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Sample records for cell leukemia virus

  1. Selective host range restriction of goat cells for recombinant murine leukemia virus and feline leukemia virus type A.

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    Fischinger, P J; Thiel, H J; Blevins, C S; Dunlop, N M

    1981-01-01

    We isolated a strain of normal goat fibroblasts which was uniquely selective in that it allowed the replication of xenotropic murine leukemia virus but not polytropic recombinant murine leukemia virus. In addition, feline leukemia virus type A replication was severely diminished in these goat cells, whereas feline leukemia virus type B and feline endogenous RD114-CCC viruses replicated efficiently. No other known cells exhibit this pattern of virus growth restriction. These goat cells allow t...

  2. Formation of infectious hybrid virions with gibbon ape leukemia virus and human T-cell leukemia virus retroviral envelope glycoproteins and the gag and pol proteins of Moloney murine leukemia virus.

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    C. Wilson; Reitz, M S; Okayama, H; Eiden, M V

    1989-01-01

    The gibbon ape leukemia virus, SEATO strain, and human T-cell leukemia virus type I envelope glycoproteins can be functionally assembled with a Moloney murine leukemia virus core into infectious particles. The envelope-host cell receptor interaction is the major determinant of the host cell specificity for these hybrid virions.

  3. Target cells involved in radiation and radiation leukemia virus leukemogenesis

    International Nuclear Information System (INIS)

    Comparative studies concerned with the induction and early proliferation phases of preleukemic cells in relation to host environments using radiation or radiation leukemia virus as the leukemogenic agents, indicated different developmental pathways. The lack of thymus in mice exposed to fractionated irradiation did not prevent preleukemic cell induction but did interfere with the incidence of RadLV induced preleukemic cells. Thymus removal within several days following RadLV inoculation prevented the establishment of preleukemic cells in the bone marrow. The radiation induced preleukemic cells in the bone marrow. The radiation induced preleukemic cells were not lysed by anti-Thy-1.2 serum treatment and guinea pig complement whereas the RadLV induced ones were lysed to different degrees. Elimination of Thy-1.2 bearing cells from the virus induced preleukemic population reduced the development of overt T leukemias of donor origin. The thymus seemed of essential importance for establishing the proliferation of RadLV induced preleukemic cells but not for those induced by fractionated irradiation

  4. The receptors for gibbon ape leukemia virus and amphotropic murine leukemia virus are not downregulated in productively infected cells

    Directory of Open Access Journals (Sweden)

    Eiden Maribeth V

    2011-07-01

    Full Text Available Abstract Background Over the last several decades it has been noted, using a variety of different methods, that cells infected by a specific gammaretrovirus are resistant to infection by other retroviruses that employ the same receptor; a phenomenon termed receptor interference. Receptor masking is thought to provide an earlier means of blocking superinfection, whereas receptor down regulation is generally considered to occur in chronically infected cells. Results We used replication-competent GFP-expressing viruses containing either an amphotropic murine leukemia virus (A-MLV or the gibbon ape leukemia virus (GALV envelope. We also constructed similar viruses containing fluorescence-labeled Gag proteins for the detection of viral particles. Using this repertoire of reagents together with a wide range of antibodies, we were able to determine the presence and availability of viral receptors, and detect viral envelope proteins and particles presence on the cell surface of chronically infected cells. Conclusions A-MLV or GALV receptors remain on the surface of chronically infected cells and are detectable by respective antibodies, indicating that these receptors are not downregulated in these infected cells as previously proposed. We were also able to detect viral envelope proteins on the infected cell surface and infected cells are unable to bind soluble A-MLV or GALV envelopes indicating that receptor binding sites are masked by endogenously expressed A-MLV or GALV viral envelope. However, receptor masking does not completely prevent A-MLV or GALV superinfection.

