ cells. Conclusion: HHT is a very effective drug for remission induction and long-term maintenance treatment in early chronic phase CGL patients.

  13. Preliminary comparison of efficacy and safety of dasatinib and imatinib in newly diagnosed chronic myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    周励

    2013-01-01

    Objective To compare the efficacy and safety of dasatinib and imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia(CML-CP).Methods37CML-CP patients were randomized to receive

  14. Aureobasidium pullulans infection in a patient with chronic lymphocytic leukemia

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    Leonardo Rodrigues de Oliveira

    2013-09-01

    Full Text Available Saprophytic fungi are being increasingly recognized as etiologic agents of mycoses in immunosuppressed patients. We report a case of subcutaneous infiltration by Aureobasidium pullulans, likely due to traumatic inoculation, in a neutropenic patient during chemotherapy for chronic lymphocytic leukemia. The patient was treated with amphotericin B deoxycholate but was subsequently switched to itraconazole, which improved the lesion. This case highlights the importance of considering unusual fungal infections in critically ill patients such as those who are immunosuppressed due to chemotherapy. Diagnostic techniques and effective antifungal therapy have improved the prognosis of these cases.

  15. Myeloprolipherative disorder type chronic myeloid leukemia--eosinophilic form.

    Science.gov (United States)

    Arnautovic-Custovic, Aida; Hasic, Samira; Kopic, Emina; Jahic, Azra; Jovic, Svetlana

    2011-01-01

    Chronic eosinophilic leukemia (CEL) is a very rare form of leucemia in the western world. Adequate response is seldomly achieved after treatment with corticosteroids, interferon-alfa (INF-alfa) and medications containing hydroxi-urea (Litalir). The study presents a patient with CEL with no initial therapeutic response to the use of corticosteroids, INF-alfa and hydroxy-urea, and with neither clinical nor hematological response. After setting a diagnosis of CEL, patient was ordinated Imatinib (Glivec tabbletes) in a daily dose of 200 mg. Two days afterwards there was an evident withdrawal of subjective and clinical symptoms of disease, and the complete blood count showed significant amendment.

  16. Reverse Pseudohyperkalemia: An Important Clinical Entity in Chronic Lymphocytic Leukemia

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    Sahar Mansoor

    2015-01-01

    Full Text Available Hyperkalemia is a potentially lethal electrolyte derangement commonly seen in patients with hematologic neoplasms with or without renal failure. Pseudohyperkalemia and reverse pseudohyperkalemia also can be seen in this patient population and early recognition and diagnosis of these conditions are vital. Here, we report a case of reverse pseudohyperkalemia in a patient with chronic lymphocytic leukemia (CLL and provide recommendations regarding diagnostic and therapeutic strategies for management of such patients. Further, we discuss the pathogenesis of this condition and its potential role as a surrogate of favorable prognostic features in patients with CLL.

  17. Karyotypic findings in chronic myeloid leukemia cases undergoing treatment

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    Anupam Kaur

    2012-01-01

    Full Text Available Background: Chronic myeloid leukemia (CML is a clonal myeloproliferative expansion of primitive hematopoietic progenitor cells. Materials and Methods: In the present study, CML samples were collected from various hospitals in Amritsar, Jalandhar and Ludhiana. Results: Chromosomal alterations seen in peripheral blood lymphocytes of these treated and untreated cases of CML were satellite associations, double minutes, random loss, gain of C group chromosomes and presence of marker chromosome. No aberrations were observed in control samples. Karyotypic abnormalities have also been noted in the Ph-negative cells of some patients in disease remission. Conclusion: This is a novel phenomenon whose prognostic implications require thorough and systematic evaluation.

  18. Myeloprolipherative disorder type chronic myeloid leukemia--eosinophilic form.

    Science.gov (United States)

    Arnautovic-Custovic, Aida; Hasic, Samira; Kopic, Emina; Jahic, Azra; Jovic, Svetlana

    2011-01-01

    Chronic eosinophilic leukemia (CEL) is a very rare form of leucemia in the western world. Adequate response is seldomly achieved after treatment with corticosteroids, interferon-alfa (INF-alfa) and medications containing hydroxi-urea (Litalir). The study presents a patient with CEL with no initial therapeutic response to the use of corticosteroids, INF-alfa and hydroxy-urea, and with neither clinical nor hematological response. After setting a diagnosis of CEL, patient was ordinated Imatinib (Glivec tabbletes) in a daily dose of 200 mg. Two days afterwards there was an evident withdrawal of subjective and clinical symptoms of disease, and the complete blood count showed significant amendment. PMID:21776882

  19. Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia.

    Science.gov (United States)

    Strati, Paolo; Uhm, Joon H; Kaufmann, Timothy J; Nabhan, Chadi; Parikh, Sameer A; Hanson, Curtis A; Chaffee, Kari G; Call, Timothy G; Shanafelt, Tait D

    2016-04-01

    Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic

  20. Tyrosine kinase inhibitors induced immune thrombocytopenia in chronic myeloid leukemia?

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    Avital F. Barak

    2011-12-01

    Full Text Available The outcome and quality of life of chronic myeloid leukemia (CML patients has remarkably changed with the treatment of tyrosine kinase inhibitors (TKIs. Currently, hematopoietic stem cell transplantation (HSCT is considered mainly as a third line salvage therapy in cases of TKIs resistance or intolerance. Here we describe a patient with chronic phase CML who developed both resistance and late occurrence of s severe thrombocytopenia on first and second generation TKIs and eventually underwent HSCT. Although the mechanism of the myelosuppression is not fully understood, we showed for the first time the development of dose dependent platelet antibodies in the presence of TKIs, suggesting the possibility of TKIs induced thrombocytopenia. Our case emphasizes that late development of severe myelosuppression during imatinib treatment is probably an important indication for consideration of early HSCT.

  1. Development and targeted use of nilotinib in chronic myeloid leukemia

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    Carmen Fava

    2008-11-01

    Full Text Available Carmen Fava, Hagop Kantarjian, Jorge Cortes, Elias JabbourDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USAAbstract: The development of imatinib has resulted in sustained hematologic and cytogenetic remissions in all phases of chronic myeloid leukemia (CML. Despite the high efficacy, relapses have been observed and are much more prevalent in patients with advanced disease. The most common mechanism of acquired resistance has been traced to Bcr-Abl kinase domain mutations. Several strategies have been developed to overcome the problem of imatinib resistance, including imatinib dose escalation, novel targeted agents and combination treatments. A second generation of tyrosine kinase inhibitors was developed, which displays increased potency towards Bcr-Abl and is able to target the majority of CML mutant clones. Nilotinib (Tasigna®, AMN107, Novartis is a close analog of imatinib with approximately 20-fold higher potency for BCR-ABL kinase inhibition. Preclinical and clinical investigations demonstrate that nilotinib effectively overcomes imatinib resistance, and has induced high rates of hematologic and cytogenetic responses in CML post imatinib failure, with a good tolerance. Nilotinib has been approved for CML patients in chronic and accelerated phases, post imatinib failure.Keywords: nilotinib, imatinib-resistance, imatinib-intolerance, CML

  2. Targeted treatment for chronic lymphocytic leukemia: clinical potential of obinutuzumab

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    Smolej L

    2014-12-01

    Full Text Available Lukáš Smolej 4th Department of Internal Medicine – Hematology, University Hospital Hradec Králové and Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic Abstract: Introduction of targeted agents revolutionized the treatment of chronic lymphocytic leukemia (CLL in the past decade. Addition of chimeric monoclonal anti-CD20 antibody rituximab to chemotherapy significantly improved efficacy including overall survival (OS in untreated fit patients; humanized anti-CD52 antibody alemtuzumab and fully human anti-CD20 antibody ofatumumab lead to improvement in refractory disease. Novel small molecule inhibitors such as ibrutinib and idelalisib demonstrated excellent activity and were very recently licensed in relapsed/refractory CLL. Obinutuzumab (GA101 is the newest monoclonal antibody approved for the treatment of CLL. This novel, glycoengineered, type II humanized anti-CD20 antibody is characterized by enhanced antibody-dependent cellular cytotoxicity and direct induction of cell death compared to type I antibodies. Combination of obinutuzumab and chlorambucil yielded significantly better OS in comparison to chlorambucil monotherapy in untreated comorbid patients. These results led to approval of obinuzutumab for the treatment of CLL. Numerous clinical trials combining obinutuzumab with other cytotoxic drugs and novel small molecules are currently under way. This review focuses on the role of obinutuzumab in the treatment of CLL. Keywords: chronic lymphocytic leukemia, anti-CD20 antibodies, chlorambucil, rituximab, ofatumumab, obinutuzumab, overall survival

  3. Rituximab for the treatment of patients with chronic lymphocytic leukemia

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    M Gentile

    2010-03-01

    Full Text Available M Gentile, E Vigna, C Mazzone, E Lucia, AG Recchia, L Morabito2, MG Bisconte, C Gentile, F Morabito1UOC di Ematologia, Azienda Ospedaliera di Cosenza, Italy; 2Servicio de Hematología y Hemoterapia, Hospital Universitario de Canarias, La Laguna, Tenerife, SpainAbstract: Chronic lymphocytic leukemia (CLL is a lymphoproliferative disorder that originates from antigen-experienced B lymphocytes that do not die and hence accumulate due to external survival signals or undergo apoptosis and are replenished by proliferating precursors. These neoplastic lymphocytes exhibit a characteristic immunophenotype of CD5+/CD19+/CD20+/HLA-DR+/CD23+/sIgdim. Thus, the CD20 antigen has been an appealing target for therapy. The introduction of the monoclonal antibody rituximab (anti-CD20 enabled an outstanding advance in CLL treatment. The introduction of this monoclonal antibody into chemotherapy regimens has dramatically improved complete response rates and progression-free survival in patients with both untreated and relapsed CLL. Although only preliminary data from phase III confirmatory trials have been reported, the FCR regimen, which combines fludarabine and cyclophosphamide with rituximab, is currently the most effective treatment regimen for CLL patients, and has also been demonstrated to significantly improve overall survival . The success of rituximab and the identification of other CLL lymphocyte surface antigens have spurred the development of a multitude of monoclonal antibodies targeting distinct proteins and epitopes in an attempt to target CLL cells more effectively.Keywords: rituximab, chronic lymphocytic leukemia, chemotherapy

  4. Perforation of the Colon During Imatinib Mesylate (Gleevec) Treatment in a Patient with Chronic Myeloid Leukemia (CML).

    Science.gov (United States)

    El Jurdi, Najla; Bankoff, Mark; Klein, Andreas; Saif, Muhammad W

    2016-01-01

    Imatinib (Gleevec; STI-571) is a tyrosine-kinase inhibitor (TKI) used in the treatment of multiple cancers, most notably Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) as well as gastrointestinal stromal tumor (GIST). The most common adverse effects with imatinib include superficial edema, muscle cramps, musculoskeletal pain, rash, fatigue, headache, and gastrointestinal side effects. Less frequent side effects include pancytopenia, febrile neutropenia, flushing, and liver function test abnormalities. Very rare side effects include secondary malignancies, Sweet's syndrome, angioedema, or cardiac arrest. We report the first case report of gastrointestinal perforation complicating imatinib treatment for CML. Unlike other antiangiogenic TKIs such as sunitinib or sorafenib that target vascular endothelial growth factor (VEGF) and known to cause gastrointestinal perforation, imatininib is a TKI with no known anti-VEGF activity, and so it remains unclear how imatinib would be associated with developing this life threatening complication. However, physicians caring for patients of imatinib should be aware of this potential toxicity. We suggest that careful attention and an appropriate clinical evaluation are required for patients presenting with gastrointestinal symptoms during imatinib treatment. PMID:27489753

  5. T-Cell Depleted Allogeneic Stem Cell Transplantation for Patients With Hematologic Malignancies

    Science.gov (United States)

    2015-10-05

    Acute Myelogenous Leukemia; Lymphoid Leukemia; Chronic Myelogenous Leukemia; Malignant Lymphoma; Hodgkin's Disease; Chronic Lymphocytic Leukemia; Myeloproliferative Disorder; Anemia, Aplastic; Myelodysplastic Syndromes

  6. Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2016-09-23

    Anemia; Fever, Sweat, and Hot Flashes; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma; Weight Change

  7. Juvenile Myelomonocytic Leukemia

    Science.gov (United States)

    ... myeloproliferative neoplasms, leukemia , and other conditions . Chronic Myelomonocytic Leukemia Key Points Chronic myelomonocytic leukemia is a disease ... chance of recovery) and treatment options. Chronic myelomonocytic leukemia is a disease in which too many myelocytes ...

  8. Spontaneous chronic subdural hematoma development in chronic myeloid leukemia cases at remission phase under maintenance therapy, management strategy - a series with literature review

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    Raheja Amol

    2016-09-01

    Full Text Available Chronic subdural hematoma (CSDH is common squeal of trauma and rarely associated with anticoagulant therapy, antiplatelet, chemotherapeutic drugs, arteriovenous malformation, aneurysms and post-craniotomy. However its occurrence is very unusual with systemic haematological malignancy and mostly reported with acute myeloid leukemia; however incidence of SDH occurrence in chronic myelogenous leukemia (CML is very rare. CML is a haematological malignancy characterized by chromosomal alteration, pathologically represents increased proliferation of the granulocytic cell line without loss of capacity to differentiate. CML has three phases - remission phase, accelerated phase and blast crisis. About 85 % of patients present in remission phase of disease and carries a favorable prognosis. As intracranial, subdural hematoma usually occur in the accelerated phase or blast crisis phase or extremely uncommon during chronic remission phase, although only those affected, who are neglecting therapeutic medication or discontinued therapy or rarely as an adverse effect of medications. However, important role of neurosurgeon lies in early detection and correction of platelet count and associated hematological abnormality as quite sizeable proportion of cases may not need surgical intervention instead can be managed conservatively under regular supervision in association with oncologist colleague, but few cases may need urgent surgical intervention. So, selecting a subgroup of CML cases in the remission phase requiring surgical intervention, presenting with CSDH is not only challenging, as failure to make an informed and timely precise decision can lead to catastrophic worse outcome and even mortality. So, purpose of current article is to formulate the management therapeutic plan. Authors report three cases of CML in chronic remission phase, receiving treatment under guidance of Haemto-oncologist at our institute presented with spontaneous chronic SDH. The mean

  9. Chronic Myeloid Leukemia (CML) Mouse Model in Translational Research.

    Science.gov (United States)

    Peng, Cong; Li, Shaoguang

    2016-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by increased proliferation of granulocytic cells without the loss of their capability to differentiate. CML is a clonal disease, originated at the level of Hematopoietic Stem Cells with the Philadelphia chromosome resulting from a reciprocal translocation between the chromosomes 9 and 22t(9;22)-(q34;q11). This translocation produces a fusion gene known as BCR-ABL which acquires uncontrolled tyrosine kinase activity, constantly turning on its downstream signaling molecules/pathways, and promoting proliferation of leukemia cell through anti-apoptosis and acquisition of additional mutations. To evaluate the role of each critical downstream signaling molecule of BCR-ABL and test therapeutic drugs in vivo, it is important to use physiological mouse disease models. Here, we describe a mouse model of CML induced by BCR-ABL retrovirus (MSCV-BCR-ABL-GFP; MIG-BCR-ABL) and how to use this model in translational research.Moreover, to expand the application of this retrovirus induced CML model in a lot of conditional knockout mouse strain, we modified this vector to a triple gene coexpression vector in which we can co-express BCR-ABL, GFP, and a third gene which will be tested in different systems. To apply this triple gene system in conditional gene knockout strains, we can validate the CML development in the knockout mice and trace the leukemia cell following the GFP marker. In this protocol, we also describe how we utilize this triple gene system to prove the function of Pten as a tumor suppressor in leukemogenesis. Overall, this triple gene system expands our research spectrum in current conditional gene knockout strains and benefits our CML translational research. PMID:27150093

  10. Trisomy 12 in chronic lymphocytic leukemia and hairy cell leukemia: a cytogenetic and interphase cytogenetic study.

    Science.gov (United States)

    Cuneo, A; Bigoni, R; Balboni, M; Carli, M G; Piva, N; Fagioli, F; Latorraca, A; Wlodarska, I; van den Berghe, H; Castoldi, G

    1994-09-01

    Fluorescent in situ hybridization (FISH) with a chromosome 12-specific pericentromeric probe was performed in 42 patients with B-cell chronic lymphocytic leukemia (CLL) and in 10 patients with hairy cell leukemia (HCL). In all cases, a normal karyotype in more than 10 metaphase cells was obtained by conventional chromosome study. FISH documented that 6/42 patients with CLL in fact had trisomy 12 in 15-49% interphase cells. Sequential FISH studies were performed in 2 cases, showing an increase of percentage of trisomic cells over a 2-month to 4-year period. Two out of 10 patients with HCL, one of whom had morphologic features consistent with a diagnosis of HCL variant, showed 5.5 and 10% interphase nuclei with three fluorescent signals, a finding suggestive of the presence of trisomy 12. Combined immunophenotyping and FISH staining in these patients with HCL documented that trisomic cells were CD11c-positive, CD13-negative, and CD2-negative. We conclude that FISH is a sensitive technique allowing for the detection of trisomy 12 in a fraction of cytogenetically normal patients affected with CLL and HCL. PMID:7858495

  11. Decreased deformability of lymphocytes in chronic lymphocytic leukemia

    Science.gov (United States)

    Zheng, Yi; Wen, Jun; Nguyen, John; Cachia, Mark A.; Wang, Chen; Sun, Yu

    2015-01-01

    This paper reports the first study of stiffness/deformability changes of lymphocytes in chronic lymphocytic leukemia (CLL) patients, demonstrating that at the single cell level, leukemic metastasis progresses are accompanied by biophysical property alterations. A microfluidic device was utilized to electrically measure cell volume and transit time of single lymphocytes from healthy and CLL patients. The results from testing thousands of cells reveal that lymphocytes from CLL patients have higher stiffness (i.e., lower deformability), as compared to lymphocytes in healthy samples, which was also confirmed by AFM indentation tests. This observation is in sharp contrast to the known knowledge on other types of metastatic cells (e.g., breast and lung cancer cells) whose stiffness becomes lower as metastasis progresses.

  12. Gene Expression Pattern of Signal Transduction in Chronic Myeloid Leukemia

    Institute of Scientific and Technical Information of China (English)

    LI Huiyu; JIE Shenghua; GUO Tiannan; HUANG Shi'ang

    2006-01-01

    To explore the transcriptional gene expression profiles of signaling pathway in Chronic myeloid leukemia (CML), a series of cDNA microarray chips were tested. The results showed that differentially expressed genes related to singal transduction in CML were screened out and the genes involved in Phosphoinositide 3-kinases (PI3K), Ras-MAPK (mitogen-activated protein kinase) and other signaling pathway genes simultaneously. The results also showed that most of these genes were up-expression genes , which suggested that signal transduction be overactivated in CML. Further analysis of these differentially expressed signal transduction genes will be helpful to understand the molecular mechanism of CML and find new targets of treatment.

  13. REGULATORY T-CELLS IN CHRONIC LYMPHOCYTIC LEUKEMIA

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    Giovanni D'arena

    2012-08-01

    Full Text Available Regulatory T-cells (Tregs constitute a small subset of cells that are actively involved in maintaining self-tolerance, in immune homeostasis and in antitumor immunity. They are thought to play a significant role in the progression of cancer and are generally increased in patient with chronic lymphocytic leukemia (CLL. Their number correlates with more aggressive disease status and is predictive of the time to treatment, as well. Moreover, it is now clear that dysregulation in Tregs cell frequency and/or function may result in a plethora of autoimmune diseases, including multiple sclerosis, type 1 diabetes mellitus, myasthenia gravis, systemic lupus erythematosis, autoimmune lymphoproliferative disorders, rheumatoid arthritis, and psoriasis. Efforts are made aiming to develop approaches to deplete Tregs or inhibit their function in either cancer and autoimmune disorders.

  14. Docosahexaenoic acid induces apoptosis in primary chronic lymphocytic leukemia cells

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    Romain Guièze

    2015-12-01

    Full Text Available Chronic lymphocytic leukemia is an indolent disorder with an increased infectious risk remaining one of the main causes of death. Development of therapies with higher safety profile is thus a challenging issue. Docosahexaenoic acid (DHA, 22:6 is an omega-3 fatty acid, a natural compound of normal cells, and has been shown to display antitumor potency in cancer. We evaluated the potential in vitro effect of DHA in primary CLL cells. DHA induces high level of in vitro apoptosis compared to oleic acid in a dose-dependent and time-dependent manner. Estimation of IC50 was only of 4.813 μM, which appears lower than those reported in solid cancers. DHA is highly active on CLL cells in vitro. This observation provides a rationale for further studies aiming to understand its mechanisms of action and its potent in vivo activity.

  15. Molecular Detection of BCR-ABL in Chronic Myeloid Leukemia.

    Science.gov (United States)

    Qin, Ya-Zhen; Huang, Xiao-Jun

    2016-01-01

    All chronic myeloid leukemia (CML) patients have the BCR-ABL fusion gene. The constitutively activated BCR-ABL tyrosine kinase is a critical pathogenetic event in CML. Tyrosine kinase inhibitors (TKIs), such as imatinib, are synthesized small molecules that primarily target BCR-ABL tyrosine kinases and have become a first-line treatment for CML. Detection of BCR-ABL transcript level by real-time quantitative polymerase chain reaction (RQ-PCR) is a clinical routine for evaluating TKI treatment efficacy and predicting long-term response. Furthermore, because they are a main TKI resistance mechanism, the BCR-ABL tyrosine kinase domain (TKD) point mutations that are detected by Sanger sequencing can help clinicians make decisions on subsequent treatment selections. Here, we present protocols for the two abovementioned molecular methods for CML analysis. PMID:27581134

  16. Osthole shows the potential to overcome P-glycoprotein‑mediated multidrug resistance in human myelogenous leukemia K562/ADM cells by inhibiting the PI3K/Akt signaling pathway.

    Science.gov (United States)

    Wang, Hong; Jia, Xiu-Hong; Chen, Jie-Ru; Wang, Jian-Yong; Li, You-Jie

    2016-06-01

    P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) has been reported to play a pivotal role in tumor chemotherapy failure. Study after study has illustrated that the phosphoinositide 3-kinase (PI3K)/Akt signaling cascade is involved in the MDR phenotype and is correlated with P-gp expression in many human malignancies. In the present study, osthole, an O-methylated coumarin, exhibited potent reversal capability of MDR in myelogenous leukemia K562/ADM cells. Simultaneously, the uptake and efflux of Rhodamine-123 (Rh-123) and the accumulation of doxorubicin assays combined with flow cytometric analysis suggested that osthole could increase intracellular drug accumulation. Furthermore, osthole decreased the expression of multidrug resistance gene 1 (MDR1) at both the mRNA and protein levels. Further experiments elucidated that osthole could suppress P-gp expression by inhibiting the PI3K/Akt signaling pathway which might be the main mechanism accounting for the reversal potential of osthole in the MDR in K562/ADM cells. In conclusion, osthole combats MDR and could be a promising candidate for the development of novel MDR reversal modulators. PMID:27109742

  17. BME, a novel compound of anthraquinone, down regulated P-glycoprotein expression in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells via generation of reactive oxygen species.

    Science.gov (United States)

    Wang, Jianhong; Liu, Lu; Cen, Juan; Ji, Biansheng

    2015-09-01

    P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in tumor cells is still a main obstacle for the chemotherapeutic treatment of cancers. Thus, development of effective MDR reversing agents is an important approach in the clinic. The present study revealed that BME, a novel compound of anthraquinone, elevated intracellular accumulation of the P-gp substrates and reduced concentration resulting in 50% inhibition of cell growth (IC50) values for doxorubicin (DOX) in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells. Further more, BME was also reported to down regulated P-gp expression accompanying with generation of nontoxic low level of intracellular reactive oxygen species (iROS) and activation of extracellular signal-regulated kinase (ERK)1/2 as well as c-JUN N-terminal kinase (JNK). However, treatment with N-acetyl-cysteine (NAC), U0216 and SP600125 almost abolished actions of the BME mentioned above. These results indicated that the effect of the BME on the P-gp may be involved in generation of nontoxic low level of iROS and activation of ERK1/2 or JNK, which suggested valuable clues to screen and develop P-gp reversing agents.

  18. The expression of PML in chronic myeloid leukemia and effect on cell proliferation

    Institute of Scientific and Technical Information of China (English)

    吴洁

    2013-01-01

    Objective To investigate whether PML is expressed differently in chronic myeloid leukemia (CML) patients and healthy controls,then explore the effect of PML on proliferation in leukemia cell lines K562.Methods Realtime PCR was used to detect the PML expression in

  19. Treatments for chronic myeloid leukemia: a qualitative systematic review

    Directory of Open Access Journals (Sweden)

    Ferdin

    2012-08-01

    Full Text Available Roxanne Ferdinand,1 Stephen A Mitchell,2 Sarah Batson,2 Indra Tumur11Pfizer, Tadworth, UK; 2Abacus International, Bicester, UKBackground: Chronic myeloid leukemia (CML is a myeloproliferative disorder of blood stem cells. The tyrosine kinase inhibitor (TKI imatinib was the first targeted therapy licensed for patients with chronic-phase CML, and its introduction was associated with substantial improvements in response and survival compared with previous therapies. Clinical trial data are now available for the second-generation TKIs (nilotinib, dasatinib, and bosutinib in the first-, second-, and third-line settings. A qualitative systematic review was conducted to qualitatively compare the clinical effectiveness, safety, and effect on quality of life of TKIs for the management of chronic-, accelerated-, or blast-phase CML patients.Methods: Included studies were identified through a search of electronic databases in September 2011, relevant conference proceedings and the grey literature.Results: In the first-line setting, the long-term efficacy (up to 8 years of imatinib has been confirmed in a single randomized controlled trial (International Randomized Study of Interferon [IRIS]. All second-generation TKIs reported lower rates of transformation, and comparable or superior complete cytogenetic response (CCyR, major molecular response (MMR, and complete molecular response rates compared with imatinib by 2-year follow-up. Each of the second-generation TKIs was associated with a distinct adverse-event profile. Bosutinib was the only second-generation TKI to report quality-of-life data (no significant difference compared with imatinib treatment. Data in the second- and third-line setting confirmed the efficacy of the second-generation TKIs in either imatinib-resistant or -intolerant patients, as measured by CCyR and MMR rates.Conclusion: Data from first-line randomized controlled trials reporting up to 2-year follow-up indicate superior response

  20. PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Weisser, Martin; Yeh, Ru-Fang; Duchateau-Nguyen, Guillemette;

    2014-01-01

    Addition of rituximab (R) to fludarabine and cyclophosphamide (FC) has significantly improved patient outcomes in chronic lymphocytic leukemia (CLL). Whether baseline gene expression can identify patients who will benefit from immunochemotherapy over chemotherapy alone has not been determined. We...

  1. Allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia:a report of 12 patients

    Institute of Scientific and Technical Information of China (English)

    孙于谦

    2013-01-01

    Objective To retrospectively review the efficacy of allogeneic hematopoietic stem cell transplantation(allo-HSCT)for chronic myelomonocytic leukemia(CMML).Methods The engraftment,graft versus host disease(GVHD)

  2. Ibrutinib Improves Survival in Patients with Previously Treated Chronic Lymphocytic Leukemia

    Science.gov (United States)

    A summary of results from an international phase III trial that compared ibrutinib (Imbruvica®) and ofatumumab (Arzerra®) for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

  3. Safety and Tolerability Study of PCI-32765 in B Cell Lymphoma and Chronic Lymphocytic Leukemia

    Science.gov (United States)

    2016-04-26

    B-cell Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Well-differentiated Lymphocytic Lymphoma; B Cell Lymphoma; Follicular Lymphoma,; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Waldenstrom Macroglobulinemia; Burkitt Lymphoma; B-Cell Diffuse Lymphoma

  4. Diagnosis of chronic myeloid leukemia from acute intracerebral hemorrhage:a case report

    Institute of Scientific and Technical Information of China (English)

    Chakroun-Walha Olfa; Rejeb Imen; Kammoun Leila; Ksibi Hichem; Ayadi Adnane; Chaari Mourad; Chaari Adel; Kallel Choumous; Rekik Noureddine

    2015-01-01

    Intracerebral hemorrhage (ICH) is frequent pathology in emergency departments. Coagulopathies leading to ICH are rare. We describe here the case of diagnosis of a chronic myeloid leukemia from ICH in emergencies.

  5. Presence of alternative lengthening of telomeres associated circular extrachromosome telomere repeats in primary leukemia cells of chronic myeloid leukemia

    OpenAIRE

    Samassekou, Oumar; Malina, Abba; Hébert, Josée; Yan, Ju

    2013-01-01

    Background The predominant mechanism by which human tumors maintain telomere length is via telomerase. In ~10% of tumor samples, however, telomere length is conserved, despite no detectable telomerase activity, in part through activation of the alternative lengthening of telomeres (ALT) pathway. Methods We studied the circular extra-chromosomal telomeric repeat (ECTR), an ALT hallmark, and telomerase activity in 24 chronic myeloid leukemia (CML) patients in chronic phase (CP). Results We iden...

  6. Knockdown of HOXA10 reverses the multidrug resistance of human chronic mylogenous leukemia K562/ADM cells by downregulating P-gp and MRP-1.

    Science.gov (United States)

    Yi, Ying-Jie; Jia, Xiu-Hong; Wang, Jian-Yong; Li, You-Jie; Wang, Hong; Xie, Shu-Yang

    2016-05-01

    Multidrug resistance (MDR) of leukemia cells is a major obstacle in chemotherapeutic treatment. The high expression and constitutive activation of P-glycoprotein (P-gp) and multidrug resistance protein-1 (MRP-1) have been reported to play a vital role in enhancing cell resistance to anticancer drugs in many tumors. The present study aimed to investigate the reversal of MDR by silencing homeobox A10 (HOXA10) in adriamycin (ADR)-resistant human chronic myelogenous leukemia (CML) K562/ADM cells by modulating the expression of P-gp and MRP-1. K562/ADM cells were stably transfected with HOXA10-targeted short hairpin RNA (shRNA). The results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis showed that the mRNA and protein expression of HOXA10 was markedly suppressed following transfection with a shRNA-containing vector. The sensitivity of the K562/ADM cells to ADR was enhanced by the silencing of HOXA10, due to the increased intracellular accumulation of ADR. The accumulation of ADR induced by the silencing of HOXA10 may be due to the downregulation of P-gp and MRP-1. Western blot analysis revealed that downregulating HOXA10 inhibited the protein expression of P-gp and MRP-1. Taken together, these results suggest that knockdown of HOXA10 combats resistance and that HOXA10 is a potential target for resistant human CML. PMID:27035504

  7. Paranasal Manifestations of Early Stage Chronic Lymphocytic Leukemia

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    Ceren Günel

    2015-04-01

    Full Text Available OBJECTIVE: Chronic lymphocytic leukemia (CLL is the most common adult leukemia. A few studies have been reported about the relationship between CLL and paranasal sinuses. We aimed to investigate the paranasal manifestations of CLL and to determine the expression of nuclear factor-ĸB (NF-kB and tumor necrosis factor (TNF-α in the nasal mucosa in patients with CLL. MATERIALS AND METHODS: This study was a clinical trial that involved 40 patients. Group CLL (n=20 consisted of patients with early-stage CLL who were followed-up at the hematology clinic and who did not receive any treatment. The control group (n=20 consisted of patients who had undergone concha surgery because of nasal obstruction. Paranasal sinus computer tomography scans of all patients were taken, they were scored on the basis of the Lund–Mackay system, and sinusitis findings were recorded. The biopsy material taken from the inferior concha head of all patients was immunohistochemically stained with primary antibodies against NF-kB and TNF-α. RESULTS: There were no statistically significant differences between the two groups with respect to NF-κB (p=0.716 and TNF-α staining scores (p=1.000. The Lund–Mackay scores were significantly higher in the CLL group than in the control group (p=0.004. Fourteen patients had sinusitis at different locations, while the most common diagnosis was maxillary sinusitis (n=8 in the CLL group. CONCLUSION: This study showed that patients with early-stage CLL tend to have rhinosinusitis. However, NF-kB and TNF-α may not have a role in the inflammatory process involving the paranasal sinuses in patients with CLL.

  8. Chronic subdural hematoma in a child with acute myeloid leukemia after leukocytosis

    Directory of Open Access Journals (Sweden)

    Mehmet Basmaci

    2012-01-01

    Full Text Available Severe complications that develop in the early stages in patients with acute leukemia have a mortal course. Bleeding, leukostasis, and less frequently, infections are responsible for early mortality. Hemorrhage is most common in acute leukemia and usually leads to death. Hemorrhage may occur due to chemotherapy or bone marrow transplantation in patients with acute leukemia. Leukocytosis, thrombocytopenia, sepsis, and coagulopathy increase the risk of bleeding. There may be multiple etiologic factors. Subdural or subarachnoid hemorrhage is less common than an intra-axial hemorrhage. The incidence of spontaneous subdural hematoma is higher in patients with leukemia. Although advances in the treatment of platelet transfusion and disseminated intravascular coagulation have decreased the incidence of hemorrhagic complications in patients receiving chemotherapy for acute leukemia, intracranial hemorrhage-related deaths are a significant problem. We discussed the etiology and management of chronic subdural hematoma detected in a two-year-old male patient with Acute Myeloid Leukemia and hyperleukocytosis.

  9. Transformation from atypical chronic myeloid leukemia to chronic myelomonocytic leukemia as progression of myeloid neoplasm with platelet-derived growth factor ß rearrangement

    Directory of Open Access Journals (Sweden)

    Xue Shi

    2015-01-01

    Full Text Available Myeloid neoplasms associated with platelet-derived growth factor b (PDGFRB rearrangement usually keep only one morphologic type unless blast crisis. We describe a unique case of hematological features transformation from atypical chronic myeloid leukemia to chronic myelomonocytic leukemia, and imatinib showed no clinical therapeutic effects. The phenomenon indicates that different types of myeloid neoplasms associated with PDGFRB rearrangement can transform into one another with the progression of the disease, and to some extent, this transformation suggests the aggravation of disease.

  10. Identification of homogeneously staining regions in leukemia patients

    Directory of Open Access Journals (Sweden)

    Mohammad Heydarian Moghadam

    2013-01-01

    Full Text Available Homogeneously staining regions (HSR or double minute chromosomes (dmin are autonomously replicating extra-chromosomal elements that are frequently associated with gene amplification in a variety of cancers. The diagnosis of leukemia patients was based on characterization of the leukemic cells obtained from bone marrow cytogenetics. This study report two cases, one with Acute Myeloblastic Leukemia without maturation (AML-M1, aged 23-year-old female, and the other with chronic myelogenous leukemia (CML-blast crisis, a 28-year-old female associated with double minute chromosomes. Most cases of acute myeloid leukemia with dmin in the literature (including our cases have been diagnosed as having acute myeloid leukemia.

  11. Understanding and Targeting the Wnt/β-Catenin Signaling Pathway in Chronic Leukemia

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    S. Thanendrarajan

    2011-01-01

    Full Text Available It has been revealed that the Wnt/β-catenin signaling pathway plays an important role in the development of solid tumors and hematological malignancies, particularly in B-cell neoplasia and leukemia. In the last decade there have been made experimental approaches targeting the Wnt pathway in chronic leukemia. In this paper we provide an overview about the current state of knowledge regarding the Wnt/β-catenin signaling pathway in chronic leukemia with special focus on therapeutic options and strategies.

  12. Deletions of Immunoglobulin heavy chain and T cell receptor gene regions are uniquely associated with lymphoid blast transformation of chronic myeloid leukemia

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    Valgañon Mikel

    2010-01-01

    Full Text Available Abstract Background Chronic myelogenous leukemia (CML results from the neoplastic transformation of a haematopoietic stem cell. The hallmark genetic abnormality of CML is a chimeric BCR/ABL1 fusion gene resulting from the Philadelphia chromosome rearrangement t(9;22(q34;q11. Clinical and laboratory studies indicate that the BCR/ABL1 fusion protein is essential for initiation, maintenance and progression of CML, yet the event(s driving the transformation from chronic phase to blast phase are poorly understood. Results Here we report multiple genome aberrations in a collection of 78 CML and 14 control samples by oligonucleotide array comparative genomic hybridization. We found a unique signature of genome deletions within the immunoglobulin heavy chain (IGH and T cell receptor regions (TCR, frequently accompanied by concomitant loss of sequences within the short arm regions of chromosomes 7 and 9, including IKZF1, HOXA7, CDKN2A/2B, MLLT3, IFNA/B, RNF38, PAX5, JMJD2C and PDCD1LG2 genes. Conclusions None of these genome losses were detected in any of the CML samples with myeloid transformation, chronic phase or controls, indicating that their presence is obligatory for the development of a malignant clone with a lymphoid phenotype. Notably, the coincidental deletions at IGH and TCR regions appear to precede the loss of IKZF1 and/or p16 genes in CML indicating a possible involvement of RAG in these deletions.

  13. Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rγc-deficient mice

    OpenAIRE

    Sarry, Jean-Emmanuel; Murphy, Kathleen; Perry, Robin; Sanchez, Patricia V.; Secreto, Anthony; Keefer, Cathy; Swider, Cezary R.; Strzelecki, Anne-Claire; Cavelier, Cindy; Récher, Christian; Mansat-De Mas, Véronique; Delabesse, Eric; Danet-Desnoyers, G; Carroll, Martin

    2010-01-01

    Human leukemic stem cells, like other cancer stem cells, are hypothesized to be rare, capable of incomplete differentiation, and restricted to a phenotype associated with early hematopoietic progenitors or stem cells. However, recent work in other types of tumors has challenged the cancer stem cell model. Using a robust model of xenotransplantation based on NOD/SCID/IL2Rγc-deficient mice, we confirmed that human leukemic stem cells, functionally defined by us as SCID leukemia-initiating cells...

  14. Acute Leukemia: Diagnosis, Management, and Potential for Cure

    OpenAIRE

    Stewart, Keith; Keating, Armand

    1988-01-01

    Acute leukemia is an uncommon malignant disorder resulting from the clonal proliferation of hematopoietic precursors of the myeloid or lymphoid lineages. Of the two major subgroups, acute lymphoblastic leukemia is more common in children, while acute myelogenous leukemia predominates in adults. With modern chemotherapy 60%-70% of all children with acute lymphoblastic leukemia can be long-term survivors and are potentially cured. Although the prognosis in acute myelogenous leukemia is less fav...

  15. Lenalidomide in the Treatment of Chronic Lymphocytic Leukemia

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    Agostino Cortelezzi

    2012-01-01

    Full Text Available The application of nucleoside analogue-based chemotherapy and immunotherapy with rituximab or alemtuzumab has increased both response rate and survival in patients with Chronic Lymphocytic Leukemia (CLL. However, because none of these therapies is curative, sequential therapeutic regimens are required. The majority of patients with relapsed or refractory CLL carry poor prognostic factors and show shorter overall survival and resistance to standard treatment. Numerous drugs have recently been approved for CLL therapy and many novel agents are under clinical investigation. The role of the tumor microenvironment and of immune dysfunction in CLL have allowed to enlarge the therapeutic armamentarium for CLL patients. This article will provide a comprehensive summary regarding mechanism of action, efficacy and safety of lenalidomide in CLL patients. Relevant clinical trials using lenalidomide alone or in combinations are discussed. Lenalidomide shows good activity also in relapsed/refractory or treatment-naive CLL patients. Definitive data from ongoing studies are needed to validate overall and progression-free survival. The toxicity profile might limit lenalidomide use because it can result in serious side effects, but largely controlled by gradual dose escalation. Further understanding of the exact mechanism of action in CLL will allow more efficacious use of lenalidomide alone or in combination regimens.

  16. A case of chronic lymphocytic leukemia with massive ascites

    Directory of Open Access Journals (Sweden)

    Meliha Nalcaci

    2012-10-01

    Full Text Available An 81-year old woman with a history of chronic lymphocytic leukemia (CLL was admitted with night sweats and abdominal distension. A complete blood count showed hemoglobin 5 g/dL, white blood cell (WBC count 28.5x109/L and platelets 38.4x109/L. Peripheral blood smear examination showed a large number of smudge cells and lymphocytosis composed of mature-looking lymphocytes with clumped nuclear chromatin. Computed tomography scan demonstrated enlarged cervical, axillary, paraaortic, retroperitoneal and mesenteric lymph nodes with concomitant omental thickening and ascites. Also, the liver and the spleen were enlarged in the presence of multiple ill-defined hypoechoic areas in the latter. Histopathological analysis of the cervical lymph node biopsy was consistent with CLL. Bone marrow examination showed diffuse infiltration of the marrow with small lymphocytes. Analysis of the ascitic fluid revealed an exudate with WBC 1220 cells/mL. Cytocentrifuge preparation of the ascitic fluid showed small mature lymphoid cells containing hyperchromatic nuclei with coarsely gran- ular chromatin. On flow cytometric analysis of the ascitic fluid, expression of CD5, CD19, CD20, CD22, CD23, CD45 and HLA-DR was compatible with a diagnosis of CLL, in accordance with the results of the peripheral blood analysis. The patient was treated with chemotherapy consisting of cyclophosphamide, vincristine and prednisolone but died within one month after development of non-chylous ascites.

  17. Red cell ferritin and iron stores in chronic granulocytic leukemia

    International Nuclear Information System (INIS)

    Basic red cell ferritin was investigated in 28 patients with different phases of chronic granulocytic leukemia (GCL). Red cell ferritin was significantly decreased in remission after busulphan treatment and significantly elevated in the blast crisis as compared to healthy controls. Bone marrow stainable iron was decreased or absent in 86% of patients in the initial phase at the time of diagnosis and in 92% of those in remission. Red cell ferritin correlated with serum ferritin, however, serum ferritin level remained above normal range during all phases of the disease. A negative correlation between red cell ferritin and hemoglobin (Hb) (r = -0.605, p < 0.001) suggested that red cell ferritin level reflected the rate of iron utilization for heme synthesis. Decrease red cell iron observed in the remission may be explained by regression of dyserythropoiesis and by restoration of normal Hb synthesis after busulphan treatment. A progressive dyserythropoiesis in the blast crisis may lead to an increased red cell ferritin level. (author)

  18. A case of chronic lymphocytic leukemia with massive ascites

    Science.gov (United States)

    Yonal, Ipek; Nazlıgul, Esra; Tas, Gulsum; Agan, Mehmet Ramazan; Yenerel, Mustafa Nuri; Nalcaci, Meliha

    2012-01-01

    An 81-year old woman with a history of chronic lymphocytic leukemia (CLL) was admitted with night sweats and abdominal distension. A complete blood count showed hemoglobin 5 g/dL, white blood cell (WBC) count 28.5×109/L and platelets 38.4×109/L. Peripheral blood smear examination showed a large number of smudge cells and lymphocytosis composed of mature-looking lymphocytes with clumped nuclear chromatin. Computed tomography scan demonstrated enlarged cervical, axillary, paraaortic, retroperitoneal and mesenteric lymph nodes with concomitant omental thickening and ascites. Also, the liver and the spleen were enlarged in the presence of multiple ill-defined hypoechoic areas in the latter. Histopathological analysis of the cervical lymph node biopsy was consistent with CLL. Bone marrow examination showed diffuse infiltration of the marrow with small lymphocytes. Analysis of the ascitic fluid revealed an exudate with WBC 1220 cells/mL. Cytocentrifuge preparation of the ascitic fluid showed small mature lymphoid cells containing hyperchromatic nuclei with coarsely granular chromatin. On flow cytometric analysis of the ascitic fluid, expression of CD5, CD19, CD20, CD22, CD23, CD45 and HLA-DR was compatible with a diagnosis of CLL, in accordance with the results of the peripheral blood analysis. The patient was treated with chemotherapy consisting of cyclophosphamide, vincristine and prednisolone but died within one month after development of non-chylous ascites. PMID:23372915

  19. Defective regulation of leukemic hematopoiesis in chronic myeloid leukemia.

    Science.gov (United States)

    Eaves, C; Cashman, J; Eaves, A

    1998-12-01

    Over the last two decades considerable knowledge has been acquired about the distribution of cell types within the dominant leukemic (Ph+/BCR-ABL+) clone that results in human chronic myeloid leukemia (CML). Evidence is now growing to indicate that three key biological changes affecting the development of such clones are: (1) an increased probability of differentiation at the level of the most primitive leukemic stem cells; (2) an increased turnover rate of the leukemic progenitors at all stages of differentiation: and (3) their increased ability to survive under conditions of factor-deprivation. Such a model explains the long latent period for the development of CML as well as why normal stem cells may persist in large numbers but still fail to compete in contributing to the daily output of mature blood cells in patients with disease. The recent development of new genetic and transplant models of human CML may now allow the molecular basis of these biological disturbances to be delineated and more effective therapeutic strategies developed. PMID:9922073

  20. Adenosine Deaminase Activity in Chronic Lymphocytic Leukemia and Healthy Subjects

    Science.gov (United States)

    Ghaderi, Bayazid; Amini, Sabrieh; Maroofi, Farzad; Jalali, Chiya; Javanmardi, Mitra; Roshani, Daem; Abdi, Mohammad

    2016-01-01

    Background B cell chronic lymphocytic leukemia is one of the most frequent hematologic malignancies in the world. Cellular surface CD markers and serum Beta-2-microglobulin may be used as a prognostic tool in CLL patients. Objectives In the present study we introduce serum adenosine deaminase as a diagnostic marker in CLL. Materials and Methods Blood samples were collected from B-CLL and healthy subjects. White blood cell, red blood cell and platelet count and blood Erythrocyte sedimentation rate was recorded and serum Beta-2-microglobulin, Lactate dehydrogenase and total ADA enzyme activity were determined. Results Serum ADA activity was significantly higher in patients group than that of controls. ADA had a significant and direct correlation with B2M, WBC, LDH and ESR. However, there was not any relation between ADA and the stages of disease. Diagnostic cut-off, sensitivity and specificity of the serum ADA test were 27.97 U/L, 91% and 94%, respectively. Conclusions A higher ADA activity in patients group and its correlation with CLL markers were seen in our study. High diagnostic value of serum ADA in our study suggests that it might be considered as a useful screening tool among the other markers in CLL.

  1. Flavopiridol in chronic lymphocytic leukemia: a concise review.

    Science.gov (United States)

    Christian, Beth A; Grever, Michael R; Byrd, John C; Lin, Thomas S

    2009-01-01

    Patients with chronic lymphocytic leukemia (CLL) with high-risk cytogenetic features such as del(17p13) have limited treatment options and decreased overall survival. Dysfunction of p53 leads to resistance to fludarabine-based therapies. Cyclin-dependent kinase inhibitors (CDKi) are a novel class of agents that induce apoptosis in CLL cells independent of p53 mutational status. The synthetic flavone flavopiridol demonstrated promising in vitro activity in CLL. In initial phase I studies using a continuous infusion dosing schedule in a variety of malignancies, no clinical activity was observed. Detailed pharmacokinetic modeling led to the development of a novel dosing schedule designed to achieve target drug concentrations in vivo. In phase I testing, this dosing schedule resulted in acute tumor lysis syndrome (TLS) as the dose-limiting toxicity. With the implementation of a standardized protocol to prevent severe TLS, flavopiridol was administered safely, and responses were observed in heavily pretreated, fludarabine-refractory patients, cytogenetically high-risk patients, and patients with bulky lymphadenopathy. In a pharmacokinetic analysis, flavopiridol area under the plasma concentration-time curve (AUC) correlated with clinical response and cytokine release syndrome. Phase II studies are under way with encouraging preliminary results. Flavopiridol is currently under active investigation in combination with other agents and as a means to eradicate minimal residual disease in patients following cytoreductive chemotherapy. Several other investigational CDKi in preclinical and early clinical development are briefly discussed in this review. PMID:19778838

  2. Myeloid-derived suppressor cells in Chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Cesarina eGiallongo

    2015-05-01

    Full Text Available The suppression of the immune system create a permissive environment for development and progression of cancer. One population of immunosuppressive cells that have become the focus of intense study is myeloid derived suppressor cells (MDSCs, immature myeloid cells able to induce immune-escape, angiogenesis and tumor progression. Two different subpopulations have been identified and studied: granulocytic and monocytic MDSCs, with a different immunophenotype and immunosuppressive properties. Recently, an accumulation of both Gr-MDSCs and Mo-MDSCs cells has been found in the peripheral blood of chronic myeloid leukemia (CML patients. They are part of the tumor clone showing BCR/ABL expression. Imatinib therapy decreases both MDSCs and arginase 1 levels to normal ones. This review will focus on actual knowledge for human MDSCs and their immunosuppressive activity in CML patients with a critical attention to comparison of Gr-MDSCs and polymorphonuclear cells (PMNs. We will then suggest the monitoring of MDSCs in patients who have discontinued tyrosine kinase inhibitors (TKIs therapy to evaluate if their increase could correlate with disease relapse.

  3. TACI Expression and Signaling in Chronic Lymphocytic Leukemia

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    Antigoni Mamara

    2015-01-01

    Full Text Available TACI is a membrane receptor of BAFF and APRIL, contributing to the differentiation and survival of normal B cells. Although malignant B cells are also subjected on TACI signaling, there is a remarkable intradisease and interindividual variability of TACI expression in B-cell malignancies. The aim of our study was to explore the possible role of TACI signaling in the biology of chronic lymphocytic leukemia (CLL, including its phenotypic and clinical characteristics and prognosis. Ninety-four patients and 19 healthy controls were studied. CLL patients exhibited variable TACI expression, with the majority of cases displaying low to undetectable TACI, along with low to undetectable BAFF and increased APRIL serum levels compared to healthy controls. CLL cells with high TACI expression displayed a better survival capacity in vitro, when cultured with BAFF and/or APRIL. Moreover, TACI expression was positively correlated with the presence of monoclonal gammopathy and inversely with CD11c expression. Therefore, our study provides further evidence for the contribution of BAFF/APRIL signaling to CLL biology, suggesting also that TACI detection might be useful in the selection of patients for novel targeting therapeutic approaches.

  4. TACI Expression and Signaling in Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Mamara, Antigoni; Germenis, Anastasios E.; Kompoti, Maria; Palassopoulou, Maria; Mandala, Eudokia; Banti, Anastasia; Giannakoulas, Nikolaos

    2015-01-01

    TACI is a membrane receptor of BAFF and APRIL, contributing to the differentiation and survival of normal B cells. Although malignant B cells are also subjected on TACI signaling, there is a remarkable intradisease and interindividual variability of TACI expression in B-cell malignancies. The aim of our study was to explore the possible role of TACI signaling in the biology of chronic lymphocytic leukemia (CLL), including its phenotypic and clinical characteristics and prognosis. Ninety-four patients and 19 healthy controls were studied. CLL patients exhibited variable TACI expression, with the majority of cases displaying low to undetectable TACI, along with low to undetectable BAFF and increased APRIL serum levels compared to healthy controls. CLL cells with high TACI expression displayed a better survival capacity in vitro, when cultured with BAFF and/or APRIL. Moreover, TACI expression was positively correlated with the presence of monoclonal gammopathy and inversely with CD11c expression. Therefore, our study provides further evidence for the contribution of BAFF/APRIL signaling to CLL biology, suggesting also that TACI detection might be useful in the selection of patients for novel targeting therapeutic approaches. PMID:25950010

  5. The immunoglobulin genes: structure and specificity in chronic lymphocytic leukemia.

    Science.gov (United States)

    Tobin, Gerard

    2007-06-01

    The rearrangement of the immunoglobulin genes (IG) provides a large diversity of B-cell receptors conformations and allows the immune system to respond differently to foreign antigens. In chronic lymphocytic leukemia (CLL), there are a restricted number of stereotyped B-cell receptors rearranged by the tumor B-cells between CLL patients. These subsets with stereotyped receptors appear to have clinical implications, for example cases that rearrange the IGHV3-21 gene display poor clinical prognosis. The number of subsets with stereotyped receptors has been reported at a frequency of over 20% of CLL cases; however, the specificities of these receptors are still not clearly defined. Reactivity to epitopes from bacterial antigen, cytoskeleton components such as vimentin, and antigens on viable and apoptotic T-cell have been proposed. The role of antigen in CLL development is currently being more clearly defined with identification of stereotyped receptors, and their antigen specificity and the continued role antigen stimulation plays in CLL disease will be an important question in the future.

  6. Monoclonal Gammopathy of Undetermined Significance Disguised as Chronic Neutrophilic Leukemia

    Directory of Open Access Journals (Sweden)

    Monique A Hartley-Brown

    2010-02-01

    Full Text Available A 60-year-old woman with a medical history of diabetes mellitus, osteoporosis, peripheral vascular disease, and hypertension who was otherwise asymptomatic but continued showing elevated neutrophil levels sought a second opinion at our facility. Serum protein immunoelectrophoresis with immunofixation revealed an immunoglobulin A (IgA-κ monoclonal gammopathy concentration of 1305 mg/dL (normal 80-350 mg/dL but relatively normal concentrations of IgG of 840 mg/dL (620-1400 mg/dL and IgM of 36 mg/dL (45-250 mg/dL. Clonal analysis revealed a polyclonal expression pattern in all cell types analyzed. We concluded that our patient’s neutrophilia may have been due to the underlying monoclonal gammopathy. This is the first case in the literature of a patient with monoclonal gammopathy of undetermined significance presenting with neutrophilia, suggestive of chronic neutrophilic leukemia (CNL.  Patients with CNL have a poor prognosis; therefore, it is important to distinguish diagnostically between CNL and the less severe prognosis of monoclonal gammopathy of undetermined significance.

  7. Monoclonal Gammopathy of Undetermined Significance Disguised as Chronic Neutrophilic Leukemia

    Directory of Open Access Journals (Sweden)

    Monique A Hartley-Brown

    2010-02-01

    Full Text Available A 60-year-old woman with a medical history of diabetes mellitus, osteoporosis, peripheral vascular disease, and hypertension who was otherwise asymptomatic but continued showing elevated neutrophil levels sought a second opinion at our facility. Serum protein immunoelectrophoresis with immunofixation revealed an immunoglobulin A (IgA-κ monoclonal gammopathy concentration of 1305 mg/dL (normal 80-350 mg/dL but relatively normal concentrations of IgG of 840 mg/dL (620-1400 mg/dL and IgM of 36 mg/dL (45-250 mg/dL. Clonal analysis revealed a polyclonal expression pattern in all cell types analyzed. We concluded that our patient’s neutrophilia may have been due to the underlying monoclonal gammopathy. This is the first case in the literature of a patient with monoclonal gammopathy of undetermined significance presenting with neutrophilia, suggestive of chronic neutrophilic leukemia (CNL.  Patients with CNL have a poor prognosis; therefore, it is important to distinguish diagnostically between CNL and the less severe prognosis of monoclonal gammopathy of undetermined significance.

  8. Down-regulation of MicroRNAs 222/221 in Acute Myelogenous Leukemia with Deranged Core-Binding Factor Subunits

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    Matteo Brioschi

    2010-11-01

    Full Text Available Core-binding factor leukemia (CBFL is a subgroup of acutemyeloid leukemia (AML characterized by genetic mutations involving the subunits of the core-binding factor (CBF. The leukemogenesis model for CBFL posits that one, or more, gene mutations inducing increased cell proliferation and/or inhibition of apoptosis cooperate with CBF mutations for leukemia development. One of the most commonmutations associated with CBF mutations involves the KIT receptor. A high expression of KIT is a hallmark of a high proportion of CBFL. Previous studies indicate that microRNA (MIR 222/221 targets the 3′ untranslated region of the KIT messenger RNA and our observation that AML1 can bind the MIR-222/221 promoter, we hypothesized that MIR-222/221 represents the link between CBF and KIT. Here, we show that MIR-222/221 expression is upregulated after myeloid differentiation of normal bone marrow AC133+ stem progenitor cells. CBFL blasts with either t(8;21 or inv(16 CBF rearrangements with high expression levels of KIT (CD117 display a significantly lower level of MIR-222/221 expression than non-CBFL blasts. Consistently, we found that the t(8;21 AML1-MTG8 fusion protein binds the MIR-222/221 promoter and induces transcriptional repression of a MIR-222/221-LUC reporter. Because of the highly conserved sequence homology, we demonstrated concomitant MIR-222/221 down-regulation and KIT up-regulation in the 32D/WT1 mouse cell model carrying the AML1-MTG16 fusion protein. This study provides the first hint that CBFL-associated fusion proteins may lead to up-regulation of the KIT receptor by down-regulating MIR-222/221, thus explaining the concomitant occurrence of CBF genetic rearrangements and overexpression of wild type or mutant KIT in AML.

  9. Curcumin modulates chronic myelogenous leukemia exosomes composition and affects angiogenic phenotype via exosomal miR-21.

    Science.gov (United States)

    Taverna, Simona; Fontana, Simona; Monteleone, Francesca; Pucci, Marzia; Saieva, Laura; De Caro, Viviana; Cardinale, Valeria Giunta; Giallombardo, Marco; Vicario, Emanuela; Rolfo, Christian; Leo, Giacomo De; Alessandro, Riccardo

    2016-05-24

    Tumor derived exosomes are vesicles which contain proteins and microRNAs that mediate cell-cell communication and are involved in angiogenesis and tumor progression. Curcumin derived from the plant Curcuma longa, shows anticancer effects. Exosomes released by CML cells treated with Curcumin contain a high amount of miR-21 that is shuttled into the endothelial cells in a biologically active form. The treatment of HUVECs with CML Curcu-exosomes reduced RhoB expression and negatively modulated endothelial cells motility. We showed that the addition of CML control exosomes to HUVECs caused an increase in IL8 and VCAM1 levels, but Curcu-exosomes reversed these effects thus attenuating their angiogenic properties. This antiangiogenic effect was confirmed with in vitro and in vivo vascular network formation assays. SWATH analysis of the proteomic profile of Curcu-exosomes revealed that Curcumin treatment deeply changes their molecular properties, in particular, Curcumin induces a release of exosomes depleted in pro-angiogenic proteins and enriched in proteins endowed with anti-angiogenic activity. Among the proteins differential expressed we focused on MARCKS, since it was the most modulated protein and a target of miR-21. Taken together our data indicated that also Curcumin attenuates the exosome's ability to promote the angiogenic phenotype and to modulate the endothelial barrier organization. PMID:27050372

  10. Synthetic peptides derived from the Wilms' tumor 1 protein sensitize human T lymphocytes to recognize chronic myelogenous leukemia cells.

    Science.gov (United States)

    Müller, Ludmila; Knights, Ashley; Pawelec, Graham

    2003-01-01

    The Wilms' tumour 1 (WT1) molecule was screened in silico for the presence of 15-mer sequences predicted to bind HLA-DRB1(*)0401 (www.syfpeithi.de). Two peptides with the highest binding scores were synthesized (WT12e, PQQMGSDVRDLNALL and WT331, NKRYFKLSHLQMHSR). In vitro sensitization experiments using PBMC and the 15-mer peptides yielded peptide-specific responses against both WT12e and WT331 from six of seven healthy donors. Moreover, four of four different primary CML cell preparations were directly recognized by five different T cell lines, as assessed by IFN-gamma release. These responses were to a great extent blocked by anti-DR monoclonal antibody. These results suggest that WT1 peptides can be selected that are immunogenic for class II-restricted T-cell responses to native tumor cells, and indicate that they may find application in active immunotherapy of CML. PMID:12692522

  11. PR1-specific T cells are associated with unmaintained cytogenetic remission of chronic myelogenous leukemia after interferon withdrawal.

    Directory of Open Access Journals (Sweden)

    Shreya Kanodia

    Full Text Available BACKGROUND: Interferon-alpha (IFN induces complete cytogenetic remission (CCR in 20-25% CML patients and in a small minority of patients; CCR persists after IFN is stopped. IFN induces CCR in part by increasing cytotoxic T lymphocytes (CTL specific for PR1, the HLA-A2-restricted 9-mer peptide from proteinase 3 and neutrophil elastase, but it is unknown how CCR persists after IFN is stopped. PRINCIPAL FINDINGS: We reasoned that PR1-CTL persist and mediate CML-specific immunity in patients that maintain CCR after IFN withdrawal. We found that PR1-CTL were increased in peripheral blood of 7/7 HLA-A2+ patients during unmaintained CCR from 3 to 88 months after IFN withdrawal, as compared to no detectable PR1-CTL in 2/2 IFN-treated CML patients not in CCR. Unprimed PR1-CTL secreted IFNgamma and were predominantly CD45RA+/-CD28+CCR7+CD57-, consistent with functional naïve and central memory (CM T cells. Similarly, following stimulation, proliferation occurred predominantly in CM PR1-CTL, consistent with long-term immunity sustained by self-renewing CM T cells. PR1-CTL were functionally anergic in one patient 6 months prior to cytogenetic relapse at 26 months after IFN withdrawal, and in three relapsed patients PR1-CTL were undetectable but re-emerged 3-6 months after starting imatinib. CONCLUSION: These data support the hypothesis that IFN elicits CML-specific CM CTL that may contribute to continuous CCR after IFN withdrawal and suggest a role for T cell immune therapy with or without tyrosine kinase inhibitors as a strategy to prolong CR in CML.

  12. The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia

    OpenAIRE

    Levine, Ross L; Loriaux, Marc; Huntly, Brian J.P.; Loh, Mignon L.; Beran, Miroslav; Stoffregen, Eric; Berger, Roland; Clark, Jennifer J; Willis, Stephanie G; Kim T. Nguyen; Flores, Nikki J.; Estey, Elihu; Gattermann, Norbert; Armstrong, Scott; Look, A. Thomas

    2005-01-01

    Activating mutations in tyrosine kinases have been identified in hematopoietic and nonhematopoietic malignancies. Recently, we and others identified a single recurrent somatic activating mutation (JAK2V617F) in the Janus kinase 2 (JAK2) tyrosine kinase in the myeloproliferative disorders (MPDs) polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. We used direct sequence analysis to determine if the JAK2V617F mutation was present in acute myeloid leukemia (A...