  5. Susceptibility of human primary neuronal cells to Xenotropic Murine Leukemia Virus-related (XMRV virus infection

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    Girisetty Mohan

    2011-09-01

    Full Text Available Abstract Background Xenotropic Murine Leukemia Virus-related (XMRV virus is a recently identified mouse gammaretrovirus that has the ability to infect certain human cells. In this study, we investigated the susceptibility of primary neuronal cell types to infection with XMRV. Findings We observed that the human primary progenitors, progenitor-derived neurons, and progenitor-derived astrocytes supported XMRV multiplication. Interestingly, both progenitors and progenitor-derived neurons were more susceptible compared with progenitor-derived astrocytes. In addition, XMRV-infected Jurkat cells were able to transmit infection to neuronal cells. Conclusions These data suggest that neuronal cells are susceptible for XMRV infection.

  6. Human T cell leukemia virus type 1 infection drives spontaneous proliferation of natural killer cells

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    Norris, Philip J; Hirschkorn, Dale F.; DeVita, Deborah A.; Lee, Tzong-Hae; Murphy, Eedward L

    2010-01-01

    Most human T cell leukemia virus type 1 (HTLV-1) infected subjects remain asymptomatic throughout their lives, with a few individuals developing HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T cell leukemia. Lymphocytes from about half of HTLV-1 infected subjects spontaneously proliferate in vitro, and how this phenomenon relates to symptomatic disease outcome and viral burden is poorly understood. Spontaneous proliferation was measured in lymphocyte subsets, an...

  7. Cell surface antigens of radiation leukemia virus-induced BALB/c leukemias defined by syngeneic cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    Two cell surface antigens of mouse leukemias were defined by BALB/c cytotoxic T lymphocytes (CTL) generated against syngeneic radiation leukemia virus (RadLV)-induced leukemia, BALBRV1 or BALBRVD. Hyperimmunization of BALB/c mice with irradiated leukemias followed by in vitro sensitization of primed spleen cells resulted in the generation of CTL with high killing activity. The specificity of CTL was examined by direct cytotoxicity assays and competitive inhibition assays. A shared cell surface antigen, designated as BALBRV1 antigen, was detected by BALB/c anti-BALBRV1 CTL. BALBRV1 antigen was expressed not only on RadLV-induced BALB/c leukemias except for BALBRVD, but also on spontaneous or X-ray-induced BALB/c leukemias, chemically-induced leukemias with the H-2d haplotype and some chemically-induced BALB/c sarcomas. In contrast, a unique cell surface antigen, designated as BALBRVD antigen, was detected by BALB/c anti-BALBRVD CTL. BALBRVD antigen was expressed only on BALBRVD, but not on thirty-nine normal lymphoid or tumor cells. These two antigens could be distinguished from those previously defined on Friend, Moloney, Rauscher or Gross murine leukemia virus (MuLV) leukemias, or MuLV-related antigens. Both cytotoxic responses were blocked by antisera against H-2Kd, but not H-2Dd. The relationship of BALBRV1 antigen and BALBRVD antigen to endogenous MuLV is discussed with regard to the antigenic distribution on tumor cell lines. (author)

  8. Human monoclonal antibody directed against an envelope glycoprotein of human T-cell leukemia virus type I.

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    Matsushita, S; Robert-Guroff, M; Trepel, J. (Jane); Cossman, J; Mitsuya, H; Broder, S

    1986-01-01

    We report the production and characterization of a human monoclonal antibody reactive against the major envelope glycoprotein of human T-cell leukemia virus type I (HTLV-I), a virus linked to the etiology of adult T-cell leukemia. We exposed lymph-node cells derived from a patient with adult T-cell leukemia to the Epstein-Barr virus in vitro and obtained a B-cell clone (designated 0.5 alpha) by a limiting dilution technique. The secreted product of 0.5 alpha is a monoclonal antibody (also des...