  13. Miliaria-rash after neutropenic fever and induction chemotherapy for acute myelogenous leukemia Miliária 'rash' após neutropenia febril e quimioterapia de indução para a leucemia mielóide aguda

    Directory of Open Access Journals (Sweden)

    Tuyet A Nguyen

    2011-08-01

    Full Text Available Miliaria is a disorder of the eccrine sweat glands which occurs in conditions of increased heat and humidity. It can be associated with persistent febrile states as well as with certain drugs. We presented a 40 year-old female with myelodysplastic syndrome and progression to acute myelogenous leukemia who was admitted to the hospital for chemotherapy induction. The patient was treated with idarubicin and cytarabine. She became pancytopenic and developed neutropenic fever and was started on vancomycin and cefepime, but was persistently febrile with night sweats. Five days into her fevers, she developed diffuse, nonpruritic and fragile vesicles together with drenching nightsweats. The patient's exanthem was diagnosed as Miliaria crystallina, most probably induced by neutropenic fever and idarubucin exposureMiliária é uma desordem das glândulas sudoríparas écrinas, que ocorre em condições de aumento de calor e umidade. Miliária pode ser associada com estados febris persistentes bem como com certos medicamentos. Apresentamos o caso de uma mulher de 40 anos com síndrome mielodisplásica e progressão para leucemia mielóide aguda que foi admitida no hospital para quimioterapia de indução. A paciente foi tratada com idarrubicina e citarabina. Ela se tornou pancitopênica e desenvolveu neutropenia febril. Iniciou tratamento com vancomicina e cefepime, mas a febre com sudorese noturna continou. Cinco dias depois a paciente desenvolveu vesículas difusas, não pruríticas e frágeis juntamente com a persistência de sudorese noturna. O exantema do paciente foi diagnosticado como Miliária cristalina, provavelmente induzida por neutropenia febril e exposição a idarubucin

  14. Allogeneic bone marrow transplantation in children with acute myelogenous leukemia in first remission. Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) and the Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO).

    Science.gov (United States)

    Dini, G; Boni, L; Abla, O; Uderzo, C; Polchi, P; Locatelli, F; Di Bartolomeo, P; Arcese, W; Iori, A P; Rossetti, F

    1994-06-01

    Fifty-nine children, aged 1-15 years, with acute myelogenous leukemia (AML) received a bone marrow transplant (BMT) from an HLA-identical sibling (n = 57) or from an identical twin (n = 2), while in first remission (CR). These children represent, to the best of our knowledge, all children grafted in first CR in 11 Italian centers between 1980 and 1990. Patients were prepared with total body irradiation (TBI) plus cyclophosphamide (CY) (n = 50) or melphalan (n = 2) or with busulfan plus CY (n = 7). GVHD prophylaxis consisted of cyclosporin A (n = 48), methotrexate (n = 7) or cyclosporin and methotrexate (n = 2). Survivors have been followed for 21-137 months (median 59 months). Actuarial relapse-free survival was 58% at 66-137 months (95% confidence interval (CI) 44-72). Actuarial risk of relapse was 23% at 48 months (95% CI 10.9-34.8). Risk of non-relapse deaths was 33% in the period 1980-87 and 4% in the period 1988-90 (p = 0.02). In multivariate analysis patients with a blood cell count > 14 x 10(9)/l at diagnosis showed a lower relapse-free survival compared with patients with counts < 14 x 10(9)/l (p = 0.006). We could not detect an effect of FAB subtype, patient age, time to achieve remission or transplant-related variables, including year of BMT, on relapse-free survival. In conclusion, allogeneic marrow transplantation can achieve long-term relapse-free survival in over 50% of children with AML and should be considered as consolidation therapy if a matched sibling is available.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  16. Clinical efficacy of second generation tyrosine kinase inhibitor and 5-azacytidine combination in chronic myelogenous leukaemia in myeloid blast crisis.

    Science.gov (United States)

    Ghez, David; Micol, Jean-Baptiste; Pasquier, Florence; Auger, Nathalie; Saada, Véronique; Spentchian, Marc; Ianotto, Jean-Christophe; Bourhis, Jean-Henri; Bennaceur-Griscelli, Anelyse; Terré, Christine; Castaigne, Sylvie; Rigaudeau, Sophie; Rousselot, Philippe; de Botton, Stéphane

    2013-11-01

    Even in the tyrosine kinase inhibitors era, the prognosis of patients with chronic myeloid leukaemia in myeloid blast crisis remains dismal with few patients surviving longer than 6 months. Here we report the cases of 5 patients treated with the combination of 5-azacytidine and tyrosine kinase inhibitors for myeloid blast crisis CML. All patients achieved a complete haematological response including two with a complete cytogenetic and major molecular response. Two patients underwent an allogeneic stem cell transplantation. One died from relapse 34 months from diagnosis. The second is alive and free from disease at 11 months from diagnosis. The other 3 patients are still in complete haematological response after 15, 24 and 33 months of follow-up. These results suggest that the combination has a significant activity in myeloid blast crisis and may increase survival. PMID:23968731

  17. Vertigo as the First Sign of Chronic Myeloid Leukemia: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Rubén Martín-Hernández

    2013-01-01

    Full Text Available Acute vestibular deficit as the first sign of leukemia is extremely rare. The literature shows some cases of sudden hearing loss accompanied by instability and associated with hyperviscosity syndrome. We present the case of a patient who presents a harmonic vestibular deficit of the right ear. The complementary studies revealed an abnormally high level of leukocytes. A peripheral blood cytogenetic analysis is performed due to a high suspicion of leukemia, and the results show BCR/ABL fusion gene with a cut point in the M-BCR region, which confirms the diagnosis of chronic myeloid leukemia. In this case we detail the importance of taking hematological disorders into consideration in the differential diagnosis of patients with otoneurological symptoms, and we also review the etiopathogenic mechanisms, symptoms, diagnosis, and therapeutic options for chronic myeloid leukemia with sudden hearing loss and vertigo.

  18. Priapism – A Rare Presentation in Chronic Myeloid Leukemia: Case Report

    OpenAIRE

    Nerli, Rajendra B.; Magdum, Prasad V.; Hiremath, Siddayya C.; Amey Y. Patil; Pai, Suvarna V.; Handigund, Rajeshwari S.; Hiremath, M. B.

    2015-01-01

    Priapism is a complication rarely seen in leukemia. We report a 19-year-old man presented with persistent painful erection of penis for over 24 hours at home. The patient had underwent immediate irrigation and decompression of priapism by urologist at emergency services of the hospital. This approach resulted in a flaccid penis later. During hospitalization, peripheral blood smear and bone marrow aspiration confirmed the diagnosis of chronic myeloid leukemia.

  19. Priapism – A Rare Presentation in Chronic Myeloid Leukemia: Case Report

    Directory of Open Access Journals (Sweden)

    Rajendra B. Nerli

    2016-01-01

    Full Text Available Priapism is a complication rarely seen in leukemia. We report a 19-year-old man presented with persistent painful erection of penis for over 24 hours at home. The patient had underwent immediate irrigation and decompression of priapism by urologist at emergency services of the hospital. This approach resulted in a flaccid penis later. During hospitalization, peripheral blood smear and bone marrow aspiration confirmed the diagnosis of chronic myeloid leukemia.

  20. Essential role for telomerase in chronic myeloid leukemia induced by BCR-ABL in mice

    OpenAIRE

    Vicente-Dueñas, Carolina; Barajas-Diego, Marcos; Romero-Camarero, Isabel; González-Herrero, Inés; Flores, Teresa; Sánchez García, Isidro

    2012-01-01

    The telomerase protein is constitutively activated in malignant cells from many patients with cancer, including the chronic myeloid leukemia (CML), but whether telomerase is essential for the pathogenesis of this disease is not known. Here, we used telomerase deficient mice to determine the requirement for telomerase in CML induced by BCR-ABL in mouse models of CML. Loss of one telomerase allele or complete deletion of telomerase prevented the development of leukemia induced by BCR-ABL. Howev...

  1. Priapism - A Rare Presentation in Chronic Myeloid Leukemia: Case Report.

    Science.gov (United States)

    Nerli, Rajendra B; Magdum, Prasad V; Hiremath, Siddayya C; Patil, Amey Y; Pai, Suvarna V; Handigund, Rajeshwari S; Hiremath, M B

    2016-01-01

    Priapism is a complication rarely seen in leukemia. We report a 19-year-old man presented with persistent painful erection of penis for over 24 hours at home. The patient had underwent immediate irrigation and decompression of priapism by urologist at emergency services of the hospital. This approach resulted in a flaccid penis later. During hospitalization, peripheral blood smear and bone marrow aspiration confirmed the diagnosis of chronic myeloid leukemia. PMID:26793565

  2. Unusual case of bancroftian filariasis co-existing with chronic myeloid leukemia

    OpenAIRE

    Mallika Kinger; Preeti Rihal Chakrabarti; Surabhi Sharma; Priyanka Kiyawat

    2014-01-01

    Filariasis, a tropical parasite infection, is a common public health problem in the Indian sub-continent. Occurrence of filariasis with chronic myeloid leukemia (CML) is unusual though there are case reports of leishmaniasis, malaria, and other vector-borne diseases seen in association with leukemias. Filariasis co-existing with CML has not been documented to the best of our knowledge and hence definitely needs a space in literature. We report an incidental finding of bancroftian filariasis i...

  3. B cell receptor pathway in chronic lymphocytic leukemia: specific role of CC-292

    OpenAIRE

    Arnason JE; Brown JR

    2014-01-01

    Jon E Arnason,1 Jennifer R Brown21Beth Israel Deaconess Medical Center, 2CLL Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USAAbstract: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. The current treatment paradigm involves the use of chemoimmunotherapy, when patients develop an indication for therapy. With this strategy, a majority of patients will obtain a remission, though cure remains elusive. While treatabl...

  4. Triple cancer: chronic lymphocytic leukemia with bladder and prostate carcinoma.

    Science.gov (United States)

    Gajendra, Smeeta; Sharma, Rashi; Sahoo, Manas Kumar

    2015-08-01

    B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a common lymphoproliferative disorder with an increased risk of developing subsequent neoplasms of epithelial and mesenchymal origin. The decreased immunity and B-cell dysfunction in CLL probably accounts for this emergence of second malignancies. We report a case of synchronous bladder transitional cell carcinoma (TCC) and prostatic carcinoma with CLL. A 74-year-old male who underwent transurethral resection of the prostate (TURP) for benign prostatic hyperplasia 2 years before, presented with recurrent urinary tract infection. Peripheral blood smear revealed leukocytosis with absolute lymphocytosis (absolute lymphocyte count: 37870 cells/mm³). Flow cytometric immunophenotyping revealed 75% abnormal lymphoid cells which were positive for CD 19, CD5, CD23, CD22, CD200, CD20 (moderate) with lambda light chain restriction and negative for CD3, CD10, FMC7, CD38, CD138, IgM, CD103, CD123. F Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) showed increased metabolic activity of the left lateral wall of the urinary bladder extending to the left UV junction, adjacent part of trigone and bladder neck region along with multiple heterogeneous enhancing areas with increased FDG avidity within the prostate. Transurethral resection of the bladder tumour by cystoscopy was performed. Histopathology showed high grade, muscle invasive urothelial carcinoma. Due to presence of uptake in the prostate, transurethral resection of the prostate was done and histopathology revealed adenocarcinoma of prostate (prostate specific antigen- positive), Gleason grade III+III and Gleason score 6. A high index of suspicion is required to detect synchronous and metachronous malignancies. Ancillary studies such as immunohistochemistry, flow cytometry and PET/CT are often essential for detection and an accurate diagnosis. PMID:26277675

  5. Recurrent mutations refine prognosis in chronic lymphocytic leukemia.

    Science.gov (United States)

    Baliakas, P; Hadzidimitriou, A; Sutton, L-A; Rossi, D; Minga, E; Villamor, N; Larrayoz, M; Kminkova, J; Agathangelidis, A; Davis, Z; Tausch, E; Stalika, E; Kantorova, B; Mansouri, L; Scarfò, L; Cortese, D; Navrkalova, V; Rose-Zerilli, M J J; Smedby, K E; Juliusson, G; Anagnostopoulos, A; Makris, A M; Navarro, A; Delgado, J; Oscier, D; Belessi, C; Stilgenbauer, S; Ghia, P; Pospisilova, S; Gaidano, G; Campo, E; Strefford, J C; Stamatopoulos, K; Rosenquist, R

    2015-02-01

    Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (P<0.0001) in 889 treatment-naive Binet stage A cases. In multivariate analysis (n=774), SF3B1 mutations and TP53ab along with del(11q) and U-CLL, but not NOTCH1 mutations, retained independent significance. Importantly, TP53ab and SF3B1 mutations had an adverse impact even in U-CLL. In conclusion, we support the clinical relevance of novel recurrent mutations in CLL, highlighting the adverse impact of SF3B1 and TP53 mutations, even independent of IGHV mutational status, thus underscoring the need for urgent standardization/harmonization of the detection methods.

  6. Chronic Myelomonocytic Leukemia with t(3;9)(p21;p13) as a Sole Abnormal Appearance: One Case Report

    Institute of Scientific and Technical Information of China (English)

    Ji-hong ZHANG; Li-jun GUAN; Yun-xiu WANG; Ying-chun ZHENG; Nan ZHANG; Hai-xia TONG

    2010-01-01

    @@ Introduction Chronic myelomonocytic leukemia, (CMML) is a clinically rare chronic myeloid leukemia, with an incidence rate of about 1-2/100,000/year, and the age of the predominant cases is over 60 years. The median age of onset is 65-70 years, and the ratio of the incidence between male and female is about 1.5 : 3.1.

  7. p53 mutations in human lymphoid malignancies: Association with Burkitt lymphoma and chronic lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Gaidano, G.; Ballerini, P.; Gong, J.Z.; Inghirami, G.; Knowles, D.M.; Dalla-Favera, R. (Columbia Univ., New York, NY (United States)); Neri, A, (Columbia Univ., New York, NY (United States) Centro Malattie del Sangue G. Marcora, Milan (Italy)); Newcomb, E.W. (New York Univ. School of Medicine, New York (United States)); Magrath, I.T. (National Cancer Institute, Bethesda, MD (United States))

    1991-06-15

    The authors have investigated the frequency of p53 mutations in B- and T-cell human lymphoid malignancies, including acute lymphoblastic leukemia, the major subtypes of non-Hodgkin lymphoma, and chronic lymphocytic leukemia. p53 exons 5-9 were studied by using genomic DNA from 197 primary tumors and 27 cell lines by single-strand conformation polymorphism analysis and by direst sequencing of PCR-amplified fragments. Mutations were found associated with (i) Burkitt lymphoma (9/27 biopsoes; 17/27 cell lines) and its leukemic counterpart L{sub 3}-type B-cell acute lymphoblastic leukemia (5/9), both of which also carry activated c-myc oncogenes, and (ii) B-cell chronic lymphocytic leukemia (6/40) and, in particular, its stage of progression known as Richter's transformation (3/7). Mutations were not found at any significant frequency in other types of non-Hodgkin lymphoma or acute lymphoblastic leukemia. In many cases, only the mutated allele was detectable, implying loss of the normal allele. These results suggest that (1) significant differences in the frequency of p53 mutations are present among subtypes of neoplasms derived from the same tissue; (2) p53 may play a role in tumor progression in B-cell chronic lymphocytic leukemia; (3) the presence of both p53 loss/inactivation and c-myc oncogene activation may be important in the pathogenesis of Burkitt lymphoma and its leukemia form L{sub 3}-type B-cell acute lymphoblastic leukemia.

  8. SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Li; Weng, Wei; Sun, Zhi-Xin; Fu, Xian-Jie; Ma, Jun, E-mail: majuntongrensh1@126.com; Zhuang, Wen-Fang, E-mail: wenfangzhuangmd@163.com

    2015-05-15

    Previous studies have identified sphingosine kinase 1 (SphK1) as a potential drug target for treatment of acute myeloid leukemia (AML). In the current study, we investigated the potential anti-leukemic activity of a novel and specific SphK1 inhibitor, SKI-II. We demonstrated that SKI-II inhibited growth and survival of human AML cell lines (HL-60 and U937 cells). SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, and concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells. Conversely, exogenously-added S1P protected against SKI-II-induced cytotoxicity, while cell permeable short-chain ceramide (C6) aggravated SKI-II's lethality against AML cells. Notably, SKI-II induced potent apoptotic death in primary human AML cells, but was generally safe to the human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. In vivo, SKI-II administration suppressed growth of U937 leukemic xenograft tumors in severe combined immunodeficient (SCID) mice. These results suggest that SKI-II might be further investigated as a promising anti-AML agent. - Highlights: • SKI-II inhibits proliferation and survival of primary and transformed AML cells. • SKI-II induces apoptotic death of AML cells, but is safe to normal PBMCs. • SKI-II is more efficient than two known SphK1 inhibitors in inhibiting AML cells. • SKI-II inhibits SphK1 activity, while increasing ceramide production in AML cells. • SKI-II dose-dependently inhibits U937 xenograft growth in SCID mice.

  9. Analysis of low Z elements in serum of patients with leukemias by SRTXRF

    International Nuclear Information System (INIS)

    Leukemia is a disease that occurs all over the world. Leukemia is a type of cancer. All cancers begin in cells, which make up blood and other tissues. Normally, cells grow and divide to form new cells as the body needs them. When cells grow old, they die, and new cells take their place. Sometimes this orderly process goes wrong. New cells form when the body does not need them, and old cells do not die when they should. Leukemia is a kind of cancer that begins in blood cells. There are four common types of leukemia: Chronic Myelogenous Leukemia (CML), Acute Myelogenous Leukemia (AML), Chronic Lymphocytic Leukemia (CLL) and Acute Lymphocytic Leukemia (ALL). In this work, low Z elements were determined in serum of patients with four groups of leukemia (CML, AML, CLL and ALL) and control group (CG) or healthy subjects using Total Reflection X-Ray Fluorescence induced by Synchrotron Radiation (SRTXRF). We studied thirty patients - male gender and feminine gender - with ages ranging from 18 to 60 years, suffering from CML, AML, CLL, ALL and thirty healthy volunteers aged 18 to 60 years. All the serum samples were collected from people who live in the urban area of Rio de Janeiro City/Brazil. All of them were submitted to medical history. This study was performed with the approval of the ethics committee. It was possible to determine the elemental concentrations of the following six elements: Na, P, S, Cl, K and Ca. By using t-test it could be seen significant differences (α = 0.05) between groups of healthy subjects and four groups of leukemia. The t- test showed real differences among the elemental concentrations. Thus, our findings indicate that the elements can be directly related to the biochemical processes in leukemias. The significant differences found between the groups may be indicators of these diseases. This could help biomedical field with regard to early diagnosis and improved medical treatment. (author)

  10. Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia

    Science.gov (United States)

    2016-02-20

    Leukemias; Acute Myeloid Leukemia (AML); Acute Lymphocytic Leukemia (ALL); Adult T Cell Leukemia (ATL); Chronic Myeloid Leukemia (CML-BP); Chronic Lymphocytic Leukemia (CLL); Myelodysplastic Syndrome (MDS); Chronic Myelomonocytic Leukemia (CMML)

  11. Update in the management of chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Lin Thomas S

    2009-07-01

    Full Text Available Abstract Advances in the treatment of chronic lymphocytic leukemia (CLL have improved initial overall response (OR rates, complete response (CR rates and progression free survival (PFS. Despite these advances, CLL remains incurable with standard therapies. Thus, there remains a need for more effective therapies in both the upfront and relapsed setting, particularly for patients with high-risk cytogenetic abnormalities such as del(11q22 and del(17p13. The 2008 American Society of Hematology (ASH Annual Meeting featured several presentations which highlighted the ongoing clinical advances in CLL. The benefit of adding rituximab to purine analog therapy in the upfront setting was demonstrated by a large randomized study which showed that the addition of rituximab to fludarabine and cyclophosphamide (FCR significantly improved OR, CR and PFS. The improvement in PFS directly resulted from an improved ability to eliminate minimal residual disease (MRD in the peripheral blood, highlighting the importance of MRD eradication. However, a multi-center study suggested that the high CR rates to chemoimmunotherapy regimens such as FCR obtained in academic centers may not be reproducible when the same regimens are given in the community setting. The immunomodulatory drug lenalidomide is active in relapsed high-risk CLL, but two studies of lenalidomide in previously untreated CLL patients failed to achieve a CR and were associated with significant tumor lysis, tumor flare and hematologic toxicity. In the relapsed setting, a combination study of the bifunctional alkylator bendamustine and rituximab (BR demonstrated a high OR rate in patients with del(11q22 and del(17p13, indicating that further studies to define's bendamustine activity are warranted in high-risk CLL. Similarly, the CDK inhibitor flavopiridol demonstrated significant clinical activity and durable remissions in heavily treated, refractory CLL patients with high-risk cytogenetic features and bulky

  12. Genetic features of B-cell chronic lymphocytic leukemia.

    Science.gov (United States)

    Stilgenbauer, S; Lichter, P; Döhner, H

    2000-03-01

    The genetic features of B-cell chronic lymphocytic leukemia (CLL) are currently being reassessed by molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH). Conventional cytogenetic studies by chromosome banding are difficult in CLL mainly because of the low in vitro mitotic activity of the tumor cells, which leads to poor quantity and quality of metaphase spreads. Molecular genetic analyses are limited because candidate genes are known for only a few chromosomal aberrations that are observed in CLL. FISH was found to be a powerful tool for the genetic analysis of CLL as it overcomes both the low mitotic activity of the CLL cells and the lack of suitable candidate genes for analysis. Using FISH, the detection of chromosomal aberrations can be performed at the single cell level in both dividing and non-dividing cells, thus circumventing the need of metaphase preparations from tumor cells. Probes for the detection of trisomies, deletions and translocation breakpoints can be applied to the regions of interest with the growing number of clones available from genome-wide libraries. Using the interphase cytogenetic FISH approach with a disease specific set of probes, chromosome aberrations can be found in more than 80% of CLL cases. The most frequently observed abnormalities are losses of chromosomal material, with deletions in band 13q14 being the most common, followed by deletions in 11q22-q23, deletions in 17p13 and deletions in 6q21. The most common gains of chromosomal material are trisomies 12q, 8q and 3q. Translocation breakpoints, in particular involving the immunoglobulin heavy chain locus at 14q32, which are frequently observed in other types of non-Hodgkin's lymphoma, are rare events in CLL. Genes affected by common chromosome aberrations in CLL appear to be p53 in cases with 17p deletion and ataxia telangiectasia mutated (ATM), which is mutated in a subset of cases with 11q22-q23 aberrations. However, for the other frequently

  13. Progress in the Studies of Acute Myelogenous Leukemia Stem Cell--Review%急性髓系白血病干细胞的研究进展

    Institute of Scientific and Technical Information of China (English)

    崔久嵬; 张学敏; 王冠军

    2003-01-01

    急性髓系白血病(AML)细胞群是由不同分化阶段的白血病细胞组成,其中最原始的细胞为白血病干细胞(leukemia stem cell, LSC).虽然LSC所占比例极少,但仅其具有维持白血病细胞克隆的作用.AML的恶性转化发生在干细胞水平,这种发生恶性转化的干细胞的细胞和分子遗传学改变决定了白血病细胞克隆的分化特点,从而形成不同亚型的AML. LSC与正常造血干细胞(hematopoietic stem cell, HSC)有许多相似之处,它具有自我更新能力和有限的分化潜能,同时又具有其自身独特的特征.LSC具有某些特殊的细胞表面标志,如CD90-, CD117-, CD123+.与正常的HSC相比,肿瘤抑制性蛋白-死亡相关蛋白激酶和干扰素调节因子1在LSC中高表达.与相对分化的白血病细胞相比,LSC主要处于G0期, 其对常规化疗药物无效,因此LSC是白血病复发的根源.虽然LSC具有耐药的特点,但经合适的刺激如蛋白酶体抑制剂MG-132的处理,LSC比正常HSC更易于凋亡.本文将近年来对LSC的细胞和分子生物学方面研究的进展进行综述,为白血病发病机制及治疗策略的探讨提供新的思路.

  14. O tratamento da Leucemia Mielóide Crônica com mesilato de imatinibe Therapy of Chronic Myeloid Leukemia with imatinib mesylate

    Directory of Open Access Journals (Sweden)

    Vaneuza M. Funke

    2008-04-01

    Full Text Available O mesilato de imatinibe é atualmente o tratamento de escolha para pacientes com Leucemia mielóide Crônica (LMC recém-diagnosticados. Desde os primeiros estudos clínicos em 1998 até o estudo IRIS, que comparou o uso em primeira linha de imatinibe com interferon + ara-C, esta droga vem se consolidando em segurança e eficácia. Ainda há, entretanto questionamentos sobre a melhor dose inicial, a identificação dos pacientes que mais se beneficiariam e a melhor abordagem frente a respostas sub-ótimas e resistência. Os principais estudos clínicos publicados com mesilato de imatinibe são revisados no presente artigo, e discutidos sob a perspectiva da realidade brasileira.Imatinib mesylate is currently the gold-standard therapy for patients with newly diagnosed Chronic Myelogenous Leukemia. From the clinical trials in 1998 to the IRIS study, which compared first line imatinib treatment with interferon and low dose ara-C, this drug has been consolidated in regards to its safety and efficacy. There are still some questions to answer. Which would be the best initial dose? Are there any patients who benefit more than others? What is the best approach to suboptimal response and resistance? The most important published clinical studies are reviewed in the current article and discussed from a Brazilian perspective.

  15. Forced Expression of Cyclin-Dependent Kinase 6 Confers Resistance of Pro-B Acute Lymphocytic Leukemia to Gleevec Treatment▿ †

    OpenAIRE

    Kuo, Tracy C.; Chavarria-Smith, Joseph E.; Huang, Dan; Schlissel, Mark S.

    2011-01-01

    The gene encoding c-ABL, a nonreceptor protein tyrosine kinase, is involved in a chromosomal translocation resulting in expression of a BCR-Abl fusion protein that causes most chronic myelogenous and some acute lymphocytic leukemias (CML and ALL) in humans. The Abelson murine leukemia virus (A-MuLV) expresses an alternative form of c-Abl, v-Abl, that transforms murine pro-B cells, resulting in acute leukemia and providing an experimental model for human disease. Gleevec (STI571) inhibits the ...

  16. Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Berthou Christian

    2010-12-01

    Full Text Available Abstract Background We previously reported that allanxanthone C and macluraxanthone, two xanthones purified from Guttiferae trees, display in vitro antiproliferative and proapoptotic activities in leukemic cells from chronic lymphocytic leukemia (CLL and leukemia B cell lines. Results Here, we investigated the in vivo therapeutic effects of the two xanthones in a xenograft murine model of human CLL, developed by engrafting CD5-transfected chronic leukemia B cells into SCID mice. Treatment of the animals with five daily injections of either allanxanthone C or macluraxanthone resulted in a significant prolongation of their survival as compared to control animals injected with the solvent alone (p = 0.0006 and p = 0.0141, respectively. The same treatment of mice which were not xenografted induced no mortality. Conclusion These data show for the first time the in vivo antileukemic activities of two plant-derived xanthones, and confirm their potential interest for CLL therapy.

  17. Reduced Intensity Preparative Regimen Followed by Stem Cell Transplant (FAB)

    Science.gov (United States)

    2016-03-29

    Myelodysplastic and Myeloproliferative Disorders; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; Multiple Myeloma; Plasma Cell Dyscrasia; Lymphoproliferative Disorders; Hematologic Diseases

  18. Not all IGHV3-21 chronic lymphocytic leukemias are equal

    DEFF Research Database (Denmark)

    Baliakas, Panagiotis; Agathangelidis, Andreas; Hadzidimitriou, Anastasia;

    2015-01-01

    An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue...

  19. Chronic neutrophilic leukemia 2016: Update on diagnosis, molecular genetics, prognosis, and management.

    Science.gov (United States)

    Elliott, Michelle A; Tefferi, Ayalew

    2016-03-01

    Chronic neutrophilic leukemia (CNL) is a potentially aggressive myeloproliferative neoplasm, for which current WHO diagnostic criteria include leukocytosis of ≥25 × 10(9) /L (of which >80% are neutrophils) and with strategies, but the foundations for these are strengthening. Am. J. Hematol. 91:342-349, 2016. © 2015 Wiley Periodicals, Inc. PMID:26700908

  20. Not all IGHV3-21 chronic lymphocytic leukemias are equal: Prognostic considerations

    NARCIS (Netherlands)

    P. Baliakas (P.); A. Agathangelidis (Andreas); A. Hadzidimitriou (A.); L.-A. Sutton (L.); E. Minga (Evangelia); A. Tsanousa (Athina); L. Scarfó (L.); Z. Davis (Zadie); X.-J. Yan (Xiao-Jie); T. Shanafelt (Tait); K. Plevova (K.); Y. Sandberg (Yorick); F.J. Vojdeman (Fie Juhl); M. Boudjogra (Myriam); T. Tzenou (T.); M. Chatzouli (Maria); C.C. Chu (Charles C.); S. Veronese (Silvio); A. Gardiner (Anne); A. Mansouri (Ahmed); O. Smedby; L.B. Pedersen (Lone Bredo); D. Moreno (Denis); K. van Lom (Kirsten); V. Giudicelli (Veronique); H.S. Francova (Hana Skuhrova); F. Nguyen-Khac (Florence); P. Panagiotidis (P.); G. Juliusson (Gunnar); L. Angelis (Lefteris); C. Anagnostopoulos (Constantinos); M.-P. Lefranc (Marie-Paule); M. Facco (Monica); L. Trentin (Livio); M. Catherwood (M.); M. Montillo (Marco); C.H. Geisler (Christian); A.W. Langerak (Ton); D. Pospisilova (Dagmar); N. Chiorazzi (Nicholas); D.G. Oscier (David Graham); D.F. Jelinek (Diane F.); N. Darzentas (N.); C. Belessi (C.); F. Davi; P. Ghia (Paolo); R. Rosenquist (R.); K. Stamatopoulos (K.)

    2015-01-01

    textabstractAn unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised thi

  1. Hepatitis B virus reactivation in a chronic myeloid leukemia patient treated with imatinib mesylate

    Institute of Scientific and Technical Information of China (English)

    WANG Ya-dan; CUI Guo-hui; LI Mian; GOWREA Bhuveshwarnath; XIA Jia; HU Yu

    2012-01-01

    Imatinib mesylate is a molecular targeted agent for treating chronic myeloid leukemia (CML) and gastrointestinal stromal tumor.Although imatinib mesylate is not regarded as an immunosuppressive agent,few studies have also shown that it may impair immune response.In this report,we present a case of transient hepatitis B virus (HBV) reactivation during imatinib mesylate treatment for CML.

  2. Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia

    NARCIS (Netherlands)

    Deenik, Wendy; Janssen, Jeroen J. W. M.; van der Holt, Bronno; Verhoef, Gregor E. G.; Smit, Willem M.; Kersten, Marie Jose; Daenen, Simon M. G. J.; Verdouck, Leo F.; Ferrant, Augustin; Schattenberg, Anton V. M. B.; Sonneveld, Pieter; Kooy, Marinus van Marwijk; Wittebol, Shulamit; Willemze, Roelof; Wijermans, Pierre W.; Beverloo, H. Berna; Lowenberg, Bob; Valk, Peter J. M.; Ossenkoppele, Gert J.; Cornelissen, Jan J.

    2010-01-01

    Background In order to improve the molecular response rate and prevent resistance to treatment, combination therapy with different dosages of imatinib and cytarabine was studied in newly diagnosed patients with chronic myeloid leukemia in the HOVON-51 study. Design and Methods Having reported feasib

  3. Patient- versus physician-reporting of symptoms and health status in chronic myeloid leukemia

    NARCIS (Netherlands)

    F. Efficace; G. Rosti; N. Aaronson; F. Cottone; E. Angelucci; S. Molica; M. Vignetti; F. Mandelli; M. Baccarani

    2013-01-01

    The main objective of this study was to compare the reporting of health status and symptom severity, for a set of core symptoms related to imatinib therapy, between chronic myeloid leukemia patients and their treating physicians. Patients were asked to complete a questionnaire including questions on

  4. Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Gunnarsson, Rebeqa; Mansouri, Larry; Isaksson, Anders;

    2011-01-01

    High-resolution genomic microarrays enable simultaneous detection of copy-number aberrations such as the known recurrent aberrations in chronic lymphocytic leukemia [del(11q), del(13q), del(17p) and trisomy 12], and copy-number neutral loss of heterozygosity. Moreover, comparison of genomic...

  5. The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia

    OpenAIRE

    Brown, Jennifer R; Barrientos, Jacqueline C.; Barr, Paul M.; Flinn, Ian W.; Burger, Jan A.; Tran, Anh; Clow, Fong; James, Danelle F; Graef, Thorsten; Friedberg, Jonathan W.; Rai, Kanti; O’Brien, Susan

    2015-01-01

    Ibrutinib was well tolerated when administered with BR CIT in previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma.Ibrutinib added to CIT was associated with a high degree of clinical activity that compares favorably to historical reports of CIT alone.

  6. Imatinib-dependent tyrosine phosphorylation profiling of Bcr-Abl-positive chronic myeloid leukemia cells

    OpenAIRE

    Preisinger, C.; Schwarz, J. P.; Bleijerveld, O.B.; et al

    2012-01-01

    Bcr-Abl is the major cause and pathogenetic principle of chronic myeloid leukemia (CML). Bcr-Abl results from a chromosomal translocation that fuses the bcr and abl genes, thereby generating a constitutively active tyrosine kinase, which stimulates several signaling networks required for proliferation and survival. peer-reviewed

  7. Abnormal distribution of CD8 subpopulation in B-chronic lymphocytic leukemia identified by flow cytometry

    NARCIS (Netherlands)

    Terstappen, L.W.M.M.; Grooth, de B.G.; Berkel, van W.; Napel, ten C.H.H.

    1988-01-01

    We studied the occurrence of T-cell subpopulations for patients with B-cell chronic lymphocytic leukemia. The CD8+ population was divided into CD8+ suppressor (CD8a+) and CD8+ cytotoxic (CD8b+) lymphocytes using difference in orthogonal light scattering. Average CD4+/CD8+ratios determined for all p

  8. B-Cell Receptor Epitope Recognition Correlates With the Clinical Course of Chronic Lymphocytic Leukemia

    NARCIS (Netherlands)

    Binder, Mascha; Mueller, Fabian; Jackst, Antje; Lechenne, Barbara; Pantic, Milena; Bacher, Ulrike; Eulenburg, Christine Zu; Veelken, Hendrik; Mertelsmann, Roland; Pasqualini, Renata; Arap, Wadih; Trepel, Martin

    2011-01-01

    BACKGROUND: B-cell receptors (BCRs) and their recognition of specific epitopes may play a pivotal role in the development and progression of chronic lymphocytic leukemia (CLL). In this study, the authors set up a model system to explore epitope reactivity and its clinical relevance in CLL. METHODS:

  9. Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Strefford, J C; Sutton, L-A; Baliakas, P;

    2013-01-01

    Recent studies have revealed recurrent mutations of the NOTCH1, SF3B1 and BIRC3 genes in chronic lymphocytic leukemia (CLL), especially among aggressive, chemorefractory cases. Nevertheless, it is currently unknown whether their presence may differ in subsets of patients carrying stereotyped B...

  10. Current status of imatinib as frontline therapy for chronic myeloid leukemia.

    Science.gov (United States)

    Marin, David

    2010-10-01

    Imatinib is remarkably effective in treating newly diagnosed patients with chronic myeloid leukemia (CML) in chronic phase. However, at 5 years more than one third of the patients have abandoned the medication on account of side effects, lack of efficacy, or progression. Here we review the current results with imatinib, the prognostic factors for response, and issues associated with long-term treatment with imatinib such as pregnancy, adherence to therapy, and complete molecular responses.

  11. A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Seymour, J F; Kim, D W; Rubin, E;

    2014-01-01

    achieved major hematologic response. The most common adverse event (AE) was neutropenia (50%). The most common grade 3/4 AEs were neutropenia (46%) and febrile neutropenia (35%). MK-0457 demonstrated minimal efficacy and only at higher, intolerable doses; lower doses were tolerated and no unexpected...

  12. Clinical significance of microRNAs in chronic and acute human leukemia.

    Science.gov (United States)

    Yeh, Chien-Hung; Moles, Ramona; Nicot, Christophe

    2016-01-01

    Small non-coding microRNAs (miRNAs) are epigenetic regulators that target specific cellular mRNA to modulate gene expression patterns and cellular signaling pathways. miRNAs are involved in a wide range of biological processes and are frequently deregulated in human cancers. Numerous miRNAs promote tumorigenesis and cancer progression by enhancing tumor growth, angiogenesis, invasion and immune evasion, while others have tumor suppressive effects (Hayes, et al., Trends Mol Med 20(8): 460-9, 2014; Stahlhut and Slack, Genome Med 5 (12): 111, 2013). The expression profile of cancer miRNAs can be used to predict patient prognosis and clinical response to treatment (Bouchie, Nat Biotechnol 31(7): 577, 2013). The majority of miRNAs are intracellular localized, however circulating miRNAs have been detected in various body fluids and represent new biomarkers of solid and hematologic cancers (Fabris and Calin, Mol Oncol 10(3):503-8, 2016; Allegra, et al., Int J Oncol 41(6): 1897-912, 2012). This review describes the clinical relevance of miRNAs, lncRNAs and snoRNAs in the diagnosis, prognosis and treatment response in patients with chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) and acute adult T-cell leukemia (ATL). PMID:27179712

  13. Leukemias

    Directory of Open Access Journals (Sweden)

    Riccardo Masetti

    2011-01-01

    Full Text Available Acute leukemia is the most common type of childhood and adolescence cancer, characterized by clonal proliferation of variably differentiated myeloid or lymphoid precursors. Recent insights into the molecular pathogenesis of leukemia have shown that epigenetic modifications, such as deacetylation of histones and DNA methylation, play crucial roles in leukemogenesis, by transcriptional silencing of critical genes. Histone deacetylases (HDACs are potential targets in the treatment of leukaemia, and, as a consequence, inhibitors of HDACs (HDIs are being studied for therapeutic purposes. HDIs promote or enhance several different anticancer mechanisms, such as apoptosis, cell cycle arrest, and cellular differentiation and, therefore, are in evidence as promising treatment for children and adolescents with acute leukemia, in monotherapy or in association with other anticancer drugs. Here we review the main preclinical and clinical studies regarding the use of HDIs in treating childhood and adolescence leukemia.

  14. p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia.

    OpenAIRE

    Gaidano, G; Ballerini, P.; Gong, J. Z.; Inghirami, G.; Neri, A.; Newcomb, E W; Magrath, I. T.; Knowles, D M; Dalla-Favera, R

    1991-01-01

    We have investigated the frequency of p53 mutations in B- and T-cell human lymphoid malignancies, including acute lymphoblastic leukemia, the major subtypes of non-Hodgkin lymphoma, and chronic lymphocytic leukemia. p53 exons 5-9 were studied by using genomic DNA from 197 primary tumors and 27 cell lines by single-strand conformation polymorphism analysis and by direct sequencing of PCR-amplified fragments. Mutations were found associated with (i) Burkitt lymphoma (9/27 biopsies; 17/27 cell l...

  15. A Study of Withdrawal of Immunosuppression and Donor Lymphocyte Infusions Following Allogeneic Transplant for Pediatric Hematologic Malignancies

    Science.gov (United States)

    2016-05-18

    Acute Leukemia; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Biphenotypic Leukemia; Pre-leukemic Syndromes; Monosomy 7; Bone Marrow Clonal Malformations; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndromes; Chronic Myelogenous Leukemia

  16. 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

  17. Skin changes in acute myelogenous leukemia

    OpenAIRE

    Mittal R; Kullar Jastinder; Sethi P; Puneeth

    2000-01-01

    A 65-year old woman developed progressive, firm, mild to moderately itchy, erythematous, papular and nodular lesions, over cheeks, extensors of limbs, scalp and lower back without any accompanying systemic complaints except for severe backache. Initially clinical diagnosis was cutaneous sarcoidosis. However presence of myeloblasts, monoblasts, myelocytes and metamyelocytes in peripheral blood smear and typical histopathology of nodule with mixed cellular infiltrate more around blood vessels, ...

  18. Identification of chromosomal abnormalities relevant to prognosis in chronic lymphocytic leukemia using multiplex ligation-dependent probe amplification.

    NARCIS (Netherlands)

    Stevens-Kroef, M.J.P.L.; Simons, A.; Gorissen, H.; Feuth, A.B.; Weghuis, D.O.; Buijs, A.J.; Raymakers, R.A.P.; Geurts van Kessel, A.H.M.

    2009-01-01

    B-cell chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. Characteristic genomic abnormalities provide clinically important prognostic information. Because karyotyping and fluorescence in situ hybridization (FISH) are laborious techniques, we investigated the d

  19. Characterization of miRNomes in Acute and Chronic Myeloid Leukemia Cell Lines

    Institute of Scientific and Technical Information of China (English)

    Qian Xiong; Jiangwei Yan; Songnian Hu; Xiangdong Fang; Yadong Yang; Hai Wang; Jie Li; Shaobin Wang; Yanming Li; Yaran Yang; Kan Cai; Xiuyan Ruan

    2014-01-01

    Myeloid leukemias are highly diverse diseases and have been shown to be associated with microRNA (miRNA) expression aberrations. The present study involved an in-depth miRNome analysis of two human acute myeloid leukemia (AML) cell lines, HL-60 and THP-1, and one human chronic myeloid leukemia (CML) cell line, K562, via massively parallel signature sequenc-ing. mRNA expression profiles of these cell lines that were established previously in our lab facil-itated an integrative analysis of miRNA and mRNA expression patterns. miRNA expression profiling followed by differential expression analysis and target prediction suggested numerous miRNA signatures in AML and CML cell lines. Some miRNAs may act as either tumor suppres-sors or oncomiRs in AML and CML by targeting key genes in AML and CML pathways. Expres-sion patterns of cell type-specific miRNAs could partially reflect the characteristics of K562, HL-60 and THP-1 cell lines, such as actin filament-based processes, responsiveness to stimulus and phag-ocytic activity. miRNAs may also regulate myeloid differentiation, since they usually suppress dif-ferentiation regulators. Our study provides a resource to further investigate the employment of miRNAs in human leukemia subtyping, leukemogenesis and myeloid development. In addition, the distinctive miRNA signatures may be potential candidates for the clinical diagnosis, prognosis and treatment of myeloid leukemias.

  20. Clinical Research on Treatment of Age-Related Acute Myelogenous Leukemia with Integrated Treatment of Chinese and Western Medicine%中西医结合治疗老年性急性髓细胞白血病临床研究

    Institute of Scientific and Technical Information of China (English)

    胡晓莹; 陈珮; 邱仲川; 赵琳; 黄中迪; 朱小勤

    2015-01-01

    Objective:To observe the clinical curative effect of integrated treatment of Chinese and western medicine on age-related acute myelogenous leukemia ( AML ) . Methods:26 patients with age-related acute myelogenous leukemia were randomly divided into qi-benefiting and heat-clearing formula plus decitabine group(treatment group) and decitabine group(control group). The clinical curative effect and adverse reac tions of the two groups were observed. Result:The completely relieving rate of treatment group was lower than that of the control group and the effective rate was higher than that of the control group. There was no significant difference between the curative effect of the two groups (P>0.05). The significantly effective rate and total effective rate of TCM syndrome improvement of treatment group were significantly higher than that of the control group (P0.05)。治疗组中医证候改善显效率及总有效率明显高于对照组(P<0.05)。治疗过程中治疗组感染发生率、口腔溃疡发生率、恶心呕吐发生率明显低于对照组(P<0.05)。结论:益气清热方联合地西他滨能有效治疗老年性AML,中药能减轻地西他滨的不良反应。

  1. Clofarabine in combination with a standard remission induction regimen (cytosine arabinoside and idarubicin) in patients with previously untreated intermediate and bad-risk acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): phase I results of an ongoing phase I/II study of the leukemia groups of EORTC and GIMEMA (EORTC GIMEMA 06061/AML-14A trial).

    Science.gov (United States)

    Willemze, R; Suciu, S; Muus, P; Halkes, C J M; Meloni, G; Meert, L; Karrasch, M; Rapion, J; Vignetti, M; Amadori, S; de Witte, T; Marie, J P

    2014-06-01

    This study aims to determine the maximum tolerated dose (MTD) of clofarabine combined with the EORTC-GIMEMA 3 + 10 induction regimen (idarubicin + cytosine arabinoside) in adults with untreated acute myelogenous leukemia or high-risk myelodysplastic syndrome. In this phase I trial, 25 patients (median age 56 years) received 5 days of clofarabine as 1-h infusion (arm A) or push injection (arm B) at the dose level of 5 × 10 or 5 × 15 mg/m(2)/day in an algorithmic dose escalation 3 + 3 design. A consolidation course (intermediate dose cytosine arabinoside, idarubicin) was planned for patients in complete remission (CR). Primary endpoint was safety and tolerance as measured by dose limiting toxicity (DLT); secondary endpoints were response rate, other grade III/IV toxicities, and hematological recovery after induction and consolidation. Five DLTs were observed (in arm A: one DLT at 10 mg/m(2)/day, three at 15 mg/m(2)/day; in arm B: one DLT at 15 mg/m(2)/day). Three patients receiving 15 mg/m(2)/day were withdrawn due to adverse events not classified as DLT. Prolonged hypoplasia was observed in five patients. CR + complete remission with incomplete recovery were achieved in 21 patients (11/12 (92 %) receiving clofarabine 10 mg/m(2)/day; 10/13 (77 %) receiving clofarabine 15 mg/m(2)/day). Clofarabine, 5 × 10 mg/m(2)/day, resulted in one DLT and no early treatment withdrawals. MTD of clofarabine combined with cytosine arabinoside and idarubicin is 5 × 10 mg/m(2)/day. PMID:24682421

  2. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation

    DEFF Research Database (Denmark)

    Nicolini, Franck E; Mauro, Michael J; Martinelli, Giovanni;

    2009-01-01

    ), or blastic-phase (BP) and Philadelphia chromosome-positive (Ph)(+) acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation......The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP...

  3. Population Pharmacokinetics of Ofatumumab in Patients With Chronic Lymphocytic Leukemia, Follicular Lymphoma, and Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Struemper, Herbert; Sale, Mark; Patel, Bela R;

    2014-01-01

    Ofatumumab is a human monoclonal antibody directed at CD20 approved for treatment of chronic lymphocytic leukemia. The population pharmacokinetics of intravenous ofatumumab were characterized in patients with relapsed/refractory chronic lymphocytic leukemia, relapsed/refractory follicular lymphoma......, and rheumatoid arthritis, diseases with widely varying CD20(+) B-cell counts in blood. Serum concentration data from a total of 477 patients who received ofatumumab doses ranging from 100 mg to 2000 mg in different dosing regimens were analyzed to determine the pharmacokinetic characteristics of ofatumumab...... across different patient groups and to identify factors contributing to the pharmacokinetic variability. Ofatumumab pharmacokinetics were well described by a linear two-compartment model component to represent non-specific monoclonal antibody clearance from the central compartment interacting...

  4. ChIP-seq Analysis of Human Chronic Myeloid Leukemia Cells.

    Science.gov (United States)

    Anders, Lars; Li, Zhaodong

    2016-01-01

    Many transcription factors, chromatin-associated proteins and regulatory DNA elements are genetically and/or epigenetically altered in cancer, including Chronic Myeloid Leukemia (CML). This leads to deregulation of transcription that is often causally linked to the tumorigenic state. Chromatin-immunoprecipitation coupled with massively parallel DNA sequencing (ChIP-seq) is the key technology to study transcription as it allows in vivo whole-genome mapping of epigenetic modifications and interactions of proteins with DNA or chromatin. However, numerous DNA/chromatin-binding proteins, including EZH2, remain difficult to "ChIP," thus yielding genome-wide binding maps of only suboptimal quality. Here, we describe a ChIP-seq protocol optimized for high-quality protein-genome binding maps that have proven especially useful for studying difficult to 'ChIP' transcription regulatory factors in Chronic Myeloid Leukemia (CML) and related malignancies. PMID:27581144

  5. Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction

    Science.gov (United States)

    2016-08-24

    Adult Mixed Glioma; Adult Pineal Gland Astrocytoma; Adult Solid Neoplasm; AIDS Related Immunoblastic Lymphoma; AIDS-Related Burkitt Lymphoma; AIDS-Related Diffuse Large Cell Lymphoma; AIDS-Related Diffuse Mixed Cell Lymphoma; AIDS-Related Diffuse Small Cleaved Cell Lymphoma; AIDS-Related Hodgkin Lymphoma; AIDS-Related Lymphoblastic Lymphoma; AIDS-Related Lymphoma; AIDS-Related Primary Central Nervous System Lymphoma; Glioma; Lymphoma; Recurrent Adult Brain Neoplasm; Recurrent Adult Soft Tissue Sarcoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Colorectal Carcinoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Melanoma; Recurrent Pancreatic Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Thyroid Gland Carcinoma; Refractory Chronic Lymphocytic Leukemia; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

  6. Chronic myeloid leukemia presenting with absence of basophils and marked dyspoiesis

    Directory of Open Access Journals (Sweden)

    Anand M

    2003-01-01

    Full Text Available A 61-year old woman presented to us with fever, weakness and ecchymotic patches for one year. She had leucocytosis, anemia and thrombocytopenia. Peripheral blood smear showed 62% neutrophils, 32% myelocytes and metamyelocytes, 2% promyelocytes, 1% blasts, 2% monocytes, 1% lymphocytes but no basophils and marked dyspoiesis. Bone marrow picture was essentially the same. A diagnosis of atypical chronic myeloid leukemia was suggested. The correct diagnosis of chronic myeloid leukemia - accelerated phase was, however, made on cytogenetic analysis which showed Philadelphia chromosome (Ph and isochromosome 17q [i(17q]. This case describes a rare and diagnostically difficult presentation of CML arising out of a combination of prominent dyspoiesis and near absence of peripheral blood basophils.

  7. AR-42 in Treating Patients With Advanced or Relapsed Multiple Myeloma, Chronic Lymphocytic Leukemia, or Lymphoma

    Science.gov (United States)

    2016-03-16

    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; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Prolymphocytic 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 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 Multiple Myeloma; 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 Chronic Lymphocytic Leukemia; 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 Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large

  8. Chronic myeloid leukemia presenting with absence of basophils and marked dyspoiesis

    OpenAIRE

    Anand M; Kumar Rajive; Kumar L; Barge S; Singh S

    2003-01-01

    A 61-year old woman presented to us with fever, weakness and ecchymotic patches for one year. She had leucocytosis, anemia and thrombocytopenia. Peripheral blood smear showed 62% neutrophils, 32% myelocytes and metamyelocytes, 2% promyelocytes, 1% blasts, 2% monocytes, 1% lymphocytes but no basophils and marked dyspoiesis. Bone marrow picture was essentially the same. A diagnosis of atypical chronic myeloid leukemia was suggested. The correct diagnosi...

  9. Hodgkin lymphoma transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma

    OpenAIRE

    Krause, John R.; Drinkard, Lee C.; Keglovits, Latoya C.

    2013-01-01

    Transformation to a large cell lymphoma may occur during the course of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in approximately 5% of the cases. This is known as Richter's transformation. A much less frequent transformation to Hodgkin lymphoma may occur. We report a case of CLL/SLL in which a transformation to Hodgkin lymphoma occurred, and we review previously published reports of this transformation. Transformation to Hodgkin lymphoma in CLL/SLL has a poor outcome ...

  10. Isolated extramedullary relapse after allogeneic bone marrow transplantation for chronic myeloid leukemia

    OpenAIRE

    Au, WY; Chan, ACL; Lie, AKW; So, JCC; Liang, R.; Kwong, YL

    1998-01-01

    Relapse of chronic myeloid leukemia (CML) as extramedullary granulocytic sarcoma (GS) after allogeneic bone marrow transplantation (BMT) is a rare occurrence. We report two patients who developed spinal GS as the first indication of relapse after allogeneic BMT for CML. In both cases, the marrow was in morphologic and karyotypic remission. However, fluorescence in situ hybridization (FISH) successfully demonstrated the presence of a minor Ph-positive clone in the marrow, as well as an occult ...

  11. Chronic myeloid leukemia in an adult ghanaian with sporadic neurofibromatosis 1

    Directory of Open Access Journals (Sweden)

    Edeghonghon E Olayemi

    2011-01-01

    Full Text Available Patients with neurofibromatosis type 1 (NF1, a common, progressive, autosomal dominant neurocutaneous disorder, are predisposed to malignancies. Several types of hematologic malignancies have been described in them. However, to date there has been no report to the best of our knowledge of a patient with NF1 developing chronic myeloid leukemia (CML. We present an adult Ghanaian with NF1, who subsequently developed CML. Relevance of the case report is discussed.

  12. Genetic Counseling for DAPK1 Mutation in a Chronic Lymphocytic Leukemia Family

    OpenAIRE

    Lynch, Henry T.; Ferrara, Kelly; Weisenburger, Dennis; Sanger, Warren; Lynch, Jane F.; Thomé, Stephan

    2008-01-01

    Genetic counseling has become the clinical bedrock of hereditary cancer. Countless advances in molecular genetics contributing to the identification of cancer-causing germline mutations have increased its importance. We report perhaps the world’s first genetic counseling experience involving a family with hereditary chronic lymphocytic leukemia and the cancer-causing mutation in the death-associated protein kinase 1 (DAPK1) gene. This hereditary disorder currently lacks any preventive or cura...

  13. 5-Azacytidine in chronic myelomonocytic leukemia: case report and review of literature

    Directory of Open Access Journals (Sweden)

    Mariangela Greco

    2011-03-01

    Full Text Available Hypomethylating drugs are useful in the management of Myelodysplastic syndromes, but  there are only few reports on chronic myelomonocycitic (CMML leukemia patients. We describe our experience in 3 CMML patients treated with azacitidine. Two patients obtained partial response after 4 treatment cycles with only minor toxicity and are in continuous partial response, with stable peripheral blood counts, at 29 and 30 cycles from treatment start.

  14. 5-Azacytidine in chronic myelomonocytic leukemia: case report and review of literature

    OpenAIRE

    Marianna Criscuolo; Mariangela Greco; Luana Fianchi; Livio Pagano; Maria Teresa Voso

    2011-01-01

    Hypomethylating drugs are useful in the management of Myelodysplastic syndromes, but  there are only few reports on chronic myelomonocycitic (CMML) leukemia patients. We describe our experience in 3 CMML patients treated with azacitidine. Two patients obtained partial response afte...

  15. 5-Azacytidine in Chronic Myelomonocytic Leukemia: Case Report and Review of Literature.

    Science.gov (United States)

    Greco, M.; Criscuolo, M.; Fianchi, L.; Fabiani, E.; Pagano, L.; Voso, MT.

    2011-01-01

    Hypomethylating drugs are useful in the management of Myelodysplastic syndromes, but there are only few reports on chronic myelomonocycitic (CMML) leukemia patients. We describe our experience in 3 CMML patients treated with azacitidine. Two patients obtained partial response after 4 treatment cycles with only minor toxicity and are in continuous partial response, with stable peripheral blood counts, at 29 and 30 cycles from treatment start. PMID:21625315

  16. 5-Azacytidine in Chronic Myelomonocytic Leukemia: Case Report and Review of Literature.

    OpenAIRE

    Greco, M; Criscuolo, M.; Fianchi, L.; Fabiani, E.; Pagano, L; Voso, MT.

    2011-01-01

    Hypomethylating drugs are useful in the management of Myelodysplastic syndromes, but there are only few reports on chronic myelomonocycitic (CMML) leukemia patients. We describe our experience in 3 CMML patients treated with azacitidine. Two patients obtained partial response after 4 treatment cycles with only minor toxicity and are in continuous partial response, with stable peripheral blood counts, at 29 and 30 cycles from treatment start.

  17. Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism

    OpenAIRE

    Raimondo, Stefania; Saieva, Laura; Corrado, Chiara; Fontana, Simona; Flugy, Anna; Rizzo, Aroldo; De Leo, Giacomo; Alessandro, Riccardo

    2015-01-01

    Background Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder in which leukemic cells display a reciprocal t(9:22) chromosomal translocation that results in the formation of the chimeric BCR-ABL oncoprotein, with a constitutive tyrosine kinase activity. Consequently, BCR-ABL causes increased proliferation, inhibition of apoptosis, and altered adhesion of leukemic blasts to the bone marrow (BM) microenvironment. It has been well documented that cancer cells can generat...

  18. Chronic lymphocytic leukemia/small lymphocytic lymphoma presenting as septic arthritis of the shoulder

    Energy Technology Data Exchange (ETDEWEB)

    Donovan, Andrea; Schweitzer, Mark E.; Nomikos, George [NYU Hospital for Joint Diseases, New York, NY (United States); Garcia, Roberto A. [Bellevue Hospital Center, New York, NY (United States)

    2008-11-15

    We report a case of a 53-year-old man presenting with shoulder pain mimicking septic arthritis. Laboratory findings were atypical. Biopsy performed to assess for possible osteomyelitis demonstrated chronic lymphocytic leukemia/small lymphocytic lymphoma. Intra-articular lymphoma is a rare but important consideration in patients with atypical clinical presentation. Imaging alone may be insufficient to render diagnosis as lymphoma can mimic infection, synovial hypertrophic processes, and depositional arthropathy. (orig.)

  19. Heightened BTK-dependent cell proliferation in unmutated chronic lymphocytic leukemia confers increased sensitivity to ibrutinib

    OpenAIRE

    Guo, Ailin; Lu, Pin; Galanina, Natalie; Nabhan, Chadi; Smith, Sonali M.; Coleman, Morton; Wang, Y. Lynn

    2015-01-01

    In chronic lymphocytic leukemia (CLL), patients with unmutated immunoglobulin heavy chain variable region gene (UM-CLL) have worse outcomes than mutated CLL (M-CLL) following chemotherapy or chemoimmunotherapy. However, in the era of BCR-targeted therapies, the adverse prognostic impact of unmutated IGHV seems to be diminishing, and there are clinical datasets showing unexpected improved responses in UM-CLL. We investigated the biological differences of BTK activity between these subgroups an...

  20. A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia

    OpenAIRE

    Tucker DL; Rule SA

    2015-01-01

    David L Tucker, Simon A Rule Department of Haematology, Plymouth Hospitals NHS Trust, Plymouth, UK Abstract: Although chemo-immunotherapy remains at the forefront of first-line treatment for mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), small molecules, such as ibrutinib, are beginning to play a significant role, particularly in patients with multiply relapsed or chemotherapy-refractory disease and where toxicity is an overriding concern. Ibrutinib is a first-in-class, ...

  1. The clinical significance of 8q24/MYC rearrangement in chronic lymphocytic leukemia.

    Science.gov (United States)

    Li, Yan; Hu, Shimin; Wang, Sa A; Li, Shaoying; Huh, Yang O; Tang, Zhenya; Medeiros, L Jeffrey; Tang, Guilin

    2016-05-01

    Chromosome 8q24/MYC rearrangement is associated with Burkitt lymphoma and some aggressive B-cell lymphomas, but is rare in chronic lymphocytic leukemia. We here report a cohort of 20 chronic lymphocytic leukemia patients with 8q24/MYC rearrangement, 3 detected at time of initial diagnosis and 17 acquired after a median interval of 48 months. At the time when 8q24/MYC arrangement was detected, 18 patients had B-symptoms, 17 had lymphadenopathy, and 17 had splenomegaly. Histologically, typical chronic lymphocytic leukemia morphology was seen in six patients, increased prolymphocytes in nine and Richter's transformation in five patients. Eighteen patients had karyotypic information available that showed t(8;v) in a complex karyotype in 12 patients and in a non-complex karyotype in 6 patients. Fluorescence in situ hybridization confirmed MYC rearrangement in 17/17 patients. All patients required therapy after 8q24/MYC rearrangement was detected. At last follow-up, five of six patients with a non-complex karyotype were alive after a median of 74 months (10~143 months) from the detection of 8q24/MYC rearrangement. In contrast, 10 of 12 patients with a complex karyotype died with a median survival of 5.5 months. We conclude that 8q24/MYC rearrangement in chronic lymphocytic leukemia is rare and often acquired during the course of disease. If it is presented in a complex karyotype, it is often associated with Richter's transformation, refractory to therapy and an aggressive clinical course; on the other hand, if it is present in a non-complex karyotype, patients often respond to risk-adapted therapies and achieve remission. PMID:26916070

  2. No evidence of transmission of chronic lymphocytic leukemia through blood transfusion

    DEFF Research Database (Denmark)

    Hjalgrim, Henrik; Rostgaard, Klaus; Vasan, Senthil K;

    2015-01-01

    Monoclonal B-cell lymphocytosis (MBL) is a precursor of chronic lymphocytic leukemia (CLL). Observations of MBL in blood donors raise concern that transmitted MBL may cause recipient CLL. Using a database with health information on 1.5 million donors and 2.1 million recipients, we compared CLL oc...... transfusion experience over more than 30 years indicate that MBL/CLL transmission does not contribute importantly to recipient CLL risk....

  3. Induced Resistance to Ofatumumab Mediated Cell Clearance Mechanisms, Including Complement Dependent Cytotoxicity, in Chronic Lymphocytic Leukemia

    OpenAIRE

    Baig, Nisar A.; Taylor, Ronald P.; Lindorfer, Margaret A.; Church, Amy K.; LaPlant, Betsy R.; Pettinger, Adam M.; Shanafelt, Tait D.; Nowakowski, Grzegorz S.; Zent, Clive S.

    2014-01-01

    Ofatumumab (OFA), a human CD20 targeting mAb, kills B-lymphocytes utilizing the innate immune system including complement dependent cytotoxicity (CDC). The efficacy of OFA in patients with chronic lymphocytic leukemia (CLL) is limited by drug resistance, which is not well characterized. To better understand mechanisms of resistance, we prospectively studied CLL cells isolated from blood samples collected before and after in vivo exposure to the initial dose of OFA therapy in 25 patients under...

  4. Imatinib resistance: a review of alternative inhibitors in chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Roberta Bitencourt

    2011-12-01

    Full Text Available The development of point mutations in the BCR-ABL kinase domain is the main reason for imatinib resistance in chronic myeloid leukemia. Different detection methods are used in chronic myeloid leukemia monitoring, such as direct sequencing, denaturing high performance liquid chromatography and allele specific polymerase chain reaction. Mutation analysis has become mandatory during patient workup of chronic myeloid leukemia in order for the physician to choose the most suitable tyrosine kinase inhibitor. This article, a review of possible therapies used to overcome imatinib resistance, investigates the current position by searching the PubMed electronic database using the following keywords: imatinib, dasatinib, nilotinib, aurora kinase, SRC kinase, mutation, treatment, drugs and resistance. New tyrosine kinase inhibitors include BCR-ABL kinase selective inhibitors, dual ABL/SRC kinase inhibitors and aurora kinase inhibitors. Awareness of the spectrum of new drugs against mutations, in particular the T315I mutation, makes it possible to properly select the best therapy for each patient.

  5. Chronic Myeloid Leukemia with Variant Chromosomal Translocations: Results of Treatment with Imatinib Mesylate

    Directory of Open Access Journals (Sweden)

    Rohan Bhise

    2013-01-01

    Full Text Available Objective: To evaluate the efficacy of imatinib in chronic myeloid leukemia patients with variant translocations. Methods: Forty eight chronic myeloid leukemia patients carrying variant translocations and treated with imatinib at our institute were considered for the study. Survival and response rates were evaluated. Results: The median follow up was 48 months(m. Forty three (89.58% patients achieved complete hematologic response. Thirty one (64.58% patients achieved complete cytogenetic response and 19(39.58% achieved major molecular response anytime during their follow up period. Only 18.75% of the patients achieved complete cytogenetic response and major molecular response within the stipulated time frames.The estimated overall survival at 48 m median follow up was 81.2%.The progression free survival was also 81.2% and the event free survival was 79.1%.There was no significant survival difference between low vs intermediate and high risk sokal group. Conclusion: We report suboptimal responses to imatinib in chronic myeloid leukemia with variant translocations. Further studies with imatinib and the newer more active drugs dasatinib and nilotinib are justified.