  9. Animals Models of Human T Cell Leukemia Virus Type I Leukemogenesis.

    Science.gov (United States)

    Niewiesk, Stefan

    2016-03-31

    Infection with human T cell leukemia virus type I (HTLV-I) causes adult T cell leukemia (ATL) in a minority of infected individuals after long periods of viral persistence. The various stages of HTLV-I infection and leukemia development are studied by using several different animal models: (1) the rabbit (and mouse) model of persistent HTLV-I infection, (2) transgenic mice to model tumorigenesis by HTLV-I specific protein expression, (3) ATL cell transfers into immune-deficient mice, and (4) infection of humanized mice with HTLV-I. After infection, virus replicates without clinical disease in rabbits and to a lesser extent in mice. Transgenic expression of both the transactivator protein (Tax) and the HTLV-I bZIP factor (HBZ) protein have provided insight into factors important in leukemia/lymphoma development. To investigate factors relating to tumor spread and tissue invasion, a number of immune-deficient mice based on the severe combined immunodeficiency (SCID) or non-obese diabetic/SCID background have been used. Inoculation of adult T cell leukemia cell (lines) leads to lymphoma with osteolytic bone lesions and to a lesser degree to leukemia development. These mice have been used extensively for the testing of anticancer drugs and virotherapy. A recent development is the use of so-called humanized mice, which, upon transfer of CD34(+)human umbilical cord stem cells, generate human lymphocytes. Infection with HTLV-I leads to leukemia/lymphoma development, thus providing an opportunity to investigate disease development with the aid of molecularly cloned viruses. However, further improvements of this mouse model, particularly in respect to the development of adaptive immune responses, are necessary. PMID:27034390

  10. Quantitation, in vitro propagation, and characterization of preleukemic cells induced by radiation leukemia virus

    International Nuclear Information System (INIS)

    Intrathymic (i.t.) inoculation of radiation leukemia virus into C57BL/6 mice induces a population of preleukemic (PL) cells that can progress into mature thymic lymphomas upon transfer into syngeneic recipients. A minimum of 10(3) PL thymic cells are required to induce lymphomas in the recipient. Most of the individual lymphomas developed in mice which were inoculated with cells of a single PL thymus, derived from different T-cell precursors. PL thymic cells could be grown in vitro on a feeder layer consisting of splenic stromal cells. Growth medium was supplemented with supernatant harvested from an established radiation leukemia virus-induced lymphoma cell line (SR4). The in vitro-grown PL cells were characterized as Thy-1+, CD4+, CD8- T-cells, most of which expressed radiation leukemia virus antigens. Cultured PL cells were found to be nontumorigenic, based on their inability to form s.c. tumors. However, these cells could develop into thymic lymphomas if inoculated i.t. into syngeneic recipients. A culture of PL cells, maintained for 2 mo, showed clonal T-cell receptor arrangement. Lymphomas which developed in several recipient mice upon injection with these PL cells were found to possess the same T-cell receptor arrangement. These results indicate that PL cells can be adapted for in vitro growth while maintaining their preleukemic character

  11. Protein stabilization explains the gag requirement for transformation of lymphoid cells by Abelson murine leukemia virus

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    Prywes, R; Hoag, J; Rosenberg, N; Baltimore, D

    1985-01-01

    The single protein encoded by Abelson murine leukemia virus is a fusion of sequence from the retroviral gag genes with the v-abl sequence. Deletion of most of the gag region from the transforming protein results in a virus capable of transforming fibroblasts but no longer capable of transforming lymphoid cells. Smaller deletions in gag reveal that p15 gag sequences are responsible for this effect, whereas deletion of p12 sequences had no effect on lymphoid transformation. In transformed fibro...