  6. Quantification of newly produced B and T lymphocytes in untreated chronic lymphocytic leukemia patients

    Directory of Open Access Journals (Sweden)

    Caimi Luigi

    2010-11-01

    Full Text Available Abstract Background The immune defects occurring in chronic lymphocytic leukemia are responsible for the frequent occurrence of infections and autoimmune phenomena, and may be involved in the initiation and maintenance of the malignant clone. Here, we evaluated the quantitative defects of newly produced B and T lymphocytes. Methods The output of B and T lymphocytes from the production and maturation sites was analyzed in chronic lymphocytic leukemia patients and healthy controls by quantifying kappa-deleting recombination excision circles (KRECs and T-cell receptor excision circles (TRECs by a Real-Time PCR assay that simultaneously detects both targets. T-lymphocyte subsets were analyzed by six-color flow cytometric analysis. Data comparison was performed by two-sided Mann-Whitney test. Results KRECs level was reduced in untreated chronic lymphocytic leukemia patients studied at the very early stage of the disease, whereas the release of TRECs+ cells was preserved. Furthermore, the observed increase of CD4+ lymphocytes could be ascribed to the accumulation of CD4+ cells with effector memory phenotype. Conclusions The decreased number of newly produced B lymphocytes in these patients is likely related to a homeostatic mechanism by which the immune system balances the abnormal B-cell expansion. This feature may precede the profound defect of humoral immunity characterizing the later stages of the disease.

  7. Economic evaluation of dasatinib in the treatment of chronic myeloid leukemia patients resistant to imatinib in Chile

    OpenAIRE

    Milva Caputo; Eleonora Aiello; Juan Esteban Valencia; John Jairo Orozco Giraldo

    2011-01-01

    Objective. Within the framework of Chronic Myelogenous Leukaemia (CML) treatment in Chile, and based on a previously performed economic evaluation, we compared the costs and cost-effectiveness ratio of using 100 mg/day and 140 mg/day doses of dasatinib with the use of 800 mg/day doses of nilotinib or an increased dose of imatinib (800mg/day), for each phase of the disease, in patients who developed resistance or intolerance to habitual doses of imatinib. Methods. A Markov model was used for t...

  8. Janus kinase 2 regulates Bcr–Abl signaling in chronic myeloid leukemia

    OpenAIRE

    Samanta, A.; Perazzona, B; Chakraborty, S.; Sun, X.; Modi, H; Bhatia, R.; Priebe, W.; Arlinghaus, R.

    2010-01-01

    Despite the success of imatinib mesylate (IM) in the early chronic phase of chronic myeloid leukemia (CML), patients are resistant to IM and other kinase inhibitors in the later stages of CML. Our findings indicate that inhibition of Janus kinase 2 (Jak2) in Bcr–Abl+ cells overcomes IM resistance although the precise mechanism of Jak2 action is unknown. Knocking down Jak2 in Bcr–Abl+ cells reduced levels of the Bcr–Abl protein and also the phosphorylation of Tyr177 of Bcr–Abl, and Jak2 overex...

  9. Chronic myeloid leukemia with hyperdiploidy: A case report with review of literature

    Directory of Open Access Journals (Sweden)

    Sushma Belurkar

    2013-01-01

    Full Text Available Chronic myeloid leukemia (CML is a common marrow stem cell neoplasm characterized by the presence of the Philadelphia (Ph chromosome in more than 90% of patients. Studies have shown that CML can be associated with various other cytogenetic abnormalities. 5-10% of these cases can show complex translocations involving other chromosomes in addition to Ph chromosome. Here, we report a Ph-positive CML patient with a hyperdiploid karyotype who presented clinically in chronic phase but progressed to blast crisis in spite of treatment with Imatinib. This case highlights the significance of cytogenetic abnormalities on the prognosis in CML.

  10. Post-transplant outcome in chronic myeloid leukemia

    International Nuclear Information System (INIS)

    To determine post-transplant survival in chronic myeloid leukaemia patients undergoing allogeneic stem cell transplant. All patients of chronic myeloid leukaemia in chronic phase having HLA identical donor and age under 55 years, normal hepatic, renal and cardiac functions with good performance status were selected. Patients in accelerated phase or blast crisis, poor performance status, impaired hepatic, renal, cardiac functions or pregnancy were excluded. Survival was calculated from the date of transplant to death or last follow-up according to Kaplan-Meier and Cox (proportional hazard) regression analysis methods. Thirty seven patients with chronic myeloid leukaemia underwent allogeneic stem cell transplant from HLA identical sibling donors. Thirty two patients were male and five were females. Median age of patients was 28 years. All patients and donors were CMV positive. Post-transplant complications encountered were acute GvHD (Grade II-IV) (n=13, 35.1%), chronic GvHD in 18.9% (n=7), Veno Occlusive Disease (VOD) in 5.4% (n=2), acute renal failure in 2.7% (n=1), haemorrhagic cystitis in 2.7% (n=1), bacterial infections in 40.5% (n=15), fungal infections in 16.2% (n=6), CMV infection in 5.4% (n=2), tuberculosis in 5.4% (n=2), Herpes Zoster infection 2.7% (n=1) and relapse in 2.7% (n=1). Mortality was observed in 27% (n=10). Major causes of mortality were GvHD, VOD, septicemia, CMV infection and disseminated Aspergillosis. Overall Disease Free Survival (DFS) was 73% with a median duration of follow-up of 47.4 + 12 months. DFS was 81% in standard risk and 54.5% in high-risk group. Results of allogeneic stem cell transplant in standard risk group CML patients were good and comparable with other international centres, however, results in high-risk CML patients need further improvement, although, number of patients in this group is small. (author)

  11. Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

    Science.gov (United States)

    2016-06-17

    B-Cell Prolymphocytic Leukemia; Plasma Cell Leukemia; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Non-Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

  12. Nilotinib 300 mg twice daily: an academic single-arm study of newly diagnosed chronic phase chronic myeloid leukemia patients

    Science.gov (United States)

    Castagnetti, Fausto; Breccia, Massimo; Gugliotta, Gabriele; Martino, Bruno; D’Adda, Mariella; Stagno, Fabio; Carella, Angelo Michele; Avanzini, Paolo; Tiribelli, Mario; Trabacchi, Elena; Visani, Giuseppe; Gobbi, Marco; Salvucci, Marzia; Levato, Luciano; Binotto, Gianni; Capalbo, Silvana Franca; Bochicchio, Maria Teresa; Soverini, Simona; Cavo, Michele; Martinelli, Giovanni; Alimena, Giuliana; Pane, Fabrizio; Saglio, Giuseppe; Rosti, Gianantonio; Baccarani, Michele

    2016-01-01

    The introduction and the extended clinical use of nilotinib in the first-line treatment of chronic myeloid leukemia have been based on company-sponsored trials. Independent confirmations are extremely important. We report an investigator-sponsored study of nilotinib 300 mg twice daily in 130 chronic myeloid leukemia patients in early chronic phase. A deep molecular response was achieved in 46% (MR4.0) and 17% (MR4.5) of patients at 2 years; 58% of the enrolled patients achieved a MR4.0 at least once, with a sustained MR4.0 in 52% of them. With a median observation of 29 months (range 24–37 months), 77% of patients were still on treatment with nilotinib. The reasons for permanent discontinuation were: 3% progression, 5% failure or suboptimal response, 8% adverse events, 1% treatment-free remission, and 5% other reasons. Thirteen thrombotic arterial events were reported in 12 patients. A prospective evaluation of metabolic effects showed an increase of fasting glucose without significant variations of glycated hemoglobin, an increase of total cholesterol (both low density lipoprotein and high density lipoprotein fractions) and a decrease of triglycerides. This study confirms a high and rapid efficacy of nilotinib 300 mg twice daily and provides detailed information on the type and incidence of non-hematologic and metabolic adverse events (clinicaltrials.gov identifier: 01535391). PMID:27470600

  13. High-vs low-dose cytarabine combined with interferon alfa in patients with first chronic phase chronic myeloid leukemia. A prospective randomized phase III study

    NARCIS (Netherlands)

    Deenik, W.; van der Holt, B.; Verhoef, G. E. G.; Schattenberg, A. V. M. B.; Verdonck, L. F.; Daenen, S. M. G. J.; Zachee, P.; Westveer, P. H. M.; Smit, W. M.; Wittebol, S.; Schouten, H. C.; Lowenberg, B.; Ossenkoppele, G. J.; Cornelissen, J. J.

    2007-01-01

    A prospective randomized phase III study was performed to evaluate whether intensified cytarabine would induce a higher response rate and longer event-free interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML). One hundred and eighteen patients with CML in early chronic phase

  14. High-vs low-dose cytarabine combined with interferon alfa in patients with first chronic phase chronic myeloid leukemia : A prospective randomized phase III study

    NARCIS (Netherlands)

    Deenik, W.; Holt, B. van der; Verhoef, G.E.; Schattenberg, A.V.M.B.; Verdonck, L.F.; Daenen, S.M.G.J.; Zachee, P.; Westveer, P.H.; Smit, W.M.; Wittebol, S.; Schouten, H.C.; Lowenberg, B.; Ossenkoppele, G.J.; Cornelissen, J.J.L.M.

    2007-01-01

    A prospective randomized phase III study was performed to evaluate whether intensified cytarabine would induce a higher response rate and longer event-free interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML). One hundred and eighteen patients with CML in early chronic phase

  15. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia : 2-year follow-up from a randomized phase 3 trial (DASISION)

    NARCIS (Netherlands)

    Kantarjian, Hagop M.; Shah, Neil P.; Cortes, Jorge E.; Baccarani, Michele; Agarwal, Mohan B.; Soledad Undurraga, Maria; Wang, Jianxiang; Kassack Ipina, Juan Julio; Kim, Dong-Wook; Ogura, Michinori; Pavlovsky, Carolina; Junghanss, Christian; Milone, Jorge H.; Nicolini, Franck E.; Robak, Tadeusz; Van Droogenbroeck, Jan; Vellenga, Edo; Bradley-Garelik, M. Brigid; Zhu, Chao; Hochhaus, Andreas

    2012-01-01

    Dasatinib is a highly potent BCR-ABL inhibitor with established efficacy and safety in imatinib-resistant/-intolerant patients with chronic myeloid leukemia (CML). In the phase 3 DASISION trial, patients with newly diagnosed chronic-phase (CP) CML were randomized to receive dasatinib 100 mg (n = 259

  16. Complementary and alternative medicine use in patients with chronic lymphocytic leukemia: an Italian multicentric survey.

    Science.gov (United States)

    D'Arena, Giovanni; Laurenti, Luca; Coscia, Marta; Cortelezzi, Agostino; Chiarenza, Annalisa; Pozzato, Gabriele; Vigliotti, Maria Luigia; Nunziata, Giuseppe; Fragasso, Alberto; Villa, Maria Rosaria; Grossi, Alberto; Selleri, Carmine; Deaglio, Silvia; La Sala, Antonio; Del Poeta, Giovanni; Simeon, Vittorio; Aliberti, Luig; De Martino, Laura; Giudice, Aldo; Musto, Pellegrino; De Feo, Vincenzo

    2014-04-01

    Complementary and alternative medicine (CAM) is common in patients with cancer and its use is steadily increasing over time. We performed a multicenter survey in which the use of CAM in 442 Italian patients with chronic lymphocytic leukemia (CLL), the commonest form of leukemia in Western countries, was assessed. Data were collected by means of a face-to-face standardized questionnaire with several items. Mean age was 69 years; 258 patients (58%) were male and 184 (42%) female. Seventy-three patients (16.5%) were found to be CAM users. The most common CAM therapies were green tea, aloe formulations and high dose vitamins. Predictors of CAM use were female gender, younger age, higher education level, internet availability and newspaper reading. The reasons for CAM popularity among these patients are complex. Given the number of patients combining therapy with CAM and its possible drug interactions, doctor interest as well as patient education about CAM should be improved. PMID:23829282

  17. Progress in BCL2 inhibition for patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Tam, Constantine S; Seymour, John F; Roberts, Andrew W

    2016-04-01

    The prosurvival protein BCL2 is uniformly expressed in chronic lymphocytic leukemia (CLL), and enables leukemia cell survival in the face of cytotoxic treatment and increasing genomic, metabolic, and oxidative stresses. The therapeutic potential of BCL2 inhibition was first observed in the clinic following BCL2 antisense therapy. Subsequently, a number of small molecule inhibitors were developed to mimic the function of the pro-apoptotic BH3-only proteins (BH3-mimetics). These molecules are now in late-phase clinical trials and demonstrate potent activity, including the occurrence of acute tumor lysis syndrome in subjects with multiply relapsed, chemorefractory CLL. In this review, we discuss the history and summarize current knowledge regarding BCL2 inhibition as therapy of CLL. PMID:27040706

  18. Complementary and alternative medicine use in patients with chronic lymphocytic leukemia: an Italian multicentric survey.

    Science.gov (United States)

    D'Arena, Giovanni; Laurenti, Luca; Coscia, Marta; Cortelezzi, Agostino; Chiarenza, Annalisa; Pozzato, Gabriele; Vigliotti, Maria Luigia; Nunziata, Giuseppe; Fragasso, Alberto; Villa, Maria Rosaria; Grossi, Alberto; Selleri, Carmine; Deaglio, Silvia; La Sala, Antonio; Del Poeta, Giovanni; Simeon, Vittorio; Aliberti, Luig; De Martino, Laura; Giudice, Aldo; Musto, Pellegrino; De Feo, Vincenzo

    2014-04-01

    Complementary and alternative medicine (CAM) is common in patients with cancer and its use is steadily increasing over time. We performed a multicenter survey in which the use of CAM in 442 Italian patients with chronic lymphocytic leukemia (CLL), the commonest form of leukemia in Western countries, was assessed. Data were collected by means of a face-to-face standardized questionnaire with several items. Mean age was 69 years; 258 patients (58%) were male and 184 (42%) female. Seventy-three patients (16.5%) were found to be CAM users. The most common CAM therapies were green tea, aloe formulations and high dose vitamins. Predictors of CAM use were female gender, younger age, higher education level, internet availability and newspaper reading. The reasons for CAM popularity among these patients are complex. Given the number of patients combining therapy with CAM and its possible drug interactions, doctor interest as well as patient education about CAM should be improved.

  19. A different approach to telomere analysis with ddPRINS in chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Palanduz, Sukru; Serakinci, Nedime; Cefle, Kivanc;

    2006-01-01

    in acute leukemias where the cell turnover is high. B-cell chronic lymphocytic leukemia (CLL) is a particularly interesting haematological malignancy in regard to telomere dynamics because most of the malignant cells in CLL are mitotically inactive. In this study, we analysed the telomere length......Telomeric sequences, located at the very end of the chromosomes, compensate for the chromosomal shortening as it happens after each round of cell division. Telomeric sequences influence the progress of cellular senescence and cancer progression. It has been reported that telomeres are shortened...... in patients with B-cell CLL in a comparison with the control group by using ddPRINS technique. Twenty patients with CLL and four healthy donors as a control group were included. We found short telomeres and no detectable telomeric repeats at the sites of chromosome fusion. We hypothesise that the telomeric...

  20. AUTOIMMUNE CYTOPENIAS IN CHRONIC LYMPHOCYTIC LEUKEMIA, FACTS AND MYTHS

    Directory of Open Access Journals (Sweden)

    Pavankumar Tandra

    2013-11-01

    Full Text Available CLL has been defined as presence of more than 5000 small mature appearing monoclonal B lymphocytes with a specific immunophenotype in peripheral blood. It is a well-known fact that CLL is associated with autoimmune cytopenias. CLL cells are CD5+ B lymphocytes, and usually are not the “guilty” cells which produce autoantibodies. T cell defect is another characteristic of CLL and the total number of T cells is increased, and there is inversion of the CD4/CD8 ratio. Autoimmune hemolytic anemia (AIHA is the most common autoimmune complication of CLL and has been reported in 10-25% of CLL patients. However, the stage-adjusted estimated rate of AIHA in CLL is about 5%. Conversely, CLL is three times more common in patients who present with AIHA. Direct agglutinin test (DAT is positive in 7-14% of CLL patients but AIHA may also occur in DAT negative patients. Autoimmune thrombocytopenia (AIT is the second most common complication of CLL and has been reported in 2-3% of patients. DAT is positive in AIT but presence of antiplatelet antibodies is neither diagnostic nor reliable. Autoimmune neutropenia (AIN and pure red cell aplasia (PRCA are very rare complications of CLL and like other autoimmune complications of CLL may occur at any clinical stage. It is believed that most case reports of AIN and PRCA in CLL actually belong to large granular lymphocytic leukemia (LGL. Non-hematologic autoimmune complications of CLL including cold agglutinin disease (CAD, paraneoplastic pemphigus (PNP, acquired angioedema, and anti-myelin associated globulin are rare. Before starting any treatment, clinicians should distinguish between autoimmune cytopenias and massive bone marrow infiltration since autoimmune complications of CLL are not necessarily equal to advanced disease with poor prognosis. According to IWCLL guideline, steroids are the mainstay of treatment of simple autoimmunity. Intravenous immunoglobulin (IVIg, cyclosporine, and rituximab are used in

  1. Ionizing radiation and risk of chronic lymphocytic leukemia in the 15-country study of nuclear industry workers

    DEFF Research Database (Denmark)

    Vrijheid, Martine; Cardis, Elisabeth; Ashmore, Patrick;

    2008-01-01

    In contrast to other types of leukemia, chronic lymphocytic leukemia (CLL) has long been regarded as non-radiogenic, i.e. not caused by ionizing radiation. However, the justification for this view has been challenged. We therefore report on the relationship between CLL mortality and external ioni......; an extended follow-up of the cohorts is merited and would ideally include incident cancer cases....

  2. Three newly approved drugs for chronic lymphocytic leukemia (CLL): Incorporating ibrutinib, idelalisib and obinutuzumab into clinical practice

    OpenAIRE

    Sanford, David; Wierda, William G.; Burger, Jan A.; Keating, Michael J.; O’Brien, Susan M.

    2015-01-01

    Three agents have received FDA approval for treatment of chronic lymphocytic leukemia (CLL) within the last year. Ibrutinib and idelalisib block B-cell receptor signaling through inhibition of BTK and PI3Kδ molecules respectively, interfering with several pathways required for leukemia cell survival. Idelalisib has shown efficacy in in the relapsed setting and is currently approved for use in combination with rituximab. Ibrutinib has been studied in patients with relapsed CLL and as frontline...

  3. Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematological Cancer Who Are Undergoing Umbilical Cord Blood Transplant

    Science.gov (United States)

    2016-10-21

    Acute Biphenotypic Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Myelodysplastic Syndrome; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Myelodysplastic Syndrome; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; RAEB-2; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive

  4. Chronic hepatitis E virus infection in a patient with leukemia and elevated transaminases: a case report

    Directory of Open Access Journals (Sweden)

    Gauss Annika

    2012-10-01

    Full Text Available Abstract Introduction Acute hepatitis E virus infection may cause mild, self-limiting hepatitis, either as epidemic outbreaks or sporadic cases, the latter of which have been reported in industrialized countries. Chronic infections are uncommon and have been reported in immunosuppressed patients, patients with human immunodeficiency virus infection, and patients with hematological malignancies. Case presentation A 46-year-old Caucasian man was admitted to the gastroenterology clinic with a history of increasing transaminases, persistent exhaustion, and occasional right-side abdominal pain over the course of a 6-month period. B-cell chronic lymphocytic leukemia had been diagnosed several years earlier, and the patient was treated with rituximab, pentostatin, and cyclophosphamide. A diagnostic workup ruled out autoimmune and metabolic liver disease, hepatitis A-C, and herpes virus infection. A physical examination revealed enlarged axillary lymph nodes. The results of an abdominal ultrasound examination were otherwise unremarkable. Hepatitis E virus infection was diagnosed by detection of hepatitis E virus-specific antibodies. Blood samples were positive for hepatitis E virus ribonucleic acid with high viral loads for at least 8 months, demonstrating a rare chronic hepatitis E virus infection. Sequencing and phylogenetic analysis revealed hepatitis E virus genotype 3c with homologies to other European isolates from humans and swine, indicating an autochthonous infection. Conclusions Usually, hepatitis E virus infection appears as an acute infection; rare chronic infections have been reported for transplant patients, patients with human immunodeficiency virus, and patients with hematological malignancies. The chronic nature of hepatitis E infection in our patient was most likely induced by the immunosuppressive B-cell chronic lymphocytic leukemia treatment. The differential diagnosis in patients with unexplained hepatitis should include hepatitis E

  5. Adult Leukemias

    OpenAIRE

    Moore, Lyall K.

    1984-01-01

    Over the past several years, advances have been made in the classification, diagnosis and therapy of the adult leukemias. The overall prognosis and quality of life have improved greatly, especially for patients with acute nonlymphoblastic leukemias. Some of the advances are described in this article. The importance of the clinical, laboratory and diagnostic tests for acute, chronic granulocytic and chronic lymphocytic leukemia are stressed. The therapy and prognosis for patients with the vari...

  6. Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Keller-von Amsberg G

    2013-03-01

    Full Text Available Gunhild Keller-von Amsberg,1 Steffen Koschmieder21Department of Hematology and Oncology, University Cancer Center Hamburg, University Hospital Hamburg Eppendorf, 2Department of Medicine (Hematology, Oncology, and Stem Cell Transplantation, University Medical Center of Aachen and RWTH Aachen University, Aachen, GermanyAbstract: Bosutinib (SKI-606 is an orally available, once-daily, dual Src and Abl kinase inhibitor with promising clinical potential in first-, second-, and third-line treatment of chronic myeloid leukemia (CML. Bosutinib effectively inhibits wild-type BCR-ABL and most imatinib-resistant BCR-ABL mutations except for V299L and T315I. Low hematologic toxicity is a remarkable characteristic of this novel second-generation tyrosine kinase inhibitor, and this has been ascribed to its minimal activity against the platelet-derived growth factor receptor and KIT. Low-grade, typically self-limiting diarrhea, which usually appears within the first few weeks after treatment initiation, represents the predominant toxicity of bosutinib. Other treatment-associated adverse events are mostly mild to moderate. Bosutinib has been approved by the US Food and Drug Administration for the treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive CML in adult patients with resistance or intolerance to prior therapy. This review summarizes the main properties of bosutinib and the currently available data on its clinical potential in the treatment of CML.Keywords: bosutinib, chronic myeloid leukemia, BCR-ABL, Src/Abl kinase inhibitor, point mutation, imatinib resistance

  7. Platelet Dysfunction in Patients with Chronic Myeloid Leukemia: Does Imatinib Mesylate Improve It?

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    Olga Meltem Akay

    2016-05-01

    Full Text Available Objective: The aim of this study was to investigate the effects of imatinib mesylate on platelet aggregation and adenosine triphosphate (ATP release in chronic myeloid leukemia patients. Materials and Methods: Platelet aggregation and ATP release induced by 5.0 mM adenosine diphosphate, 0.5 mM arachidonic acid, 1.0 mg/ mL ristocetin, and 2 µg/mL collagen were studied by whole blood platelet lumi-aggregometer in 20 newly diagnosed chronic myeloid leukemia patients before and after imatinib mesylate treatment. Results: At the time of diagnosis, 17/20 patients had abnormal platelet aggregation results; 8 (40% had hypoactivity, 6 (30% had hyperactivity, and 3 (15% had mixed hypo- and hyperactivity. Repeat platelet aggregation studies were performed after a mean of 19 months (min: 5 months-max: 35 months in all patients who received imatinib mesylate during this period. After therapy, 18/20 (90% patients had abnormal laboratory results; 12 (60% had hypoactive platelets, 4 (20% had mixed hypo- and hyperactive platelets, and 2 (10% had hyperactive platelets. Three of the 8 patients with initial hypoactivity remained hypoactive, while 2 developed a mixed picture, 2 became hyperactive, and 1 normalized. Of the 6 patients with initial hyperactivity, 4 became hypoactive and 2 developed a mixed pattern. All of the 3 patients with initial hypo- and hyperactivity became hypoactive. Finally, 2 of the 3 patients with initial normal platelets became hypoactive while 1 remained normal. There was a significant decrease in ristocetin-induced platelet aggregation after therapy (p0.05. Conclusion: These findings indicate that a significant proportion of chronic myeloid leukemia patients have different patterns of platelet function abnormalities and imatinib mesylate has no effect on these abnormalities, with a significant impairment in ristocetin-induced platelet aggregation.

  8. Clinical utility and patient considerations in the use of ofatumumab in chronic lymphocytic leukemia

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    Frustaci AM

    2015-09-01

    Full Text Available Anna Maria Frustaci, Alessandra Tedeschi, Paola Picardi, Roberto Cairoli, Marco MontilloDepartment of Hematology, Niguarda Cancer Center, Niguarda Ca' Granda Hospital, Milan, Italy Abstract: Treatment aim for chronic lymphocytic leukemia has been radically changed over the past years from providing only a palliative approach to reaching disease eradication and improving survival. Ofatumumab is a monoclonal humanized antibody with peculiar in vitro and in vivo properties, at present approved for double fludarabine and alemtuzumab refractory chronic lymphocytic leukemia. Its efficacy in this subset of patients, who typically have an unfavorable prognosis, facilitated its use in different Phase II and III trials. Ofatumumab as single agent or combined with chemotherapeutic or biologic agents, led to sundry results in the setting of both previously treated or untreated patients. Its role in maintenance therapy is also under investigation. Further advances concerning ofatumumab administration as first line therapy in combination with chlorambucil, came recently from the COMPLEMENT 1 study. Results from this trial will open the door to new perspectives of its use in treatment-naïve patients. Ofatumumab was well tolerated in almost all the studies, with the main adverse events relating mostly to infusion reaction. Hematologic toxicity, especially neutropenia, was also common. A significant improvement in patients' quality of life was reported following ofatumumab treatment and this was mainly due to its effect on constitutional symptoms. Nevertheless, some concerns remain regarding the long-term efficacy of the drug in terms of response duration and survival. The real strength of this drug needs to be confirmed by further studies and direct comparative trials. Keywords: ofatumumab, chronic lymphocytic leukemia, refractory, alemtuzumab, fludarabine, high risk

  9. Chaetoglobosin A preferentially induces apoptosis in chronic lymphocytic leukemia cells by targeting the cytoskeleton

    DEFF Research Database (Denmark)

    Knudsen, Peter Boldsen; Hanna, B.; Ohl, S.;

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is an incurable malignancy of mature B cells. One of the major challenges in treatment of CLL is the achievement of a complete remission to prevent relapse of disease originating from cells within lymphoid tissues and subsequent chemoresistance. In search...... for novel drugs that target CLL cells also in protective microenvironments, we performed a fungal extract screen using cocultures of primary CLL cells with bone marrow-derived stromal cells. A metabolite produced by Penicillium aquamarinium was identified as Chaetoglobosin A, a member of the cytochalasan...

  10. Improving the treatment outcome of patients with chronic lymphocytic leukemia through targeted antibody therapy.

    Science.gov (United States)

    Stephens, Deborah M; Byrd, John C

    2013-04-01

    Therapy for chronic lymphocytic leukemia (CLL) has evolved dramatically throughout the years. In 1997, rituximab (Rituxan), a CD20 monoclonal antibody (mAb), became the first mAb approved by the Food and Drug Administration for marketing in the treatment of cancer, specifically targeting B-cell malignancies. Over the last 10 years, rituximab or other mAbs including alemtuzumab and ofatumumab have become an integral part of the standard of care for CLL patients as single agents or in combination with chemotherapy or other immunotherapy. This review discusses the currently approved and novel mAbs for the treatment of CLL. PMID:23561475

  11. Practical Aspects of Allogeneic Hematopoietic Cell Transplantation for Patients with Poor-Risk Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Julio Delgado

    2011-01-01

    Full Text Available Allogeneic hematopoietic cell transplantation has become a viable option for younger patients with poor-risk chronic lymphocytic leukemia. The results obtained with either conventional or reduced-intensity conditioning regimens have been recently evaluated and compared with alternative nontransplant strategies. This manuscript deals with practical aspects of the procedure, including patient and donor selection, conditioning regimen, GVHD prophylaxis, disease monitoring, infectious and noninfectious complications, and timing of the procedure. Finally, we speculate on how we could improve the results obtained with the procedure and new advances currently in clinical trials.

  12. Motivating medical students to learn basic science concepts using chronic myeloid leukemia as an integration theme

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    Sara Teresinha Olalla Saad

    2015-02-01

    Full Text Available Objective: To report on the use of chronic myeloid leukemia as a theme of basic clinical integration for first year medical students to motivate and enable in-depth understanding of the basic sciences of the future physician. Methods: During the past thirteen years we have reviewed and updated the curriculum of the medical school of the Universidade Estadual de Campinas. The main objective of the new curriculum is to teach the students how to learn to learn. Since then, a case of chronic myeloid leukemia has been introduced to first year medical students and discussed in horizontal integration with all themes taught during a molecular and cell biology course. Cell structure and components, protein, chromosomes, gene organization, proliferation, cell cycle, apoptosis, signaling and so on are all themes approached during this course. At the end of every topic approached, the students prepare in advance the corresponding topic of clinical cases chosen randomly during the class, which are then presented by them. During the final class, a paper regarding mutations in the abl gene that cause resistance to tyrosine kinase inhibitors is discussed. After each class, three tests are solved in an interactive evaluation. Results: The course has been successful since its beginning, 13 years ago. Great motivation of those who participated in the course was observed. There were less than 20% absences in the classes. At least three (and as many as nine students every year were interested in starting research training in the field of hematology. At the end of each class, an interactive evaluation was performed and more than 70% of the answers were correct in each evaluation. Moreover, for the final evaluation, the students summarized, in a written report, the molecular and therapeutic basis of chronic myeloid leukemia, with scores ranging from 0 to 10. Considering all 13 years, a median of 78% of the class scored above 5 (min 74%-max 85%, and a median of 67

  13. 5-Azacytidine in chronic myelomonocytic leukemia: case report and review of literature

    Directory of Open Access Journals (Sweden)

    Marianna Criscuolo

    2011-01-01

    Full Text Available

    Hypomethylating drugs are useful in the management of Myelodysplastic syndromes, but  there are only few reports on chronic myelomonocycitic (CMML leukemia patients. We describe our experience in 3 CMML patients treated with azacitidine. Two patients obtained partial response after 4 treatment cycles with only minor toxicity and are in continuous partial response, with stable peripheral blood counts, at 29 and 30 cycles from treatment start.

  14. Advances in the diagnosis and treatment of acute and chronic leukemia in Mexico.

    Science.gov (United States)

    Ruiz-Argüelles, Guillermo José

    2016-04-01

    In the last 60 years, there have been substantial advances regarding the diagnosis and treatment of patients with acute and chronic leukemia in Mexico. Immunologic and molecular classifications of these diseases have improved both diagnosis and therapeutic capabilities. Although the pace of diagnostic and therapeutic advances has been slower compared with developed countries, Mexico is at the forefront among developing countries. Supporting research in these fields is expected to enhance the generation of new knowledge and improve the care of patients suffering from these diseases. PMID:27557388

  15. Regulatory T-cells in chronic lymphocytic leukemia: actor or innocent bystander?

    Science.gov (United States)

    D’Arena, Giovanni; Simeon, Vittorio; D’Auria, Fiorella; Statuto, Teodora; Sanzo, Paola Di; Martino, Laura De; Marandino, Aurelio; Sangiorgio, Michele; Musto, Pellegrino; Feo, Vincenzo De

    2013-01-01

    Regulatory T (Treg) cells are now under extensive investigation in chronic lymphocytic leukemia (CLL). This small subset of T-cells has been, in fact, considered to be involved in the pathogenesis and progression of CLL. However, whether Treg dysregulation in CLL plays a key role or it rather represents a simple epiphenomenon is still matter of debate. In the former case, Treg cells could be appealing for targeting therapies. Finally, Treg cells have also been proposed as a prognostic indicator of the disease clinical course. PMID:23358515

  16. An Urologic Face of Chronic Lymphocytic Leukemia:Sequential Prostatic and Penis Localization

    Directory of Open Access Journals (Sweden)

    Giovanni D'Arena

    2013-01-01

    Full Text Available We report a patient with chronic lymphocytic leukemia (CLL in whom a leukemic involvement of prostate and penis occurred in the advanced phase of his disease. Obstructive urinary symptoms were indicative of prostatic CLL infiltration, followed by the occurrence of an ulcerative lesion on the glans. Histologic examination confirmed  the  neoplastic B-cell infiltration. Both localizations responded to conventional treatments. A review of the literature confirms that leukemic involvement of the genito-urinary system is   uncommon in CLL patients. However, such an involvement should be considered in CLL patients with urologic symptoms and a long history of the disease.

  17. Endobronchial deposits of chronic lymphocytic leukemia - an unusual cause of central airway obstruction.

    Science.gov (United States)

    Maw, Miranda; Harvey, Michael; Harrington, Zinta; Baraket, Melissa; Montgomery, Renn; Williamson, Jonathan

    2015-06-01

    A 66-year-old woman with a background of chronic lymphocytic leukemia (CLL) was admitted to the hospital on several occasions with recurrent episodes of community-acquired pneumonia. Computed tomography and bronchoscopy revealed multiple obstructing endobronchial polyps. Post-obstructive pneumonia together with immunoglobulin G deficiency was considered the most likely cause of these recurrent infections. Bronchoscopy was performed for removal of the critically obstructing lesions. Histopathology revealed replacement of bronchial mucosa with CLL deposits. Despite a brief window of infection-free survival following therapy, she remained susceptible to pneumonia with further hospital admissions and eventually died from her disease. PMID:26090107

  18. Massive splenic infarction and portal vein thrombosis in children with chronic myeloid leukemia.

    Science.gov (United States)

    Aksu, Tekin; Erdem, Arzu Y; Fettah, Ali; Kaçar, Dilek; Avci, Zekai; Yarali, Nese; Tunc, Bahattin

    2014-10-01

    Massive splenic infarction and portal vein thrombosis (PVT) due to chronic myeloid leukemia (CML) is extremely rare. We describe 2 children who were presented with massive splenic infarction and PVT in the course of CML. Massive splenic infarction and PVT treated with splenectomy in one and with medical treatment in another in whom PVT resolved by cytoreductive treatment, led to downsizing of spleen or splenectomy. Splenic infarct and PVT should be considered in CML patients with long-lasting severe abdominal pain despite appropriate medical attempts. Splenectomy should be spared for persistent symptoms and complications.

  19. Magnetic resonance imaging may simulate progressive multifocal leucoencephalopathy in a patient with chronic lymphocytic leukemia after fludarabine therapy

    Directory of Open Access Journals (Sweden)

    Kalita J

    2008-01-01

    Full Text Available A 60-year-old male with chronic lymphatic leukemia (CLL after 6 months of fludarabine therapy was admitted with status epilepticus and developed left hemiplegia. His magnetic resonance imaging revealed multiple T2 hyperintense lesions in the right frontal and left parieto-occipital lesion, simulating progressive multifocal leucoencephalopathy (PML. Cerebrospinal fluid Polymerase Chain Reaction (PCR for JC virus was negative. We suggest the possible role of fludarabine in producing PML-like lesions in patients with Chronic Lymphocytic Leukemia (CLL.

  20. Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia

    Science.gov (United States)

    Brehme, Marc; Koschmieder, Steffen; Montazeri, Maryam; Copland, Mhairi; Oehler, Vivian G.; Radich, Jerald P.; Brümmendorf, Tim H.; Schuppert, Andreas

    2016-04-01

    Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34+ similarity as a disease progression marker to patient-derived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients’ disease history within chronic phase (CP) and significantly separates “early” from “late” CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis.

  1. Therapeutic options for chronic myeloid leukemia: focus on imatinib (Glivec®, Gleevec™

    Directory of Open Access Journals (Sweden)

    Martin Henkes

    2008-03-01

    Full Text Available 1Martin Henkes, 2Heiko van der Kuip, 1Walter E Aulitzky12nd Department of Internal Medicine, Oncology and Hematology, Robert Bosch Hospital, Auerbachstr. 110, Stuttgart, Germany; 2Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, Stuttgart, and University of Tuebingen, GermanyAbstract: Treatment options for chronic myeloid leukemia (CML have changed dramatically during the last decades. Interferon-α treatment and stem cell transplantation (SCT clearly improved survival over conventional chemotherapy and offered the possibility of complete and durable responses. With the advent of the small molecule inhibitor imatinib mesylate (Glivec®, GleevecTM targeting the causative Bcr-Abl oncoprotein, the era of molecular cancer therapy began with remarkable success especially in chronic phase patients. Today, imatinib is the first-line treatment for CML. However, imatinib does not appear to be capable to eliminate all leukemia cells in the patients and pre-existing as well as acquired resistance to the drug has been increasingly recognized. To overcome these problems, several strategies involving dose escalation, combinations with other agents, and novel Bcr-Abl inhibitors have been developed.Keywords: CML therapy, imatinib, SCT, novel kinase inhibitors

  2. Current strategies in the diagnosis and management of chronic neutrophilic leukemia

    Institute of Scientific and Technical Information of China (English)

    Altangerel Otgonbat; Zhao Mingfeng

    2014-01-01

    Objective To review the implications for diagnosis,pathogenesis and potential for new therapeutic option for chronic neutrophilic leukemia (CNL).Data sources Data cited in this review were obtained mainly from PubMed and Medline from 1993 to 2013 and highly regarded older publications were also included.The terms "chronic neutrophilic leukemia" and "diagnosis" were used for the literature search.Study selection We identified,retrieved and reviewed the information on the clinical and laboratory features,the new genetic findings,prognosis and disease evolution and management of CNL.Results The discovery of high-frequency granulocyte-colony stimulating factor receptor (CSF3R) mutations in CNL identifies a new major diagnostic criterion,and lends more specificity to the World Health Organization (WHO) diagnostic criteria for CNL,which are variably applied in routine clinical practice.Conclusions In patients for whom the cause of neutrophilia is not easily discerned,the incorporation of CSF3R mutation testing can be a useful point-of-care diagnostic to evaluate the presence of a clonal myeloid disorder,as well as providing the potential for genetically informed therapy.The oncogenic CSF3R mutations are molecular markers of sensitivity to inhibitors of the SRC family-TNK2 and JAK kinases and may provide a new avenue for therapy.

  3. Role of signaling pathways and miRNAs in chronic lymphocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    LI Pei-pei; WANG Xin

    2013-01-01

    Objective To summarize the recent findings of dysregulation of signaling pathways and miRNAs in chronic lymphocytic leukemia (CLL).Data sources We searched PubMed database with the keywords "chronic lymphocytic leukemia","signal pathway",or "miRNA" for relevant articles in recent years.Study selection Research articles and reviews about signaling pathways and miRNAs in CLL were chosen for review.Results Dysregulation of signaling pathways,such as B cell receptor,toll-like receptor,PI3K,nuclear factor KB,notch signaling pathway,Wnt/Fzd signaling pathway,and Hedgehog and Janus kinases/signal transducers and activators of transcription signaling pathway,as the terminal events of the aberrant gene expression and the pro-survival effects of microenvironment,plays a crucial role in the process of CLL.miRNAs,a novel found noncoding RNA,which regulate gene expression at transcription or post-transcription level and correlate with pathogenesis of CLL provide us new avenues to better evaluating prognosis and therapy of it.Conclusion Further investigation of the dysregulation of signaling pathways and miRNAs and their relationship may provide us a new prospective to understand the pathogenesis of CLL and may provide us new strategies to resolve the clinical nodi in treatment of CLL.

  4. First-line therapy of chronic myeloid leukemia – focus on dasatinib

    Directory of Open Access Journals (Sweden)

    Amrein PC

    2012-04-01

    Full Text Available Philip C AmreinHematology-Oncology, Massachusetts General Hospital, Boston, USAAbstract: Dasatinib is a broad spectrum, ATP-competitive, tyrosine kinase inhibitor with low nM activity against Bcr-Abl, Src, and other tyrosine kinases. This activity has allowed dasatinib to emerge as one of the most effective agents in the treatment of chronic myeloid leukemia (CML, and dasatinib has become the third drug over the past 10 years to be FDA approved for first line therapy in this setting. This review consists of papers and reports that recount the recent dramatic progress that has been made in the understanding of CML on a molecular basis leading up to the new targeted therapies, especially the use of dasatinib. As with any drug, treatment with dasatinib has risks and side effects, especially pleural effusions and anti-platelet effects, as outlined in recently published studies. Of interest are the reports of alternative doses and schedules that may be able to circumvent some of these side effects without compromising the effectiveness of this drug. This review outlines the mode of action, pharmacology, effectiveness, and safety of dasatinib in the treatment of CML, and by comparing dasatinib directly with the other tyrosine kinase inhibitors effective in CML, it describes the place in therapy that dasatinib currently holds.Keywords: dasatinib, CML, chronic myeloid leukemia 

  5. Leukemia cutis

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    Varuna Mallya

    2015-01-01

    Full Text Available Patients with leukemia may show involvement of the skin. This skin involvement can be due to infiltration of skin by leukemic cells or it may be a part of nonspecific cutaneous manifestations. Leukemia cutis is the infiltration of neoplastic leucocytes or their precursors into the skin resulting in extensive clinical manifestations. Described mostly in acute myeloid leukemia and acute myelocytic monocytic leukemia, it is rare in chronic myeloid leukemia and is seen mostly during the blast crises. Its presence signals poor prognosis.

  6. Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML

    Science.gov (United States)

    2016-08-03

    Relapsed Acute Lymphoblastic Leukemia (ALL); Refractory Acute Lymphoblastic Leukemia (ALL); Relapsed Acute Myelogenous Leukemia (AML); Refractory Acute Myelogenous Leukemia (AML); Relapsed Mixed Lineage Leukemia; Refractory Mixed Lineage Leukemia; Relapsed Biphenotypic Leukemia; Refractory Biphenotypic Leukemia; Chronic Myelogenous Leukemia (CML) in Blast Crisis

  7. The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2

    Directory of Open Access Journals (Sweden)

    Winger Jonathan A

    2009-02-01

    Full Text Available Abstract Background Imatinib represents the first in a class of drugs targeted against chronic myelogenous leukemia to enter the clinic, showing excellent efficacy and specificity for Abl, Kit, and PDGFR kinases. Recent screens carried out to find off-target proteins that bind to imatinib identified the oxidoreductase NQO2, a flavoprotein that is phosphorylated in a chronic myelogenous leukemia cell line. Results We examined the inhibition of NQO2 activity by the Abl kinase inhibitors imatinib, nilotinib, and dasatinib, and obtained IC50 values of 80 nM, 380 nM, and >100 μM, respectively. Using electronic absorption spectroscopy, we show that imatinib binding results in a perturbation of the protein environment around the flavin prosthetic group in NQO2. We have determined the crystal structure of the complex of imatinib with human NQO2 at 1.75 Å resolution, which reveals that imatinib binds in the enzyme active site, adjacent to the flavin isoalloxazine ring. We find that phosphorylation of NQO2 has little effect on enzyme activity and is therefore likely to regulate other aspects of NQO2 function. Conclusion The structure of the imatinib-NQO2 complex demonstrates that imatinib inhibits NQO2 activity by competing with substrate for the active site. The overall conformation of imatinib when bound to NQO2 resembles the folded conformation observed in some kinase complexes. Interactions made by imatinib with residues at the rim of the active site provide an explanation for the binding selectivity of NQO2 for imatinib, nilotinib, and dasatinib. These interactions also provide a rationale for the lack of inhibition of the related oxidoreductase NQO1 by these compounds. Taken together, these studies provide insight into the mechanism of NQO2 inhibition by imatinib, with potential implications for drug design and treatment of chronic myelogenous leukemia in patients.

  8. Proteomic analysis of nuclear matrix proteins during arsenic trioxide induced apoptosis in leukemia K562 cells

    Institute of Scientific and Technical Information of China (English)

    WANG Zi-hui; YU Ding; CHEN Yan; HAO Jian-zhong

    2005-01-01

    Background Arsenic trioxide (As2O3) has been identified as a very potent anti-acute leukemic agent. However its role in apoptosis needs to be elucidated. As2O3 interferes with the proliferation and survival of tumor cells via a variety of mechanisms. Drug-target interactions at the level of nuclear matrix (NM) may be critical events in the induction of cell death by As2O3. This study dealt with As2O3-target interactions at the level of NM in chronic myelogenous leukemia cell line K562 by proteomics. Methods K562 cells were cultured in MEM and treated with different concentrations of As2O3. The nuclear matrix proteins were analyzed by high-resolution two-dimensional gel electrophoresis and computer-assisted image analysis. Results As2O3 significantly inhibited the growth of chronic myelogenous leukemia cell line K562 at low concentrations. While more than 200 protein spots were shared among the nuclear matrices, about 18 distinct spots in the nuclear matrices were found characteristic for As2O3 treated cells. Conclusions: As2O3 induces apoptosis in K562 cells in a dose and time-dependent manner. Our results demonstrated that for the detection of the onset of apoptosis, the alteration in the composition of nuclear matrix proteins was a more sensitive indicator than nucleosomal DNA fragmentation test. These results indicated that As2O3 might be clinically useful in the treatment of chronic myelogenous leukemia. The changes of nuclear matrix proteins in the treated cells can be used as a useful indicator for this treatment.

  9. Interleukin-2 and its application in the treatment of patients with acute myelogenous leukemia%白细胞介素-2的抗肿瘤机制及其在急性髓系白血病中的临床应用

    Institute of Scientific and Technical Information of China (English)

    顾敏; 秘营昌

    2008-01-01

    白细胞介素-2(IL-2)作为机体免疫网络中最重要的起调节作用的细胞因子,由活化的T或NK细胞以自分泌或旁分泌方式产生,在激活和维持免疫应答以及促进淋巴细胞发育中起着重要的作用,并已应用于肿瘤的临床治疗及试验性研究中,现就IL-2的抗肿瘤机制及其在急性髓系白血病(AML)中的临床应用作一综述.%As one of the cytokines which play important role in the regulation of immune system,such as activating and maintaining immune response and promoting lymphocyte development,interleukin-2 is secreted by activated T cell or NK cell and has been extensively applied to clinical therapy and laboratory research. This paper is maily about the anti-tumor mechanism of interleukin-2 and its application in the treatment of patients with acute myelogenous leukemia.

  10. Association of Bax Expression and Bcl2/Bax Ratio with Clinical and Molecular Prognostic Markers in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Vucicevic Ksenija

    2016-04-01

    Full Text Available Background: In chronic lymphocytic leukemia (CLL, in vivo apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the Bcl2 family members play a central role.

  11. OCT-1, ABCB1, and ABCG2 Expression in Imatinib-Resistant Chronic Myeloid Leukemia Treated with Dasatinib or Nilotinib

    OpenAIRE

    Kim, Yeo-Kyeoung; Lee, Seung-Shin; Jeong, Sung-Hoon; Ahn, Jae-Sook; Yang, Deok-Hwan; Lee, Je-Jung; Shin, Myung-Geun; Kim, Hyeoung-Joon

    2014-01-01

    This study explored drug transporter expression levels and their impact on clinical response to imatinib and second-generation tyrosine kinase inhibitors (TKIs) in imatinib- resistant chronic myeloid leukemia (CML). Imatinib-resistant chronic phase CML patients treated with dasatinib (n=10) and nilotinib (n=12) were enrolled. The mRNA expression of the OCT-1, ABCG2, and ABCB1 genes was quantified by using paired bone marrow samples obtained before administering imatinib and at the point of de...

  12. Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States

    OpenAIRE

    Padula, William V.; Larson, Richard A.; Dusetzina, Stacie B.; Apperley, Jane F.; Baccarani, Michele; Eigendorff, Ekkehard; Guilhot, Joelle; Guilhot, Francois; Hehlmann, Rudiger; Mahon, Francois-Xavier; Martinelli, Giovanni; Mayer, Jiri; Martin C Müller; Niederwieser, Dietger; Saussele, Susanne

    2016-01-01

    Background: We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib’s price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectivene...

  13. New Mouse Models to Investigate the Efficacy of Drug Combinations in Human Chronic Myeloid Leukemia.

    Science.gov (United States)

    Lin, Hanyang; Woolfson, Adrian; Jiang, Xiaoyan

    2016-01-01

    Chronic myeloid leukemia (CML) comprises a simple and effective paradigm for generating new insights into the cellular origin, pathogenesis, and treatment of many types of human cancer. In particular, mouse models of CML have greatly facilitated the understanding of the underlying molecular mechanisms and pathogenesis of this disease and have led to the identification of new drug targets that in some cases offer the possibility of functional cure. There are currently three established CML mouse models: the BCR-ABL transgenic model, the BCR-ABL retroviral transduction/transplantation model, and the xenotransplant immunodeficient model. Each has its own unique advantages and disadvantages. Depending on the question of interest, some models may be more appropriate than others. In this chapter, we describe a newly developed xenotransplant mouse model to determine the efficacy of novel therapeutic agents, either alone or in combination. The model facilitates the evaluation of the frequency of leukemic stem cells with long-term leukemia-initiating activity, a critical subcellular population that causes disease relapse and progression, through the utilization of primary CD34(+) CML stem/progenitor cells obtained from CML patients at diagnosis and prior to drug treatment. We have also investigated the effectiveness of new combination treatment strategies designed to prevent the development of leukemia in vivo using BCR-ABL (+) blast crisis cells as a model system. These types of in vivo studies are important for the prediction of individual patient responses to drug therapy, and have the potential to facilitate the design of personalized combination therapy strategies. PMID:27581149

  14. Sensitive DNA impedance biosensor for detection of cancer, chronic lymphocytic leukemia, based on gold nanoparticles/gold modified electrode

    Energy Technology Data Exchange (ETDEWEB)

    Ensafi, Ali A., E-mail: ensafi@cc.iut.ac.ir [Department of Chemistry, Isfahan University of Technology, Isfahan (Iran, Islamic Republic of); Taei, M. [Department of Chemistry, Isfahan University of Technology, Isfahan (Iran, Islamic Republic of); Rahmani, H.R. [Department of Animal Science, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Khayamian, T. [Department of Chemistry, Isfahan University of Technology, Isfahan (Iran, Islamic Republic of)

    2011-10-01

    Highlights: > Chronic lymphocytic leukemia causes an increase in the number of white blood cells. > We introduced a highly sensitive biosensor for the detection of chronic lymphocytic leukemia. > A suitable 25-mer ssDNA probe was immobilized on the surface of the gold nanoparticles. > We used electrochemical impedance spectroscopy as a suitable tool for the detection. > Detection of chronic lymphocytic leukemia in blood sample was checked using the sensor. - Abstract: A simple and sensitive DNA impedance sensor was prepared for the detection of chronic lymphocytic leukemia. The DNA electrochemical biosensor is worked based on the electrochemical impedance spectroscopic (EIS) detection of the sequence-specific DNA related to chronic lymphocytic leukemia. The ssDNA probe was immobilized on the surface of the gold nanoparticles. Compared to the bare gold electrode, the gold nanoparticles-modified electrode could improve the density of the probe DNA attachment and hence the sensitivity of the DNA sensor greatly. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy were performed in a solution containing 1.0 mmol L{sup -1} K{sub 3}[Fe(CN){sub 6}]/K{sub 4}[Fe(CN){sub 6}] and 50 mmol L{sup -1} phosphate buffer saline pH 6.87 plus 50 mmol L{sup -1} KCl. In the CV studied, the potential was cycled from 0.0 to +0.65 V with a scan rate of 50 mV s{sup -1}. Using EIS, the difference of the electron transfer resistance ({Delta}R{sub et}) was linear with the logarithm of the complementary oligonucleotides sequence concentrations in the range of 7.0 x 10{sup -12}-2.0 x 10{sup -7} mol L{sup -1}, with a detection limit of 1.0 x 10{sup -12} mol L{sup -1}. In addition, the DNA sensor showed a good reproducibility and stability during repeated regeneration and hybridization cycles.

  15. Aberrant activation of CaMKIIγ accelerates chronic myeloid leukemia blast crisis.

    Science.gov (United States)

    Gu, Y; Zheng, W; Zhang, J; Gan, X; Ma, X; Meng, Z; Chen, T; Lu, X; Wu, Z; Huang, W; Xu, R

    2016-06-01

    Blast crisis (BC) is the final deadly phase of chronic myeloid leukemia (CML), but its molecular basis remains poorly understood. Here, we show that CML BC is regulated by calcium-calmodulin-dependent kinase IIγ (CaMKIIγ). Genetic deletion of CaMKIIγ greatly inhibits disease progression via selectively impairing the self-renewal of leukemia stem cells (LSCs) in mouse models, whereas overexpression of CaMKIIγ has the opposite effects. In human CML, phosphorylated CaMKIIγ abundance is significantly associated with BC. Moreover, CaMKIIγ phosphorylates and reduces the nuclear cyclin-dependent kinase inhibitor p27Kip1, a critical brake that maintains LSC quiescence. These findings suggest that CaMKIIγ might be an important switch for the transition of CML BC and identify a unique mechanism by which CaMKIIγ promotes the self-renewal of LSCs by deceasing nuclear p27Kip1 to wake up dormant LSCs. Therefore, CaMKIIγ may provide a new therapeutic target to treat CML BC. PMID:27012864

  16. B cell receptor pathway in chronic lymphocytic leukemia: specific role of CC-292

    Directory of Open Access Journals (Sweden)

    Arnason JE

    2014-01-01

    Full Text Available Jon E Arnason,1 Jennifer R Brown21Beth Israel Deaconess Medical Center, 2CLL Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USAAbstract: Chronic lymphocytic leukemia (CLL is the most common adult leukemia. The current treatment paradigm involves the use of chemoimmunotherapy, when patients develop an indication for therapy. With this strategy, a majority of patients will obtain a remission, though cure remains elusive. While treatable, the majority of CLL patients will die of complications of their disease. Recent advances in the understanding of the importance of the B cell receptor (BCR pathway in CLL have led to the development of a number of agents targeting this pathway. In this review, we discuss recent developments in the targeting of the BCR pathway, with a focus on CC-292. CC-292 covalently binds to Bruton's tyrosine kinase, a key mediator of BCR signaling, and has demonstrated preclinical and clinical activity in CLL, with acceptable tolerability. Based on the success of CC-292 and other inhibitors of the BCR pathway, these agents are being investigated in combination with standard therapy, with the hope that they will increase the depth and length of response, without significant toxicity.Keywords: Bruton's tyrosine kinase inhibitor, ibrutinib

  17. Occupation and leukemia in Nordic countries

    DEFF Research Database (Denmark)

    Talibov, Madar; Kautiainen, Susanna; Martinsen, Jan Ivar;

    2012-01-01

    We studied occupational variation of the risk of acute myeloid leukemia, chronic lymphocytic leukemia, and other leukemia in Nordic countries.......We studied occupational variation of the risk of acute myeloid leukemia, chronic lymphocytic leukemia, and other leukemia in Nordic countries....

  18. Bilateral central retinal vein occlusion as presenting feature of chronic Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Subina Narang

    2016-01-01

    Full Text Available Central retinal vein occlusion (CRVO is a common pathology of the retinal vasculature. Patients with CRVO usually present with a drop in visual acuity. The condition bears no specific therapy; treatment is aimed at the management of potentially blinding complications, of which there are many. With majority of cases being unilateral, bilateral CRVO is usually associated with an underlying systemic illness such as a hyperviscosity syndrome. Here, we present a case of a patient, who presented with a bilateral drop in vision diagnosed as bilateral CRVO on ophthalmic evaluation. Systemic workup revealed the presence of an underlying undiagnosed chronic myeloid leukemia. An initial presentation to the ophthalmologist is a rare occurrence in leukemic patients. This case report highlights the role of the ophthalmologist in diagnosing a potentially life-threatening hematological illness.

  19. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Agathangelidis, Andreas; Darzentas, Nikos; Hadzidimitriou, Anastasia;

    2012-01-01

    Mounting evidence indicates that grouping of chronic lymphocytic leukemia (CLL) into distinct subsets with stereotyped BCRs is functionally and prognostically relevant. However, several issues need revisiting, including the criteria for identification of BCR stereotypy and its actual frequency...... as well as the identification of "CLL-biased" features in BCR Ig stereotypes. To this end, we examined 7596 Ig VH (IGHV-IGHD-IGHJ) sequences from 7424 CLL patients, 3 times the size of the largest published series, with an updated version of our purpose-built clustering algorithm. We document that CLL may...... be subdivided into 2 distinct categories: one with stereotyped and the other with nonstereotyped BCRs, at an approximate ratio of 1:2, and provide evidence suggesting a different ontogeny for these 2 categories. We also show that subset-defining sequence patterns in CLL differ from those underlying BCR...

  20. Ibrutinib: a novel Bruton's tyrosine kinase inhibitor with outstanding responses in patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Barrientos, Jacqueline; Rai, Kanti

    2013-08-01

    New treatment options are urgently needed for patients with relapsed chronic lymphocytic leukemia (CLL) who fail to respond to currently available therapies or cannot achieve a sustained response. Moreover, targeted agents with less myelotoxicity are necessary to treat patients with multiple comorbidities who would otherwise be unable to tolerate standard regimens. Ibrutinib, a Bruton's tyrosine kinase inhibitor, has shown highly encouraging results in phase I/II trials in patients with treatment-naive, relapsed and refractory CLL even in the presence of high risk disease or poor prognostic markers. In phase I/II trials, ibrutinib 420 mg or 840 mg - given continuously as single agent or at a dose of 420 mg daily in combination with a monoclonal antibody or chemoimmunotherapy - has been associated with high response rates and durable clinical remissions. Phase II and III trials are currently under way for treatment-naive patients, relapsed/refractory patients, and for those patients harboring a 17p deletion.

  1. Idelalisib for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma.

    Science.gov (United States)

    Barrientos, Jacqueline C

    2016-09-01

    Idelalisib is a first-in-class selective oral PI3Kδ inhibitor for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma, a predominantly elderly population with high comorbidity. The drug promotes apoptosis in primary CLL cells ex vivo, independent of common prognostic markers and inhibits CLL cell homing, migration and adhesion to cells in the microenvironment. Idelalisib has shown efficacy with acceptable safety as monotherapy and combination therapy in relapsed/refractory CLL. Idelalisib has clinical activity in patients with CLL with del(17p). The development of other novel B-cell-targeted agents provides the opportunity to evaluate additional idelalisib treatment combinations for their potential to further improve outcomes in CLL/small lymphocytic lymphoma.

  2. Idelalisib for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma.

    Science.gov (United States)

    Barrientos, Jacqueline C

    2016-09-01

    Idelalisib is a first-in-class selective oral PI3Kδ inhibitor for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma, a predominantly elderly population with high comorbidity. The drug promotes apoptosis in primary CLL cells ex vivo, independent of common prognostic markers and inhibits CLL cell homing, migration and adhesion to cells in the microenvironment. Idelalisib has shown efficacy with acceptable safety as monotherapy and combination therapy in relapsed/refractory CLL. Idelalisib has clinical activity in patients with CLL with del(17p). The development of other novel B-cell-targeted agents provides the opportunity to evaluate additional idelalisib treatment combinations for their potential to further improve outcomes in CLL/small lymphocytic lymphoma. PMID:27324214

  3. Drug Target Optimization in Chronic Myeloid Leukemia Using Innovative Computational Platform

    Science.gov (United States)

    Chuang, Ryan; Hall, Benjamin A.; Benque, David; Cook, Byron; Ishtiaq, Samin; Piterman, Nir; Taylor, Alex; Vardi, Moshe; Koschmieder, Steffen; Gottgens, Berthold; Fisher, Jasmin

    2015-02-01

    Chronic Myeloid Leukemia (CML) represents a paradigm for the wider cancer field. Despite the fact that tyrosine kinase inhibitors have established targeted molecular therapy in CML, patients often face the risk of developing drug resistance, caused by mutations and/or activation of alternative cellular pathways. To optimize drug development, one needs to systematically test all possible combinations of drug targets within the genetic network that regulates the disease. The BioModelAnalyzer (BMA) is a user-friendly computational tool that allows us to do exactly that. We used BMA to build a CML network-model composed of 54 nodes linked by 104 interactions that encapsulates experimental data collected from 160 publications. While previous studies were limited by their focus on a single pathway or cellular process, our executable model allowed us to probe dynamic interactions between multiple pathways and cellular outcomes, suggest new combinatorial therapeutic targets, and highlight previously unexplored sensitivities to Interleukin-3.

  4. Bilateral Central Retinal Vein Occlusion as Presenting Feature of Chronic Myeloid Leukemia.

    Science.gov (United States)

    Narang, Subina; Gupta, Panchmi; Sharma, Anuj; Sood, Sunandan; Palta, Anshu; Goyal, Shilpa

    2016-01-01

    Central retinal vein occlusion (CRVO) is a common pathology of the retinal vasculature. Patients with CRVO usually present with a drop in visual acuity. The condition bears no specific therapy; treatment is aimed at the management of potentially blinding complications, of which there are many. With majority of cases being unilateral, bilateral CRVO is usually associated with an underlying systemic illness such as a hyperviscosity syndrome. Here, we present a case of a patient, who presented with a bilateral drop in vision diagnosed as bilateral CRVO on ophthalmic evaluation. Systemic workup revealed the presence of an underlying undiagnosed chronic myeloid leukemia. An initial presentation to the ophthalmologist is a rare occurrence in leukemic patients. This case report highlights the role of the ophthalmologist in diagnosing a potentially life-threatening hematological illness. PMID:27555710

  5. Complex Variant t(9;22 Chromosome Translocations in Five Cases of Chronic Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Ana Valencia

    2009-01-01

    Full Text Available The Philadelphia (Ph1 chromosome arising from the reciprocal t(9;22 translocation is found in more than 90% of chronic myeloid leukemia (CML patients and results in the formation of the chimeric fusion gene BCR-ABL. However, a small proportion of patients with CML have simple or complex variants of this translocation, involving various breakpoints in addition to 9q34 and 22q11. We report five CML cases carrying variant Ph translocations involving both chromosomes 9 and 22 as well as chromosomes 3, 5, 7, 8, or 10. G-banding showed a reciprocal three-way translocation involving 3q21, 5q31, 7q32, 8q24, and 10q22 bands. BCR-ABL fusion signal on der(22 was found in all of the cases by FISH.