  12. Androgen-independent proliferation of LNCaP prostate cancer cells infected by xenotropic murine leukemia virus-related virus

    Energy Technology Data Exchange (ETDEWEB)

    Kakoki, Katsura [Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Department of AIDS Research, Institute of Tropical Medicine, G-COE, Nagasaki University, Nagasaki 852-8523 (Japan); Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kamiyama, Haruka [Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Department of AIDS Research, Institute of Tropical Medicine, G-COE, Nagasaki University, Nagasaki 852-8523 (Japan); Izumida, Mai; Yashima, Yuka; Hayashi, Hideki [Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Yamamoto, Naoki [Department of AIDS Research, Institute of Tropical Medicine, G-COE, Nagasaki University, Nagasaki 852-8523 (Japan); Department of Microbiology, National University of Singapore (Singapore); Matsuyama, Toshifumi [Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Igawa, Tsukasa; Sakai, Hideki [Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kubo, Yoshinao, E-mail: yoshinao@nagasaki-u.ac.jp [Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Department of AIDS Research, Institute of Tropical Medicine, G-COE, Nagasaki University, Nagasaki 852-8523 (Japan)

    2014-04-25

    Highlights: • XMRV infection induces androgen-independent growth in LNCaP cells. • XMRV infection reduces expression of androgen receptor. • XMRV promotes appearance of androgen blocker-resistant prostate cancer cells. - Abstract: Xenotropic murine leukemia virus-related virus (XMRV) is a novel gammaretrovirus that was originally isolated from human prostate cancer. It is now believed that XMRV is not the etiologic agent of prostate cancer. An analysis of murine leukemia virus (MLV) infection in various human cell lines revealed that prostate cancer cell lines are preferentially infected by XMRV, and this suggested that XMRV infection may confer some sort of growth advantage to prostate cancer cell lines. To examine this hypothesis, androgen-dependent LNCaP cells were infected with XMRV and tested for changes in certain cell growth properties. We found that XMRV-infected LNCaP cells can proliferate in the absence of the androgen dihydrotestosterone. Moreover, androgen receptor expression is significantly reduced in XMRV-infected LNCaP cells. Such alterations were not observed in uninfected and amphotropic MLV-infected LNCaP cells. This finding explains why prostate cancer cell lines are preferentially infected with XMRV.

  13. Androgen-independent proliferation of LNCaP prostate cancer cells infected by xenotropic murine leukemia virus-related virus

    International Nuclear Information System (INIS)

    Highlights: • XMRV infection induces androgen-independent growth in LNCaP cells. • XMRV infection reduces expression of androgen receptor. • XMRV promotes appearance of androgen blocker-resistant prostate cancer cells. - Abstract: Xenotropic murine leukemia virus-related virus (XMRV) is a novel gammaretrovirus that was originally isolated from human prostate cancer. It is now believed that XMRV is not the etiologic agent of prostate cancer. An analysis of murine leukemia virus (MLV) infection in various human cell lines revealed that prostate cancer cell lines are preferentially infected by XMRV, and this suggested that XMRV infection may confer some sort of growth advantage to prostate cancer cell lines. To examine this hypothesis, androgen-dependent LNCaP cells were infected with XMRV and tested for changes in certain cell growth properties. We found that XMRV-infected LNCaP cells can proliferate in the absence of the androgen dihydrotestosterone. Moreover, androgen receptor expression is significantly reduced in XMRV-infected LNCaP cells. Such alterations were not observed in uninfected and amphotropic MLV-infected LNCaP cells. This finding explains why prostate cancer cell lines are preferentially infected with XMRV

  14. A transgenic mouse model of human T-cell leukemia virus type I (HTLV-1–associated diseases

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    Takeo eOhsugi

    2013-03-01

    Full Text Available Human T-cell leukemia virus type I (HTLV-1 is the etiological agent of adult T-cell leukemia/lymphoma (ATLL and several inflammatory diseases. Tax, the protein encoded by HTLV-1, may be responsible for the development of the diseases caused by this virus. To investigate the pathogenic role of Tax, several transgenic mouse strains expressing Tax have been developed in recent years. These mice develop various tumors including large granular lymphocytic leukemia, as well as inflammatory diseases such as arthritis. These results suggest that Tax expression alone is sufficient to cause both malignant neoplastic diseases and inflammatory diseases. However, until recently, there were no tax transgenic mice that develop T-cell leukemia and lymphoma resembling ATLL. The first successful induction of leukemia in T cells was pre–T-cell leukemia generated in transgenic mice in which a mouse lymphocyte-specific protein tyrosine kinase p56lck (lck proximal promoter was used to express the tax gene in immature T cells. Subsequently, transgenic mice were established in which the lck-distal promoter was used to express Tax in mature T cells; these mice developed mature T-cell leukemia and lymphoma that more closely resembled ATLL than did earlier mouse models.