  6. Increased oxidative damage associated with unfavorable cytogenetic subgroups in chronic lymphocytic leukemia.

    Science.gov (United States)

    Collado, Rosa; Ivars, David; Oliver, Isabel; Tormos, Carmen; Egea, Mercedes; Miguel, Amparo; Sáez, Guillermo T; Carbonell, Félix

    2014-01-01

    Oxidative stress contributes to genomic instability in chronic lymphocytic leukemia (CLL), but its relationship with the acquisition of specific chromosomal abnormalities is unknown. We recruited 55 untreated CLL patients and assessed 8-oxo-2'-deoxyguanosine (8-oxo-dG), glutathione, and malondialdehyde (MDA) levels, and we compared them among the cytogenetic subgroups established using fluorescence in situ hybridization (FISH). Significant increases in 8-oxo-dG and/or MDA were observed in patients with unfavorable cytogenetic aberrations (17p and 11q deletions) compared to the 13q deletion group. TP53 deletion patients exhibited a diminished DNA repair efficiency. Finally, cases with normal FISH also showed enhanced 8-oxo-dG, which could result in adverse outcomes.

  7. Chronic lymphocytic leukemia and myeloproliferative neoplasms concurrently diagnosed: clinical and biological characteristics.

    Science.gov (United States)

    Todisco, Gabriele; Manshouri, Taghi; Verstovsek, Srdan; Masarova, Lucia; Pierce, Sherry A; Keating, Michael J; Estrov, Zeev

    2016-05-01

    Chronic lymphocytic leukemia (CLL) and myeloproliferative neoplasms (MPN) may occur concomitantly. However, little is known about the pathobiological characteristics and interaction between the neoplastic clones in these rare cases of coinciding malignancies. We retrospectively examined the clinical and biological characteristics of 13 patients with concomitant CLL and MPN--eight primary myelofibrosis (PMF), three essential thrombocytosis (ET), and two polycythemia vera (PV)--who presented to our institution between 1998 and 2014, and tested all patients for MPN-specific aberrations, such as JAK2, MPL and CALR mutations. Along with epidemiological and molecular characterization of this rare condition, we found that JAK2 mutation can be detected 9 years prior to PMF diagnosis, suggesting that PMF clinical phenotype may require several years to develop and CLL/MPN clinical co-occurrence might be sustained by common molecular events. Some features of these patients suggest that pathobiologies of these diseases might be intertwined. PMID:26402369

  8. Regulatory T-Cells in Chronic Lymphocytic Leukemia and Autoimmune Diseases

    Science.gov (United States)

    D’Arena, Giovanni; Rossi, Giovanni; Vannata, Barbara; Deaglio, Silvia; Mansueto, Giovanna; D’Auria, Fiorella; Statuto, Teodora; Simeon, Vittorio; De Martino, Laura; Marandino, Aurelio; Del Poeta8, Giovanni; De Feo, Vincenzo; Musto, Pellegrino

    2012-01-01

    Regulatory T-cells (Tregs) constitute a small subset of cells that are actively involved in maintaining self-tolerance, in immune homeostasis and in antitumor immunity. They are thought to play a significant role in the progression of cancer and are generally increased in patient with chronic lymphocytic leukemia (CLL). Their number correlates with more aggressive disease status and is predictive of the time to treatment, as well. Moreover, it is now clear that dysregulation in Tregs cell frequency and/or function may result in a plethora of autoimmune diseases, including multiple sclerosis, type 1 diabetes mellitus, myasthenia gravis, systemic lupus erythematosus, autoimmune lymphoproliferative disorders, rheumatoid arthritis, and psoriasis. Efforts are made aiming to develop approaches to deplete Tregs or inhibit their function in cancer and autoimmune disorders, as well. PMID:22973497

  9. Leucine replaced by methionine at 273 position in chronic myeloid leukemia: Knowns and unknowns…

    Directory of Open Access Journals (Sweden)

    Aditi Harsh Thanky

    2016-01-01

    Full Text Available Chronic myeloid leukemia is a clonal bone marrow stem cell disorder characterized by the presence of Philadelphia chromosome t(9;22(q34;q11 leading to fusion oncogene BCR-ABL. Tyrosine kinase inhibitors (TKIs act by competitively inhibiting BCR-ABL oncoprotein with significant response rates. However, up to 30% of patients fail to achieve complete cytogenetic remission on 1st line TKI imatinib, one of the reasons being mutations in BCR-ABL kinase domain leading to imatinib resistance. Over 80 such mutations have been documented in the literature; however, some of the rare mutations still remain to be studied for their impact in development of resistance and their responsiveness to currently available therapeutic options. Here, we report one such case of a rare mutation leucine replaced by methionine at 273 position and its clinical implications.

  10. Chronic Myeloid Leukemia with Extramedullary Blast Crisis: Two Unusual Sites with Review of Literature.

    Science.gov (United States)

    Sahu, Kamal Kant; Malhotra, Pankaj; Uthamalingam, Preithy; Prakash, Gaurav; Bal, Amanjit; Varma, Neelam; Varma, Subhash Chandar

    2016-06-01

    Extramedullary blast crisis (EBC) in chronic myeloid leukemia (CML) is a rare phenomenon and represents infiltration of leukemic blasts in areas other than bone marrow. Lymph node is the most common site of involvement by EBC. We herein present a case of CML who suffered from two discrete episodes of EBC at atypical locations (scalp and paravertebral) within an interval duration of nine months. A-38-year-old female was diagnosed as a case of CML with extramedullary blast crisis in scalp at presentation. She received treatment with imatinib 600 mg once daily through Novartis Oncology Access Program (NOA). She achieved hematological remission. However nine months later she was readmitted with spinal shock due to cord compression secondary to paraspinal chloroma. She was started on tablet Nilotinib in view of failure to 1st line therapy. Her compressive myelopathy was treated with pulses of high dose dexamethasone. However soon she died due to pneumonia. PMID:27408365

  11. [Modern therapy of chronic myeloid leukemia: an example for paradigma shift in hemato-oncology].

    Science.gov (United States)

    Leitner, A A; Hehlmann, R

    2011-02-01

    Chronic myeloid leukemia (CML) is exceptional amongst neoplasias since its underlying pathomechanism has been elucidated, and potent well tolerated targeted drugs, the tyrosine kinase inhibitors (TKI), are available for treatment. They convincingly improve prognosis while retaining good quality of life. Aims of therapy are complete remissions as well as prolongation of life and cure. Imatinib 400 mg per day is current standard therapy. There are hints for a better outcome with a higher initial imatinib dose or with combination therapy. Even after achievement of complete molecular response continuous therapy might be necessary in most cases. In case of imatinib intolerance or failure, the second generation TKI dasatinib and nilotinib and allogeneic stem cell transplantation are available. The use of second generation TKI as first line treatment might further improve prognosis. The therapeutic response should be regularly monitored according to international recommendations. PMID:21225238

  12. Eryptotic Phenotype in Chronic Myeloid Leukemia: Contribution of Neutrophilic Cathepsin G

    Directory of Open Access Journals (Sweden)

    Rukmini Govekar

    2012-01-01

    Full Text Available In pathological conditions with concurrent neutrophilia, modifications of erythrocyte membrane proteins are reported. In chronic myeloid leukemia (CML, a myeloproliferative disease wherein neutrophilia is accompanied by enhanced erythrophagocytosis, we report for the first time excessive cleavage of erythrocyte band 3. Distinct fragments of band 3 serve as senescent cell antigens leading to erythrophagocytosis. Using immunoproteomics, we report the identification of immunogenic 43 kDa fragment of band 3 in 68% of CML samples compared to their detection in only 38% of healthy individuals. Thus, excessive fragmentation of band 3 in CML, detected in our study, corroborated with the eryptotic phenotype. We demonstrate the role of neutrophilic cathepsin G, detected as an immunogen on erythrocyte membrane, in band 3 cleavage. Cathepsin G from serum adsorbs to the erythrocyte membrane to mediate cleavage of band 3 and therefore contribute to the eryptotic phenotype in CML.

  13. [Modern therapy of chronic myeloid leukemia: an example for paradigma shift in hemato-oncology].

    Science.gov (United States)

    Leitner, A A; Hehlmann, R

    2011-02-01

    Chronic myeloid leukemia (CML) is exceptional amongst neoplasias since its underlying pathomechanism has been elucidated, and potent well tolerated targeted drugs, the tyrosine kinase inhibitors (TKI), are available for treatment. They convincingly improve prognosis while retaining good quality of life. Aims of therapy are complete remissions as well as prolongation of life and cure. Imatinib 400 mg per day is current standard therapy. There are hints for a better outcome with a higher initial imatinib dose or with combination therapy. Even after achievement of complete molecular response continuous therapy might be necessary in most cases. In case of imatinib intolerance or failure, the second generation TKI dasatinib and nilotinib and allogeneic stem cell transplantation are available. The use of second generation TKI as first line treatment might further improve prognosis. The therapeutic response should be regularly monitored according to international recommendations.

  14. Cytosine arabinoside and daunorubicin induction therapy in a patient with acute myeloid leukemia on chronic hemodialysis.

    Science.gov (United States)

    Krashin, Eilon; Dolberg, Osnat J; Hellmann, Ilana; Huitema, Alwin D R; Rosing, Hilde; Ellis, Martin

    2016-09-01

    The combination of daunorubicin and cytarabine is the cornerstone of induction therapy for acute myeloid leukemia (AML). Little data are available on the optimal chemotherapy regimen for patients with AML and advanced renal failure, with some authors recommending administration of reduced daunorubicin doses. We report the case of a 54-year-old AML patient on chronic hemodialysis who was treated with a modified induction regimen with reduced-dose daunorubin. Daunorubicin levels were measured during the treatment schedule. Although daunorubicin terminal t1/2 appears to be unaffected in hemodialysis patients, the estimated 0-23 h area under the curve was comparable with that of patients receiving full-dose daunorubicin. Therefore, dose adjustment in this patient group may be prudent. PMID:27254285

  15. Dynamic Length Changes of Telomeres and Their Nuclear Organization in Chronic Myeloid Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Samassekou, Oumar [Manitoba Institute of Cell Biology, Cancer Care Manitoba, Department of Physiology, University of Manitoba, Winnipeg, Manitoba R3E 0V9 (Canada)

    2013-08-22

    Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the t(9;22) translocation. As in most cancers, short telomeres are one of the features of CML cells, and telomere shortening accentuates as the disease progresses from the chronic phase to the blastic phase. Although most individual telomeres are short, some of them are lengthened, and long individual telomeres occur non-randomly and might be associated with clonal selection. Telomerase is the main mechanism used to maintain telomere lengths, and its activity increases when CML evolves toward advanced stages. ALT might be another mechanism employed by CML cells to sustain the homeostasis of their telomere lengths and this mechanism seems predominant at the early stage of leukemogenesis. Also, telomerase and ALT might jointly act to maintain telomere lengths at the chronic phase, and as CML progresses, telomerase becomes the major mechanism. Finally, CML cells display an altered nuclear organization of their telomeres which is characterized by the presence of high number of telomeric aggregates, a feature of genomic instability, and differential positioning of telomeres. CML represents a good model to study mechanisms responsible for dynamic changes of individual telomere lengths and the remodeling of telomeric nuclear organization throughout cancer progression.

  16. Influence of late treatment on how chronic myeloid leukemia responds to imatinib

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    Ana Carolina Costa Scerni

    2009-01-01

    Full Text Available INTRODUCTION: In Brazil, patients with chronic myeloid leukemia (CML in the chronic phase were not given first-line imatinib treatment until 2008. Therefore, there was a long period of time between diagnosis and the initiation of imatinib therapy for many patients. This study aims to compare the major molecular remission (MMR rates of early versus late imatinib therapy in chronic phase CML patients. METHODS: Between May 2002 and November 2007, 44 patients with chronic phase CML were treated with second-line imatinib therapy at the Hematology Unit of the Ophir Loyola Hospital (Belém, Pará, Brazil. BCR-ABL transcript levels were measured at approximately six-month intervals using quantitative polymerase chain reaction. RESULTS: The early treatment group presented a 60% probability of achieving MMR, while the probability for those patients who received late treatment was 40%. The probability of either not achieving MMR within one year of the initiation of imatinib therapy or losing MMR was higher in patients who received late treatment (79%, compared with patients who received early treatment (21%, odds ratio=5.75, P=0.012. The probability of maintaining MMR at 30 months of treatment was 80% in the early treatment group and 44% in the late treatment group (P=0.0005. CONCLUSIONS: For CML patients in the chronic phase who were treated with second-line imatinib therapy, the probability of achieving and maintaining MMR was higher in patients who received early treatment compared with those patients for whom the time interval between diagnosis and initiation of imatinib therapy was longer than one year.

  17. Dasatinib: the emerging evidence of its potential in the treatment of chronic myeloid leukemia

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    Sonya Haslam

    2005-03-01

    Full Text Available Sonya HaslamCore Medical Publishing, Mere House, Brook Street, Knutsford, Cheshire WA16 8GP, UKIntroduction: Current therapy options for chronic myeloid leukemia (CML include conventional chemotherapy, allogeneic stem cell transplant, interferon-alfa, and imatinib mesylate, which has recently achieved gold standard status. Although the majority of patients initially respond well to treatment with imatinib, wider clinical experience with this drug has resulted in the development of imatinib resistance being increasingly documented. There is therefore an unmet medical need for novel therapies to override imatinib resistance in CML.Aims: This review summarizes the emerging evidence for the potential use of dasatinib in the treatment of imatinib-resistant CML. Disease and treatment: Dasatinib is a novel small molecule that has shown potent antileukemic activity in imatinib-resistant cell lines, malignant marrow cells isolated from patients with imatinib-resistant CML, and in mouse xenograft models of imatinib-resistant CML. Preliminary data from an initial phase I dose escalation trial have been encouraging, indicating that dasatinib is generally well tolerated and produces hematologic and cytogenetic responses in patients with imatinib-resistant CML in all phases of the disease. The maximum tolerated dose (MTD has not yet been reached, and dose escalation continues to determine the dose range that yields optimal results.Profile: Although dasatinib is still in the early stages of development, the potential impact of this molecule on the treatment of CML could be revolutionary, not only providing a much needed treatment option for patients with imatinib-resistant CML, but also, combined with imatinib, could possibly prove useful in delaying the onset of resistance to treatment. Furthermore, combined with other agents active in CML, dasatinib could have potential utility in purging residual leukemic cells in patients whose disease is controlled by

  18. Adherence to Monitoring Tests in Patients With Chronic Myeloid Leukemia in Lebanon.

    Science.gov (United States)

    Massoud, Marcel; Nasr, Fadi; Sakr, Riwa; Hawi, Jenny; Kerbage, Fouad; Chahine, Georges

    2016-08-01

    The present study was performed to determine whether the adherence to regular follow-up assessments using standardized real-time quantitative polymerase chain reaction (qPCR) and/or cytogenetic tests in Lebanese patients with chronic myeloid leukemia (CML) meet the European LeukemiaNet recommendations. The present study was a retrospective analysis of 34 patients diagnosed with chronic phase CML who had been treated with tyrosine kinase inhibitors and monitored with regular cytogenetic tests and/or measurement of the BCR-ABL transcript level at 3, 6, and 12 months from 2006 until 2015 in 3 university hospitals in Lebanon. All patients were included and monitored in an adherence program (SAWA program). The male/female ratio was 3:1. The median age was 50 years, and the mean age was 50 years. As frontline treatment, 29 patients started imatinib and 5 patients received second-generation tyrosine kinase inhibitors. We defined compliance to the monitoring tests as regulary realizing the qPCR at 3, 6, and 12 months. Of the 36 patients, 15 underwent the recommended tests at 3, 6, and 12 months, representing a compliance rate of 41.6%; 28 of the 34 patients underwent the recommended tests only twice in the first follow-up year. Only 14 patients underwent qPCR at 3 months. We believe that despite the inclusion of our patients in an adherence program, the compliance rate is still low. We also believe that greater effort is required to improve the adherence to regular follow-up examinations. PMID:27220473

  19. Isolated central nervous system relapse of chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation

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    Fuchs Mary

    2012-08-01

    Full Text Available Abstract Background This case report highlights the relevance of quantifying the BCR-ABL gene in cerebrospinal fluid of patients with suspected relapse of chronic myeloid leukemia in the central nervous system. Case presentation We report on a female patient with isolated central nervous system relapse of chronic myeloid leukemia (CML during peripheral remission after allogeneic hematopoietic stem cell transplantation. The patient showed a progressive cognitive decline as the main symptom. MRI revealed a hydrocephalus and an increase in cell count in the cerebrospinal fluid (CSF with around 50% immature blasts in the differential count. A highly elevated BCR-ABL/ ABL ratio was detected in the CSF, whilst the ratio for peripheral blood and bone marrow was not altered. On treatment of the malresorptive hydrocephalus with shunt surgery, the patient showed an initial cognitive improvement, followed by a secondary deterioration. At this time, the cranial MRI showed leukemic infiltration of lateral ventricles walls. Hence, intrathecal administration of cytarabine, methotrexate, and dexamethasone was initiated, which caused a significant decrease of cells in the CSF. Soon after, the patient demonstrated significant cognitive improvement with a good participation in daily activities. At a later time point, after the patient had lost the major molecular response of CML, therapy with dasatinib was initiated. In a further follow-up, the patient was neurologically and hematologically stable. Conclusions In patients with treated CML, the rare case of an isolated CNS blast crisis has to be taken into account if neurological symptoms evolve. The analysis of BCR-ABL in the CSF is a further option for the reliable detection of primary isolated relapse of CML in these patients.

  20. A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia

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    Tucker DL

    2015-06-01

    Full Text Available David L Tucker, Simon A Rule Department of Haematology, Plymouth Hospitals NHS Trust, Plymouth, UK Abstract: Although chemo-immunotherapy remains at the forefront of first-line treatment for mantle cell lymphoma (MCL and chronic lymphocytic leukemia (CLL, small molecules, such as ibrutinib, are beginning to play a significant role, particularly in patients with multiply relapsed or chemotherapy-refractory disease and where toxicity is an overriding concern. Ibrutinib is a first-in-class, oral inhibitor of Bruton’s tyrosine kinase, which functions by irreversible inhibition of the downstream signaling pathway of the B-cell receptor, which normally promotes cell survival and proliferation. Early clinical trials have demonstrated excellent tolerability and a modest side-effect profile even in elderly and multiply pretreated patient cohorts. Although the majority of disease responses tend to be partial, efficacy data have also been encouraging with more than two-thirds of patients with CLL and MCL demonstrating a durable response, even in the high-risk disease setting. Resistance mechanisms are only partially understood and appear to be multifactorial, including the binding site mutation C481S, and escape through other common cell-signaling pathways. This article appraises the currently available data on safety and efficacy from clinical trials of ibrutinib in the management of MCL and CLL, both as a single agent and in combination with other therapies, and considers how this drug is likely to be used in future clinical practice. Keywords: ibrutinib, mantle cell lymphoma, chronic lymphocytic leukemia, Bruton’s tyrosine kinase, lymphoproliferative disorders

  1. Myc induced miR-144/451 contributes to the acquired imatinib resistance in chronic myelogenous leukemia cell K562

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    Liu, Li, E-mail: liuli029@yahoo.cn [Department of Hematology, Tangdu Hospital, The Fourth Military Medical University, Xi' an 710038 (China); Wang, Sitao; Chen, Renan; Wu, Yanlan; Zhang, Bei; Huang, Siyong; Zhang, Jingyi; Xiao, Fang; Wang, Meng; Liang, Yingmin [Department of Hematology, Tangdu Hospital, The Fourth Military Medical University, Xi' an 710038 (China)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Increased c-myc expression in imatinib resistant CML cells. Black-Right-Pointing-Pointer c-myc contributes the imatinib resistance in CML cells. Black-Right-Pointing-Pointer c-myc transcriptionally reduces the expression of miR-144/451 in K562R cells. Black-Right-Pointing-Pointer Restoration of miR-144/451 reverses the resistance of K562R cells to imatinib. -- Abstract: Imatinib resistance remains the big hurdle for CML therapy. Previous study reveals that c-myc is important for bcr-abl CML cell proliferation, while its role in imatinib resistance is largely unknown. In this study, we first found that c-myc expression is upregulated in imatinib resistant K562R cells, which in turn enhances the expression of miR-144/451. Knockdown of c-myc or restoration of miR-144/451 in the K562R cells sensitizes K562R cells to imatinib therapy. Our study here reveals an regulatory pathway between myc and miR-144/451 and highlights that targeting either myc or miR-144/451 might be valuable for eliminating the imatinib resistant CML cells.

  2. Myc induced miR-144/451 contributes to the acquired imatinib resistance in chronic myelogenous leukemia cell K562

    International Nuclear Information System (INIS)

    Highlights: ► Increased c-myc expression in imatinib resistant CML cells. ► c-myc contributes the imatinib resistance in CML cells. ► c-myc transcriptionally reduces the expression of miR-144/451 in K562R cells. ► Restoration of miR-144/451 reverses the resistance of K562R cells to imatinib. -- Abstract: Imatinib resistance remains the big hurdle for CML therapy. Previous study reveals that c-myc is important for bcr–abl CML cell proliferation, while its role in imatinib resistance is largely unknown. In this study, we first found that c-myc expression is upregulated in imatinib resistant K562R cells, which in turn enhances the expression of miR-144/451. Knockdown of c-myc or restoration of miR-144/451 in the K562R cells sensitizes K562R cells to imatinib therapy. Our study here reveals an regulatory pathway between myc and miR-144/451 and highlights that targeting either myc or miR-144/451 might be valuable for eliminating the imatinib resistant CML cells.

  3. Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation

    Science.gov (United States)

    2016-05-03

    Acute Lymphoblastic Leukemia (ALL); Acute Myeloid Leukemia (AML); Myeloid Sarcoma; Chronic Myelogenous Leukemia (CML); Juvenile Myelomonocytic Leukemia (JMML); Myelodysplastic Syndrome (MDS); Non-Hodgkin Lymphoma (NHL)

  4. Treating refractory leukemias in childhood, role of clofarabine

    OpenAIRE

    Harned, Theresa M.; Gaynon, Paul S.

    2008-01-01

    Approximately 4000 children and adolescents under the age of 20 years develop acute leukemia per year in the US. Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Despite impressive improvements in outcome, relapsed ALL is the fourth most common pediatric malignancy. Therapy for relapsed ALL remains unsatisfactory, and the majority of relapse patients still succumb to leukemia. Between one-third and one-half of patients with acute myelogenous leukemia (AML) relapse, and ...

  5. A phase I trial of the aurora kinase inhibitor, ENMD-2076, in patients with relapsed or refractory acute myeloid leukemia or chronic myelomonocytic leukemia.

    Science.gov (United States)

    Yee, Karen W L; Chen, Hsiao-Wei T; Hedley, David W; Chow, Sue; Brandwein, Joseph; Schuh, Andre C; Schimmer, Aaron D; Gupta, Vikas; Sanfelice, Deborah; Johnson, Tara; Le, Lisa W; Arnott, Jamie; Bray, Mark R; Sidor, Carolyn; Minden, Mark D

    2016-10-01

    ENMD-2076 is a novel, orally-active molecule that inhibits Aurora A kinase, as well as c-Kit, FLT3 and VEGFR2. A phase I study was conducted to determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D) and toxicities of ENMD-2076 in patients with acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML). Patients received escalating doses of ENMD-2076 administered orally daily [225 mg (n = 7), 375 mg (n = 6), 325 mg (n = 9), or 275 mg (n = 5)]. Twenty-seven patients were treated (26 AML; 1 CMML-2). The most common non-hematological toxicities of any grade, regardless of association with drug, were fatigue, diarrhea, dysphonia, dyspnea, hypertension, constipation, and abdominal pain. Dose-limiting toxicities (DLTs) consisted of grade 3 fatigue, grade 3 typhilitis, grade 3 syncope and grade 3 QTc prolongation). Of the 16 evaluable patients, one patient achieved a complete remission with incomplete count recovery (CRi), three experienced a morphologic leukemia-free state (MLFS) with a major hematologic improvement in platelets (HI-P), and 5 other patients had a reduction in marrow blast percentage (i.e. 11-65 %). The RP2D in this patient population is 225 mg orally once daily. PMID:27406088

  6. Expression and significance of Wnt5a gene and NPM1 gene in chronic myeloid leukemia patients

    Institute of Scientific and Technical Information of China (English)

    Liang-Tuo Wang; Xiang-Lan Zhang; Jian-Yu Situ; Yuan-Ying Huang

    2015-01-01

    Objective:To detect Wnt5a gene expression and NPM1 gene in chronic myeloid leukemia bone marrow cells and to explore its relevance and significance.Methods:Sixty cases of chronic myeloid leukemia patients in our hospital were included in the experimental group, taking up 20 cases in the blastic phase, 20 cases in the accelerated phase, and 20 cases in the chronic phase; and 60 cases with benign hematologic disease were included in the control group. Cultured bone marrow cells were detected by RT-PCR methods to analyze the significance of Wnt5a and NPM1 gene expressions.Results:Wnt5a mRNA in the three sub-groups of the experimental group had low semi-quantitative mean values and positive rates compared with the control group. NPM1 mRNA positive rates and median expression levels were higher, and the difference was statistically significant. In the three subgroups of the experimental group, Wnt5a mRNA semi-quantitative mean values and positive rates in the blastic phase and accelerated phase were low, while NPM1 mRNA positive rates and median expression levels were higher; and the difference was statistically significant. Wnt5a and NPM1 expression levels in patients' white blood cell count were associated with bone marrow blast cells; and the difference was statistically significant. However, this was not associated with age, hemoglobin content and platelet count; and the difference was not statistically significant.Conclusion: There is a certain degree of correlation between Wnt5a and NPM1 genes and the occurrence and development of chronic myeloid leukemia. Wnt5a gene may inhibit its occurrence, while NPM1 gene positivity promotes its progression, which may be applied in the diagnosis and treatment of chronic myeloid leukemia, providing a new way of analyzing prognosis and a theoretical basis for clinical application.

  7. Nilotinib: optimal therapy for patients with chronic myeloid leukemia and resistance or intolerance to imatinib

    Directory of Open Access Journals (Sweden)

    Ronan Swords

    2009-03-01

    Full Text Available Ronan Swords, Devalingam Mahalingam, Swaminathan Padmanabhan, Jennifer Carew, Francis GilesInstitute for Drug Development, Cancer Therapy and Research Centre, University of Texas Health Science Centre at San Antonio, USAAbstract: Chronic myeloid leukemia (CML is the consequence of a single balanced translocation that produces the BCR-ABL fusion oncogene which is detectable in over 90% of patients at presentation. The BCR-ABL inhibitor imatinib mesylate (IM has improved survival in all phases of CML and is the standard of care for newly diagnosed patients in chronic phase. Despite the very significant therapeutic benefits of IM, a small minority of patients with early stage disease do not benefit optimally while IM therapy in patients with advanced disease is of modest benefit in many. Diverse mechanisms may be responsible for IM failures, with point mutations within the Bcr-Abl kinase domain being amongst the most common resistance mechanisms described in patients with advanced CML. The development of novel agents designed to overcome IM resistance, while still primarily targeted on BCR-ABL, led to the creation of the high affinity aminopyrimidine inhibitor, nilotinib. Nilotinib is much more potent as a BCR-ABL inhibitor than IM and inhibits both wild type and IM-resistant BCR-ABL with significant clinical activity across the entire spectrum of BCR-ABL mutants with the exception of T315I. The selection of a second generation tyrosine kinase inhibitor to rescue patients with imatinib failure will be based on several factors including age, co-morbid medical problems and ABL kinase mutational profile. It should be noted that while the use of targeted BCR-ABL kinase inhibitors in CML represents a paradigm shift in CML management these agents are not likely to have activity against the quiescent CML stem cell pool. The purpose of this review is to summarize the pre-clinical and clinical data on nilotinib in patients with CML who have failed prior

  8. Planned Pregnancy in a Chronic Myeloid Leukemia Patient in Molecular Remission

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    Carolina Pavlovsky

    2012-01-01

    Full Text Available Excellent response rates and a good quality of life have been observed since the introduction of tyrosine kinase inhibitors (TKIs in chronic myeloid leukemia (CML treatment. Consequently, some challenges began to appear in CML women in child-bearing age wishing to become pregnant. Currently, many women around the world are in stable major/complete molecular response MMR/CMR (MMR: <0.1% BCR-ABL/ABL and CMR: undetectable BCR-ABL mRNA by RQ-PCR transcript levels on the international scale. The condition of stable MMR/CMR is linked to a long-term virtual absence of progression to the accelerated and blastic phase and to the possibility of stopping the TKI treatment with the maintenance of a condition of CMR in a proportion of cases. Imatinib teratogenic and prescribing information prohibits the use of it during pregnancy. We describe the case of a 36-year-old female patient with CML in chronic phase who stopped imatinib after 2 years in major molecular response (MMR to plan a pregnancy. Molecular monitoring by RQ-PCR was performed quarterly. She achieved a safe pregnancy and delivery maintaining an optimal molecular response throughout the pregnancy. Isolated literature reports have been described, but no formal advice has been described at present time.

  9. Novel Approaches for Graft-versus-Host Disease Prevention Compared to Contemporary Controls (BMT CTN 1203)

    Science.gov (United States)

    2016-06-16

    Acute Leukemia; Chronic Myelogenous Leukemia; Myelodysplasia; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoma, B-Cell; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Hodgkin's Lymphoma

  10. Using gene co-expression network analysis to predict biomarkers for chronic lymphocytic leukemia

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    Borlawsky Tara B

    2010-10-01

    Full Text Available Abstract Background Chronic lymphocytic leukemia (CLL is the most common adult leukemia. It is a highly heterogeneous disease, and can be divided roughly into indolent and progressive stages based on classic clinical markers. Immunoglobin heavy chain variable region (IgVH mutational status was found to be associated with patient survival outcome, and biomarkers linked to the IgVH status has been a focus in the CLL prognosis research field. However, biomarkers highly correlated with IgVH mutational status which can accurately predict the survival outcome are yet to be discovered. Results In this paper, we investigate the use of gene co-expression network analysis to identify potential biomarkers for CLL. Specifically we focused on the co-expression network involving ZAP70, a well characterized biomarker for CLL. We selected 23 microarray datasets corresponding to multiple types of cancer from the Gene Expression Omnibus (GEO and used the frequent network mining algorithm CODENSE to identify highly connected gene co-expression networks spanning the entire genome, then evaluated the genes in the co-expression network in which ZAP70 is involved. We then applied a set of feature selection methods to further select genes which are capable of predicting IgVH mutation status from the ZAP70 co-expression network. Conclusions We have identified a set of genes that are potential CLL prognostic biomarkers IL2RB, CD8A, CD247, LAG3 and KLRK1, which can predict CLL patient IgVH mutational status with high accuracies. Their prognostic capabilities were cross-validated by applying these biomarker candidates to classify patients into different outcome groups using a CLL microarray datasets with clinical information.