  15. Crystal structures of inhibitor complexes of human T-cell leukemia virus (HTLV-1) protease

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    Satoh, Tadashi; Li, Mi; Nguyen, Jeffrey-Tri; Kiso, Yoshiaki; Gustchina, Alla; Wlodawer, Alexander (NCI); (Kyoto)

    2010-09-28

    Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus associated with several serious diseases, such as adult T-cell leukemia and tropical spastic paraparesis/myelopathy. For a number of years, the protease (PR) encoded by HTLV-1 has been a target for designing antiviral drugs, but that effort was hampered by limited available structural information. We report a high-resolution crystal structure of HTLV-1 PR complexed with a statine-containing inhibitor, a significant improvement over the previously available moderate-resolution structure. We also report crystal structures of the complexes of HTLV-1 PR with five different inhibitors that are more compact and more potent. A detailed study of structure-activity relationships was performed to interpret in detail the influence of the polar and hydrophobic interactions between the inhibitors and the protease.

  16. Crystal Structures of Inhibitir Complexes of Human T-Cell Leukemia Virus (HTLV-1) Protease

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    Satoh, Tadashi; Li, Mi; Nguyen, Jeffrey-Tri; Kiso, Yoshiaki; Gustchina, Alla; Wlodawer, Alexander (NCI); (Kyoto)

    2010-09-17

    Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus associated with several serious diseases, such as adult T-cell leukemia and tropical spastic paraparesis/myelopathy. For a number of years, the protease (PR) encoded by HTLV-1 has been a target for designing antiviral drugs, but that effort was hampered by limited available structural information. We report a high-resolution crystal structure of HTLV-1 PR complexed with a statine-containing inhibitor, a significant improvement over the previously available moderate-resolution structure. We also report crystal structures of the complexes of HTLV-1 PR with five different inhibitors that are more compact and more potent. A detailed study of structure-activity relationships was performed to interpret in detail the influence of the polar and hydrophobic interactions between the inhibitors and the protease.

  17. Infectious complications of human T cell leukemia/lymphoma virus type I infection.

    Science.gov (United States)

    Marsh, B J

    1996-07-01

    Infection with human T cell leukemia/lymphoma virus type I (HTLV-I) has been etiologically associated with two diseases: adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. Increasing evidence suggests that HTLV-I infection may be associated with immunosuppression and, as a consequence, affect the risk and expression of several other infectious diseases, of which the best studied are strongyloidiasis, tuberculosis, and leprosy. In strongyloidiasis, coinfection with HTLV-I appears to result in a higher rate of chronic carriage, an increased parasite load, and a risk of more severe infection. In tuberculosis, a decrease in delayed-type hypersensitivity to Mycobacterium tuberculosis has been established, but whether this decrease is clinically significant has yet to be determined. In leprosy, an increased risk of disease is suggested, but the published studies are all too poorly controlled to draw definite conclusions. PMID:8816143

  18. Investigation of the Bovine Leukemia Virus Proviral DNA in Human Leukemias and Lung cancers in Korea

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    Lee, JeHoon; Kim, Yonggoo; Kang, Chang Suk; Cho, Dae Hyun; Shin, Dong Hwan; Yum, Young Na; Oh, Jae Ho; Kim, Sheen Hee; Hwang, Myung Sil; Lim, Chul Joo; Yang, Ki Hwa; Han, Kyungja

    2005-01-01

    The bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis. This study investigated the presence of the BLV in leukemia (179 acute lymphoblastic leukemia, 292 acute myeloid leukemia and 46 chronic myelogenous leukemia cases) and 162 lung cancer patients (139 adenocarcinoma, 23 squamous cell carcinoma) to determine if the BLV is a causative organism of leukemia and lung cancer in Koreans. A BLV infection was confirmed in human cells by PCR using a BLV-8 primer combinati...

  19. Human T-cell leukemia virus types I and II exhibit different DNase I protection patterns

    International Nuclear Information System (INIS)

    Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are human retroviruses which normally infect T-lymphoid cells. HTLV-I infection is associated with adult T-cell leukemia-lymphoma, and HTLV-II is associated with an indolent form of hairy-cell leukemia. To identify potential transcriptional regulatory elements of these two related human retroviruses, the authors performed DNase I footprinting of both the HTLV-I and HTLV-II long terminal repeats (LTRs) by using extracts prepared from uninfected T cells, HTLV-I and HTLV-II transformed T cells, and HeLa cells. Five regions of the HTLV-I LTR and three regions of the HTLV-II LTR showed protection by DNase I footprinting. All three of the 21-base-pair repeats previously shown to be important in HTLV transcriptional regulation were protected in the HTLV-I LTR, whereas only one of these repeats was protected in the HTLV-II LTR. Several regions exhibited altered protection in extracts prepared from lymphoid cells as compared with HeLa cells, but there were minimal differences in the protection patterns between HTLV-infected and uninfected lymphoid extracts. A number of HTLV-I and HTLV-II LTR fragments which contained regions showing protection in DNase I footprinting were able to function as inducible enhancer elements in transient CAT gene expression assays in the presence of the HTLV-II tat protein. The alterations in the pattern of the cellular proteins which bind to the HTLV-I and HTLV-II LTRs may in part be responsible for differences in the transcriptional regulation of these two related viruses

  20. Type C virus particles produced in human T-cell lines derived from acute lymphoblastic leukemia and a leukemic T-lymphoid malignancy.

    Directory of Open Access Journals (Sweden)

    Oda,Takuzo

    1983-12-01

    Full Text Available Electron microscopy of four human T-cell lines revealed the production of type C virus particles in two T-cell lines: one derived from acute lymphoblastic leukemia and the other from a leukemic T-lymphoid malignancy. Virus particles isolated from these cells had reverse transcriptase activity and the major internal structural protein of 30,000 daltons (p30. The indirect immunofluorescence test of these virus-producing cells with sera of patients with adult T-cell leukemia (ATL was negative. The data indicate that these retroviruses are different from adult T-cell leukemia virus (ATLV.

  1. The increased susceptibility of hematopoietic stem cells to Friend leukemia virus in the repopulating period

    International Nuclear Information System (INIS)

    The present study considers two fundamental problems of leukemia and stem cells: (1) whether the target cells for malignant transformation of Friend leukemia virus (FV) are the pluripotential stem cells; (2) whether the susceptibility of the target cell is changeable depending on the proliferating state of the cell. In the experiments, inbred 8- to 12-week-old C3H/He and BC3Fl hybrid mice were used. As target cells for FV, two candidate cell populations should be considered. These are the pluripotential stem cells expressed as CFUs and the committed stem cells expressed as erythropoietin-responsive cells (ERC). According to our preliminary experiments on the recovery patterns of CFUs or ERC, after a single 150 rads X-irradiation (X) or administration of 215 mg/kg of cyclophosphamide (CY), it was clear that the repopulation of CFUs was quite different from that of ERC. The target cells for FV-induced transformation are the stem cells expressed as CFUs and the susceptibility of these increases under conditions of active repopulation after X-irradiation and cyclophosphamide administration. After the irradiation especially, this effect is dose-dependent for doses over 25 rads at 2 weeks after irradiation. (Auth.)

  2. Crystal structure of human T cell leukemia virus protease, a novel target for anticancer drug design

    OpenAIRE

    Li, Mi; Laco, Gary S.; Jaskolski, Mariusz; Rozycki, Jan; Alexandratos, Jerry; Wlodawer, Alexander; Gustchina, Alla

    2005-01-01

    The successful development of a number of HIV-1 protease (PR) inhibitors for the treatment of AIDS has validated the utilization of retroviral PRs as drug targets and necessitated their detailed structural study. Here we report the structure of a complex of human T cell leukemia virus type 1 (HTLV-1) PR with a substrate-based inhibitor bound in subsites P5 through P5′. Although HTLV-1 PR exhibits an overall fold similar to other retroviral PRs, significant structural differences are present i...