  11. Hypoxia selects bortezomib-resistant stem cells of chronic myeloid leukemia.

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    Michele Tanturli

    Full Text Available We previously demonstrated that severe hypoxia inhibits growth of Chronic Myeloid Leukemia (CML cells and selects stem cells where BCR/Abl(protein is suppressed, although mRNA is not, so that hypoxia-selected stem cells, while remaining leukemic, are independent of BCR/Abl signaling and thereby refractory to Imatinib-mesylate. The main target of this study was to address the effects of the proteasome inhibitor Bortezomib (BZ on the maintenance of stem or progenitor cells in hypoxic primary cultures (LC1, by determining the capacity of LC1 cells to repopulate normoxic secondary cultures (LC2 and the kinetics of this repopulation. Unselected K562 cells from day-2 hypoxic LC1 repopulated LC2 with rapid, progenitor-type kinetics; this repopulation was suppressed by BZ addition to LC1 at time 0, but completely resistant to day-1 BZ, indicating that progenitors require some time to adapt to stand hypoxia. K562 cells selected in hypoxic day-7 LC1 repopulated LC2 with stem-type kinetics, which was largely resistant to BZ added at either time 0 or day 1, indicating that hypoxia-selectable stem cells are BZ-resistant per se, i.e. before their selection. Furthermore, these cells were completely resistant to day-6 BZ, i.e. after selection. On the other hand, hypoxia-selected stem cells from CD34-positive cells of blast-crisis CML patients appeared completely resistant to either time-0 or day-1 BZ. To exploit in vitro the capacity of CML cells to adapt to hypoxia enabled to detect a subset of BZ-resistant leukemia stem cells, a finding of particular relevance in light of the fact that our experimental system mimics the physiologically hypoxic environment of bone marrow niches where leukemia stem cells most likely home and sustain minimal residual disease in vivo. This suggests the use of BZ as an enhanced strategy to control CML. in particular to prevent relapse of disease, to be considered with caution and to need further deepening.

  12. Nilotinib treatment in mouse models of P190 Bcr/Abl lymphoblastic leukemia

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    Groffen John

    2007-10-01

    Full Text Available Abstract Background Ph-positive leukemias are caused by the aberrant fusion of the BCR and ABL genes. Nilotinib is a selective Bcr/Abl tyrosine kinase inhibitor related to imatinib, which is widely used to treat chronic myelogenous leukemia. Because Ph-positive acute lymphoblastic leukemia only responds transiently to imatinib therapy, we have used mouse models to test the efficacy of nilotinib against lymphoblastic leukemia caused by the P190 form of Bcr/Abl. Results After transplant of 10,000 highly malignant leukemic cells into compatible recipients, untreated mice succumbed to leukemia within 21 days, whereas mice treated with 75 mg/kg nilotinib survived significantly longer. We examined cells from mice that developed leukemia while under treatment for Bcr/Abl kinase domain point mutations but these were not detected. In addition, culture of such cells ex vivo showed that they were as sensitive as the parental cell line to nilotinib but that the presence of stromal support allowed resistant cells to grow out. Nilotinib also exhibited impressive anti-leukemia activity in P190 Bcr/Abl transgenic mice that had developed overt leukemia/lymphoma masses and that otherwise would have been expected to die within 7 days. Visible lymphoma masses disappeared within six days of treatment and leukemic cell numbers in peripheral blood were significantly reduced. Treated mice survived more than 30 days. Conclusion These results show that nilotinib has very impressive anti-leukemia activity but that lymphoblastic leukemia cells can become unresponsive to it both in vitro and in vivo through mechanisms that appear to be Bcr/Abl independent.

  13. Leukemia, an effective model for chemical biology and target therapy1

    Institute of Scientific and Technical Information of China (English)

    Guo-qiang CHEN; Li-shun WANG; Ying-li WU; Yun YU

    2007-01-01

    The rapid rise of chemical biology aimed at studying signaling networks for basic cellular activities using specific, active small molecules as probes has greatly accelerated research on pathological mechanisms and target therapy of diseases.This research is especially important for malignant tumors such as leukemia, a heterogeneous group of hematopoietic malignancies that occurs worldwide. With the use of a chemical approach combined with genetic manipulation, great progresshas been achieved over the past few decades on the biological, molecular and cytogenetic aspects of leukemia, and in its diagnosis and therapy. In particular,discoveries of the clinical effectiveness of all-trans rctinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia and the kinase inhibitorsImatinib and Dasatinib in the treatment of chronic myelogenous leukemia not only make target therapy of leukemia a reality, but also push mechanisms of leukemo-genesis and leukemic cell activities forward. This review will outline advances in chemical biology that help our understanding of the molecular mechanisms of cell differentiation and apoptosis induction and target therapy of leukemia.

  14. Reversible Renal Insufficiency Secondary to Extrinsic Splenic Compression of the Kidney in a Patient with Chronic Lymphocytic Leukemia

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    Miriam Hadj-Moussa

    2010-01-01

    Full Text Available While increased renal venous and direct renal parenchymal pressure may cause renal insufficiency, there are no prior reports of hypersplenism secondary to chronic lymphocytic leukemia (CLL doing so. This first report of massive splenomegaly leading to marked compression of the left kidney associated with renal insufficiency that resolved after splenectomy illustrates that profound extrinsic renal compression from splenomegaly may significantly compromise left renal function and splenectomy should be considered in this situation.

  15. Total-body irradiation with 25-MV photons in advanced non-Hodgkin's lymphoma and chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma were treated with total-body irradiation (TBI). One group was treated after chemotherapy failed, while the other group received TBI initially. TBI was ineffective against CLL after chemotherapy failed. All patients with lymphocytic lymphoma who initially responded to chemotherapy but later relapsed were helped by TBI, as were 88 percent of patients with previously untreated lymphocytic lymphomas

  16. Evaluation of 13q14 Status in Patients with Chronic Lymphocytic Leukemia Using Single Nucleotide Polymorphism-Based Techniques

    OpenAIRE

    Hanlon, Katy; Ellard, Sian; Rudin, Claudius E.; Thorne, Susan; Davies, Teresa; Harries, Lorna W.

    2009-01-01

    Deletions of chromosome 13q14 are common in chronic lymphocytic leukemia and other cancers, demonstrating the importance of this region in tumorigenesis. We report the use of two single-nucleotide polymorphism (SNP)-based techniques to determine 13q loss of heterozygosity (LOH) status in 15 patients with CLL: (i) digital SNP (dSNP), where analysis of heterozygous SNPs detects allelic imbalances, and (ii) DNA sequencing, where LOH is identified by comparison of allelic peak heights in normal a...

  17. A clinical and laboratory study of chronic myeloid leukemia with atypical BCR-ABL fusion gene subtypes

    Institute of Scientific and Technical Information of China (English)

    桂晓敏

    2014-01-01

    Objective To explore the clinical and laboratory features of chronic myeloid leukemia(CML)with atypical e14a3 and e19a2 BCR-ABL fusion gene subtypes.Methods We retrospectively analyzed a cohort of CML patients with Ph chromosome positive confirmed by cytogenetic and FISH but classical e13a3(b2a2),e14a2(b3a2)and e1a2 fusion transcripts negative identified by

  18. Effect of up-regulated expression of tumor suppressor gene p14ARF on apoptosis of chronic myeloid leukemia cells

    Institute of Scientific and Technical Information of China (English)

    白元松

    2013-01-01

    Objective To investigate the effect of up-regulated expression of tumor suppressor gene p14ARFon apoptosis of chronic myeloid leukemia (CML) cells and its interaction with imatinib.Methods Tumor suppressor gene p14ARFwas transduced into K562 (K562-p14ARF) and 4blast crisis primary CML cells (CML-BC 1-4) using vesicular stomatitis virus glycoprotein (VSV-G)

  19. Pleural effusion as the initial manifestation of chronic myeloid leukemia: Report of a case with clinical and cytologic correlation

    Directory of Open Access Journals (Sweden)

    Paras Nuwal

    2012-01-01

    Full Text Available Pleural effusion in patients with chronic myeloid leukemia (CML is very rare and poorly understood. We report here a 26-year-old male patient having CML and presenting with pleural effusion as the first clinical sign. The possible mechanism of pleural effusion in CML, the cytological interpretive problem and the clinical significance of finding immature leucocytes in pleural fluid are also briefly discussed.

  20. DNA repair initiated in chronic lymphocytic leukemia lymphocytes by 4-hydroperoxycyclophosphamide is inhibited by fludarabine and clofarabine.

    OpenAIRE

    Yamauchi, Takahiro; Nowak, Billie J.; Michael J Keating; Plunkett, William

    2001-01-01

    PURPOSE: Chronic lymphocytic leukemia (CLL) lymphocytes respond to DNA alkylation by excision repair, with the extent of repair increasing as the cells acquire resistance to alkylating agents. Because incorporation of nucleotide analogues into the repair patches elicits death signals in quiescent cells, the increased capacity for excision repair in alkylator-resistant cells could facilitate incorporation of nucleotide analogues. We hypothesized that the mechanism-based interaction of nucleosi...

  1. BCR Signaling Inhibitors: an Overview of Toxicities Associated with Ibrutinib and Idelalisib in Patients with Chronic Lymphocytic Leukemia

    OpenAIRE

    Falchi, Lorenzo; Baron, Jessica M.; Orlikowski, Carrie Anne; Ferrajoli, Alessandra

    2016-01-01

    The B-cell receptor (BCR) signaling inhibitors ibrutinib and idelalisib are revolutionizing the treatment of chronic lymphocytic leukemia (CLL) and other B-cell malignancies. These oral agents, both alone and in combination with other drugs, have shown remarkable clinical activity in relapsed or refractory CLL across all risk groups, and have been approved by the Food and Drug Administration for this indication. Preliminary data suggest that an even greater benefit can be expected in treatmen...

  2. Ibrutinib: A New Frontier in the Treatment of Chronic Lymphocytic Leukemia by Bruton’s Tyrosine Kinase Inhibition

    OpenAIRE

    Dias, Ajoy Lawrence; Jain, Dharamvir

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is characterized by progressive accumulation of nonfunctional mature B cells in blood, bone marrow and lymphoid tissues. In the last decade, our understanding of CLL and consequently our diagnostic and therapeutic approaches have changed dramatically. Conventional fludarabine based chemotherapy has led to improved disease response and longer survival in young patients with CLL. However its application in elderly patients has been restricted by substantial my...

  3. BCR SIGNALING INHIBITORS: AN OVERVIEW OF TOXICITIES ASSOCIATED WITH IBRUTINIB AND IDELALISIB IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA

    OpenAIRE

    Lorenzo Falchi; Baron, Jessica M.; Carrie Anne Orlikowski; Alessandra Ferrajoli

    2016-01-01

    The B-cell receptor signaling inhibitors ibrutinib and idelalisib are revolutionizing the treatment landscape of chronic lymphocytic leukemia (CLL) and other B-cell malignancies. These oral agents, both alone and in combination with other drugs, have shown remarkable clinical activity in relapsed or refractory CLL across all risk groups, and have been approved by the Food and Drug Administration for this indication. Preliminary data suggest that an even greater benefit can be expected in trea...

  4. Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study

    OpenAIRE

    Herman, Sarah E. M.; Niemann, Carsten U.; Farooqui, Mohammed; Jones, Jade; Mustafa, Rashida Z.; Lipsky, Andrew; Saba, Nakhle; Martyr, Sabrina; Soto, Susan; Valdez, Janet; Gyamfi, Jennifer A.; Maric, Irina; Calvo, Katherine R.; Pedersen, Lone B; Geisler, Christian H.

    2014-01-01

    Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further investigation. We here report correlative studies in 64 patients with CLL treated with ibrutinib. We quantified tumor burden in blood, lymph nodes, spleen, and bone marrow, assessed phenotypic change...

  5. The splicing modulator sudemycin induces a specific antitumor response and cooperates with ibrutinib in chronic lymphocytic leukemia

    OpenAIRE

    Xargay-Torrent, Sçilvia; López Guerra, Mónica; Rosich, Laia; Montraveta, Arnau; Roldán, Jocabed; Rodríguez, Vanina; Villamor Casas, Neus; Aymerich, Marta; Lagisetti, Chandraiah; Webb, Thomas R.; López Otín, Carlos; Campo, Elías; Colomer, Dolors

    2015-01-01

    Mutations or deregulated expression of the components of the spliceosome can influence the splicing pattern of several genes and contribute to the development of tumors. In this context, we report that the spliceosome modulator sudemycin induces selective cytotoxicity in primary chronic lymphocytic leukemia (CLL) cells when compared with healthy lymphocytes and tumor cells from other B-lymphoid malignancies, with a slight bias for CLL cases with mutations in spliceosome-RNA processing machine...

  6. Ibrutinib: an evidence-based review of its potential in the treatment of advanced chronic lymphocytic leukemia

    OpenAIRE

    Chavez JC; Sahakian E; Pinilla-Ibarz J

    2013-01-01

    Julio C Chavez, Eva Sahakian, Javier Pinilla-IbarzH Lee Moffitt Cancer and Research Institute, Division of Malignant Hematology, and University of South Florida, Tampa, FL, USAAbstract: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a variable course, and remains an incurable disease. Frequent relapses and eventual resistance to fludarabine characterize symptomatic CLL and portends a dismal prognosis for patients. Growing evidence has shown that signaling pathways such as ...

  7. Sweet Syndrome in a Patient with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Curious Lymphocyte/Neutrophil Fluctuations

    OpenAIRE

    Çiğdem Usul Afşar; Semra Paydaş; Meral Günaldı; Berna Bozkurt Duman; Vehbi Erçolak; Suzan Zorludemir; Arbil Açıkalın

    2013-01-01

    Sweet syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by tender, red inflammatory nodules or papules that occur in association with infection, malignancy, connective tissue disease, or following exposure to certain drugs. Here, we present Sweet syndrome in a case with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) which is a relatively rare co-occurrence. Conflict of interest:None declared.

  8. Sweet Syndrome in a Patient with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Curious Lymphocyte/Neutrophil Fluctuations

    Directory of Open Access Journals (Sweden)

    Çiğdem Usul Afşar

    2013-12-01

    Full Text Available Sweet syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by tender, red inflammatory nodules or papules that occur in association with infection, malignancy, connective tissue disease, or following exposure to certain drugs. Here, we present Sweet syndrome in a case with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL which is a relatively rare co-occurrence.

  9. White blood cells of peripheral blood with ConA-positive glycotopes in patients with chronic leukemia

    Directory of Open Access Journals (Sweden)

    G. S. Maslak

    2015-09-01

     Tumor growth progression of blood cells occurs due to changes in their genetic apparatus, which affects not only the cells morphological characteristics, but also their functional activity which to a greater extent depends on the membrane surface structures, a significant part of which is of glycoprotein nature. Complex type N-glycans are components of surface glycoproteins in the most of leukocytes. Thus, the study of changes in carbohydrate determinants of glycoproteins on the surface of leucocytes in tumorigenesis can help to reveal the mechanisms of this process. The aim of our study was to investigate the monocytes and granulocytes cytoplasmic membrane N-glycosylation in patients with chronic leukemia. The object of the study were blood cells of patients with chronic lymphocytic leukemia (n = 12 and polycythemia vera (n = 15 aged 58–66 years. Healthy hematologic volunteers (n = 15 aged 55 to 65 years were in the control group. N-glycan exposure on monocytes and granulocytes was investigated by flow cytometer Beckman Сoulter EPICS with Canavalia ensiformis lectin – Con A conjugated with fluorescent labels. The number of dead cells was monitored by means of binding them with propidium iodide. The result has been analyzed with FC Express. According to our data, levels of ConA-positive monocytes and granulocytes were 9,9 ± 1,0% and 32,7 ± 3,2%, respectively, in peripheral blood of healthy persons. The level of ConA-positive monocytes decreased to 31,0 ± 2,3% and the number of ConA-binding granulocytes increased to 66,7 ± 3,8% in patients with chronic lymphocytic leukemia compared with the norm. The number of ConA-positive monocytes decreased 3.3 times, and the level of granulocytes interacting with Canavalia ensiformis lectin slightly increased relative to control in polycythemia vera patients. There is significant increase in Con A-positive epitopes on granulocytes in patients with chronic lymphocytic leukemia and polycythemia vera compared with the

  10. Igs Expressed by Chronic Lymphocytic Leukemia B Cells Show Limited Binding-Site Structure Variability

    KAUST Repository

    Marcatili, P.

    2013-05-01

    Ag selection has been suggested to play a role in chronic lymphocytic leukemia (CLL) pathogenesis, but no large-scale analysis has been performed so far on the structure of the Ag-binding sites (ABSs) of leukemic cell Igs. We sequenced both H and L chain V(D)J rearrangements from 366 CLL patients and modeled their three-dimensional structures. The resulting ABS structures were clustered into a small number of discrete sets, each containing ABSs with similar shapes and physicochemical properties. This structural classification correlates well with other known prognostic factors such as Ig mutation status and recurrent (stereotyped) receptors, but it shows a better prognostic value, at least in the case of one structural cluster for which clinical data were available. These findings suggest, for the first time, to our knowledge, on the basis of a structural analysis of the Ab-binding sites, that selection by a finite quota of antigenic structures operates on most CLL cases, whether mutated or unmutated. Copyright © 2013 by The American Association of Immunologists, Inc.

  11. Automatic detection of axillary lymphadenopathy on CT scans of untreated chronic lymphocytic leukemia patients

    Science.gov (United States)

    Liu, Jiamin; Hua, Jeremy; Chellappa, Vivek; Petrick, Nicholas; Sahiner, Berkman; Farooqui, Mohammed; Marti, Gerald; Wiestner, Adrian; Summers, Ronald M.

    2012-03-01

    Patients with chronic lymphocytic leukemia (CLL) have an increased frequency of axillary lymphadenopathy. Pretreatment CT scans can be used to upstage patients at the time of presentation and post-treatment CT scans can reduce the number of complete responses. In the current clinical workflow, the detection and diagnosis of lymph nodes is usually performed manually by examining all slices of CT images, which can be time consuming and highly dependent on the observer's experience. A system for automatic lymph node detection and measurement is desired. We propose a computer aided detection (CAD) system for axillary lymph nodes on CT scans in CLL patients. The lung is first automatically segmented and the patient's body in lung region is extracted to set the search region for lymph nodes. Multi-scale Hessian based blob detection is then applied to detect potential lymph nodes within the search region. Next, the detected potential candidates are segmented by fast level set method. Finally, features are calculated from the segmented candidates and support vector machine (SVM) classification is utilized for false positive reduction. Two blobness features, Frangi's and Li's, are tested and their free-response receiver operating characteristic (FROC) curves are generated to assess system performance. We applied our detection system to 12 patients with 168 axillary lymph nodes measuring greater than 10 mm. All lymph nodes are manually labeled as ground truth. The system achieved sensitivities of 81% and 85% at 2 false positives per patient for Frangi's and Li's blobness, respectively.

  12. Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations.

    Science.gov (United States)

    Baliakas, Panagiotis; Agathangelidis, Andreas; Hadzidimitriou, Anastasia; Sutton, Lesley-Ann; Minga, Eva; Tsanousa, Athina; Scarfò, Lydia; Davis, Zadie; Yan, Xiao-Jie; Shanafelt, Tait; Plevova, Karla; Sandberg, Yorick; Vojdeman, Fie Juhl; Boudjogra, Myriam; Tzenou, Tatiana; Chatzouli, Maria; Chu, Charles C; Veronese, Silvio; Gardiner, Anne; Mansouri, Larry; Smedby, Karin E; Pedersen, Lone Bredo; Moreno, Denis; Van Lom, Kirsten; Giudicelli, Véronique; Francova, Hana Skuhrova; Nguyen-Khac, Florence; Panagiotidis, Panagiotis; Juliusson, Gunnar; Angelis, Lefteris; Anagnostopoulos, Achilles; Lefranc, Marie-Paule; Facco, Monica; Trentin, Livio; Catherwood, Mark; Montillo, Marco; Geisler, Christian H; Langerak, Anton W; Pospisilova, Sarka; Chiorazzi, Nicholas; Oscier, David; Jelinek, Diane F; Darzentas, Nikos; Belessi, Chrysoula; Davi, Frederic; Ghia, Paolo; Rosenquist, Richard; Stamatopoulos, Kostas

    2015-01-29

    An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.

  13. Intermittent targeted therapies and stochastic evolution in patients affected by chronic myeloid leukemia

    Science.gov (United States)

    Pizzolato, N.; Persano Adorno, D.; Valenti, D.; Spagnolo, B.

    2016-05-01

    Front line therapy for the treatment of patients affected by chronic myeloid leukemia (CML) is based on the administration of tyrosine kinase inhibitors, namely imatinib or, more recently, axitinib. Although imatinib is highly effective and represents an example of a successful molecular targeted therapy, the appearance of resistance is observed in a proportion of patients, especially those in advanced stages. In this work, we investigate the appearance of resistance in patients affected by CML, by modeling the evolutionary dynamics of cancerous cell populations in a simulated patient treated by an intermittent targeted therapy. We simulate, with the Monte Carlo method, the stochastic evolution of initially healthy cells to leukemic clones, due to genetic mutations and changes in their reproductive behavior. We first present the model and its validation with experimental data by considering a continuous therapy. Then, we investigate how fluctuations in the number of leukemic cells affect patient response to the therapy when the drug is administered with an intermittent time scheduling. Here we show that an intermittent therapy (IT) represents a valid choice in patients with high risk of toxicity, despite an associated delay to the complete restoration of healthy cells. Moreover, a suitably tuned IT can reduce the probability of developing resistance.

  14. Total expression of HLA-G and TLR-9 in chronic lymphocytic leukemia patients.

    Science.gov (United States)

    Własiuk, Paulina; Tomczak, Waldemar; Zając, Małgorzata; Dmoszyńska, Anna; Giannopoulos, Krzysztof

    2013-12-01

    Suppressed immune status facilitates immune escape mechanisms that allow chronic lymphocytic leukemia cells to proliferate and expand. The expression of HLA-G could effectively inhibit the immune response. In immune response inhibitory signals follow activation of immune system which might be occur during bacterial or viral infection in CLL patients. In the current study we characterized two components of immune system, inhibitory molecule HLA-G with its receptor - CD85j and Toll-like receptor 9. The material was obtained from 41 CLL patients and 41 HV with similar median age. In CLL patients expression of intracellular and surface HLA-G and soluble HLA-G levels were significantly higher than in HV. We found higher expression of CD85j compared to HV and the positive correlation between expression of HLA-G and CD85j. All the CLL cells expressed TLR-9, and the level of expression positively correlated with expression of HLA-G and CD85j. Patients with higher expression of intracellular expression of TLR-9 have significantly longer treatment-free survival than patients with low expression of TLR-9 (57 months vs. 8 months, respectively). Summarizing in CLL we characterized activatory and inhibitory components of immune system that might be connected functionally. Analysis of TLR-9 expression might have additional prognostic value for CLL patients.

  15. The VEGF receptor, neuropilin-1, represents a promising novel target for chronic lymphocytic leukemia patients.

    Science.gov (United States)

    Piechnik, Agnieszka; Dmoszynska, Anna; Omiotek, Marcin; Mlak, Radosław; Kowal, Małgorzata; Stilgenbauer, Stephan; Bullinger, Lars; Giannopoulos, Krzysztof

    2013-09-15

    Angiogenesis has been shown to substantially contribute to the progression of chronic lymphocytic leukemia (CLL). Neuropilin-1 (NRP1) represents a receptor for vascular endothelial growth factor (VEGF), which has been reported to be overexpressed in several malignancies. In our study, we characterized mRNA levels of VEGF receptors including NRP1 in a large cohort of CLL patients (n = 114), additionally we performed a detailed characterization of NRP1 expression on B cells, plasmacytoid dendritic cells (PDCs) and regulatory T cells (Tregs). The expression of NRP1 was significantly higher on leukemic lymphocytes compared to control B lymphocytes on mRNA and protein levels (22.72% vs. 0.2%, p = 0.0003, respectively), Tregs (42.6% vs. 16.05%, p = 0.0003) and PDCs (100% vs. 98% p < 0.0001). In functional studies, we found higher NRP1 expression on CLL cells after stimulation with VEGF. The correlation between expression of VEGF receptors: FLT1, NRP1 and FOXP3 expression (r(2) = 0.53, p < 0.0001 and r(2) = 0.49, p < 0.0001, respectively) was observed. Earlier we described the specific Treg reduction during the therapy with thalidomide in vivo. Now we observe the reduction of the NRP1 expression on Tregs in vitro, thereby suggesting a possible target of thalidomide action. In conclusion, NRP1 might represent an interesting link between angiogenesis and tolerance mechanisms and represents interesting target for therapy.

  16. The function of a novel immunophenotype candidate molecule PD-1 in chronic lymphocytic leukemia.

    Science.gov (United States)

    Grzywnowicz, Maciej; Karabon, Lidia; Karczmarczyk, Agnieszka; Zajac, Malgorzata; Skorka, Katarzyna; Zaleska, Joanna; Wlasiuk, Paulina; Chocholska, Sylwia; Tomczak, Waldemar; Bojarska-Junak, Agnieszka; Dmoszynska, Anna; Frydecka, Irena; Giannopoulos, Krzysztof

    2015-01-01

    Programmed death-1 (PD-1) is a negative receptor expressed on lymphocytes including malignant B cells in chronic lymphocytic leukemia (CLL). In this work, we found that patients with CLL had a higher expression of PD-1 transcript (PDCD1) than healthy volunteers (p < 0.0001). PDCD1 expression was comparable between CLL cells from accumulation (peripheral blood) and proliferation (bone marrow) disease compartments. In blood samples of patients with mutated IGHV genes PDCD1 expression was higher than with unmutated IGHV (p = 0.0299). We demonstrated that phosphorylation of SYK and LYN, key B-cell receptor signaling kinases, was independent of PD-1 expression in patients with CLL, while ZAP-70 phosphorylation in negative tyrosine residue 292 showed strong inverse correlation (r = - 0.8, p = 0.0019). No associations between five single nucleotide polymorphisms of PDCD1, their expressions and susceptibility to CLL were found. In conclusion, PD-1 might be an independent, universal marker of CLL cells and a part of their activated phenotype, and subsequently might modulate the function of ZAP-70.

  17. Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia.

    Science.gov (United States)

    Rawstron, Andy C; Kennedy, Ben; Moreton, Paul; Dickinson, Anita J; Cullen, Matthew J; Richards, Stephen J; Jack, Andrew S; Hillmen, Peter

    2004-03-15

    Alemtuzumab therapy is effective for some refractory chronic lymphocytic leukemia (CLL), but identifying responders requires at least 8 weeks of therapy. Early identification of nonresponders would minimize toxicity and/or facilitate more effective strategies. The aim of this study was to identify a minimally invasive method for early prediction of response and relapse. Flow cytometric monitoring was performed in 887 blood samples and 201 marrow samples from 43 patients undergoing intravenous alemtuzumab therapy. Although the absolute lymphocytosis was resolved in all patients by week 4, significant depletion of bone marrow tumor only occurred if circulating B-lymphocyte counts were persistently less than 0.001 x 10(9)/L, which was rare in nonresponders. The majority of patients (16/28) who did not benefit from a full course of therapy were identified with 100% positive predictive value using the following algorithm: peripheral B-cell count greater than 0.001 x 10(9)/L at week 2 with less than 1 log depletion of circulating B cells between weeks 2 and 4. Monitoring CLL levels after treatment identified patients at risk of early disease progression and could potentially improve patient management. During alemtuzumab therapy, bone marrow CLL depletion only occurs after abrogation of circulating tumor, requiring close monitoring of circulating B-cell levels. If validated in prospective studies, blood monitoring at 2 and 4 weeks may be used to optimize therapy.

  18. New developments in the management of chronic lymphocytic leukemia: role of ofatumumab

    Directory of Open Access Journals (Sweden)

    Laurenti L

    2016-01-01

    Full Text Available Luca Laurenti,1 Idanna Innocenti,1 Francesco Autore,1 Simona Sica,1 Dimitar G Efremov2 1Department of Hematology, Catholic University of the Sacred Heart, Rome, 2Molecular Hematology, International Centre for Genetic Engineering and Biotechnology, Monterotondo, Italy Abstract: Ofatumumab is one of the three anti-CD20 monoclonal antibodies currently available for the treatment of chronic lymphocytic leukemia (CLL. The US Food and Drug Administration (FDA approved the use of ofatumumab in patients with CLL refractory to fludarabine and alemtuzumab in 2009, and the European Medicines Agency (EMA granted approval for the same indication in 2010. Subsequent positive results of ofatumumab in combination with chlorambucil in treatment-naïve patients led the FDA in April 2014 to approve the use of this combination for first-line treatment of patients with CLL for whom fludarabine-based therapy is considered inappropriate. Later that year, the EMA approved the use of ofatumumab in combination with chlorambucil or bendamustine for the same indication. Ofatumumab has also shown potential as maintenance therapy for patients with relapsed CLL; an application to broaden the label for ofatumumab as maintenance therapy was submitted earlier this year to the EMA and FDA. Finally, ofatumumab has shown promising activity in combination with ibrutinib or idelalisib in relapsed/refractory CLL patients; combinations of ofatumumab with B-cell-receptor pathway inhibitors could represent another potential use of this antibody in the near future. Keywords: CLL, ofatumumab, monoclonal antibodies, immunotherapy

  19. Spred2 is involved in imatinib-induced cytotoxicity in chronic myeloid leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiao-Yun; Yang, Yue-Feng; Wu, Chu-Tse; Xiao, Feng-Jun; Zhang, Qun-Wei [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Ma, Xiao-Ni [Lanzhou University of Technology, Lanzhou 730050 (China); Li, Qing-Fang; Yan, Jun [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Wang, Hua, E-mail: wanghualjh@gmail.com [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Wang, Li-Sheng, E-mail: wangls@nic.bmi.ac.cn [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)

    2010-03-19

    Spreds, a recently established class of negative regulators of the Ras-ERK (extracellular signal-regulated kinase) pathway, are involved in hematogenesises, allergic disorders and tumourigenesis. However, their role in hematologic neoplasms is largely unknown. Possible effects of Spreds on other signal pathways closely related to Ras-ERK have been poorly investigated. In this study, we investigated the in vitro effects of Spred2 on chronic myeloid leukemia (CML) cells. In addition to inhibiting the well-established Ras-ERK cascade, adenovirus-mediated Spred2 over-expression inhibits constitutive and stem cell factor (SCF)-stimulated sphingosine kinase-1 (SPHK1) and Mcl-1 expression, as well as inhibiting proliferation and inducing apoptosis in CML cells. In K562 cells and primary CML cells, imatinib induces endogenous Spred2 expression. Spred2 silencing by stable RNA interference partly protects K562 cells against imatinib-induced apoptosis. Together, these data implicate Spred2 in imatinib-induced cytotoxicity in CML cells, possibly by inhibiting the Ras-ERK cascade and the pro-survival signaling molecules SPHK1 and Mcl-1. These findings reveal potential targets for selective therapy of CML.

  20. Philadelphia chromosome detection in chronic myeloid leukemia: Utility of phytohemagglutinin-stimulated peripheral blood culture

    Directory of Open Access Journals (Sweden)

    Man Updesh Singh Sachdeva

    2012-01-01

    Full Text Available Background: The conventional cytogenetic approach to demonstrate Philadelphia (Ph chromosome at times does not yield enough number of metaphases or are of suboptimal quality. Further, the rapid molecular tests have completely pushed this simple technique into disrepute. Aims: This study aimed to evaluate usefulness of phytohemagglutinin (PHA-stimulated peripheral blood culture for detection of Ph chromosome in chronic myeloid leukemia (CML patients. Materials and Methods: Fifty-six patients, including 11 newly diagnosed cases of CML and 45 patients of CML on imatinib therapy showing the presence of Ph chromosome in unstimulated samples, were included in the study. Cytogenetic analysis was done on unstimulated samples, i.e. bone marrow aspirate, 24- and 48-h peripheral blood culture, and compared with PHA-stimulated 72-h peripheral blood culture. Results: The preparations from PHA-stimulated peripheral blood culture samples in all 56 patients yielded high number of good-quality metaphases. All the 11 (100% newly diagnosed patients and 39/45 (87% of the patients on imatinib therapy showed the presence of Ph chromosome in PHA-stimulated samples. Addition of PHA-stimulated 72-h peripheral blood culture preparation can be of use for increasing the diagnostic yield in cases of CML with suboptimal results on conventional cytogenetics from bone marrow aspirate sample.