  3. Intracellular assembly and budding of the Murine Leukemia Virus in infected cells

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    Briant Laurence

    2006-02-01

    Full Text Available Abstract Background Murine Leukemia Virus (MLV assembly has been long thought to occur exclusively at the plasma membrane. Current models of retroviral particle assembly describe the recruitment of the host vacuolar protein sorting machinery to the cell surface to induce the budding of new particles. Previous fluorescence microscopy study reported the vesicular traffic of the MLV components (Gag, Env and RNA. Here, electron microscopy (EM associated with immunolabeling approaches were used to go deeply into the assembly of the "prototypic" MLV in chronically infected NIH3T3 cells. Results Beside the virus budding events seen at the cell surface of infected cells, we observed that intracellular budding events could also occur inside the intracellular vacuoles in which many VLPs accumulated. EM in situ hybridization and immunolabeling analyses confirmed that these latter were MLV particles. Similar intracellular particles were detected in cells expressing MLV Gag alone. Compartments containing the MLV particles were identified as late endosomes using Lamp1 endosomal/lysosomal marker and BSA-gold pulse-chase experiments. In addition, infectious activity was detected in lysates of infected cells. Conclusion Altogether, our results showed that assembly of MLV could occur in part in intracellular compartments of infected murine cells and participate in the production of infectious viruses. These observations suggested that MLV budding could present similarities with the particular intracellular budding of HIV in infected macrophages.

  4. ADULT T CELL LEUKEMIA LYMPHOMA

    OpenAIRE

    Neely, S. M.

    2004-01-01

    Adult T cell leukemia lymphoma (ATLL) is a CD4+ lymphoproliferative malignancy resulting from human T-cell leukemia virus type 1 (HTLV1) infection. It includes differing clinical forms classified as smoldering, chronic, lymphomatous, and acute ATLL. The Tax protein of HTLV-1 has been implicated as a viral oncoprotein which enhances virus replication and alters cellular gene expression, including activation of nuclear factor kappa B (NF kB), to result in lymphoid transformation. Chemotherapy f...

  5. Friend and Moloney murine leukemia viruses specifically recombine with different endogenous retroviral sequences to generate mink cell focus-forming viruses.

    OpenAIRE

    Evans, L H; Cloyd, M W

    1985-01-01

    A group of mink cell focus-forming (MCF) viruses was derived by inoculation of NFS/N mice with Moloney murine leukemia virus (Mo-MuLV 1387) and was compared to a similarly derived group of MCF viruses from mice inoculated with Friend MuLV (Fr-MuLV 57). Antigenic analyses using monoclonal antibodies specific for MCF virus and xenotropic MuLV envelope proteins and genomic structural analyses by RNase T1-resistant oligonucleotide finger-printing indicated that the Moloney and Friend MCF viruses ...

  6. Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms

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    Mueller Nancy

    2005-10-01

    Full Text Available Abstract Background Human T-cell leukemia virus type I (HTLV-I causes adult T-cell leukemia (ATL after a long latent period. Among accessory genes encoded by HTLV-I, the tax gene is thought to play a central role in oncogenesis. However, Tax expression is disrupted by several mechanims including genetic changes of the tax gene, deletion/hypermethylation of 5'-LTR. To clarify the role of epigenetic changes, we analyzed DNA methylation and histone modification in the whole HTLV-I provirus genome. Results The gag, pol and env genes of HTLV-I provirus were more methylated than pX region, whereas methylation of 5'-LTR was variable and 3'-LTR was not methylated at all. In ATL cell lines, complete DNA methylation of 5'-LTR was associated with transcriptional silencing of viral genes. HTLV-I provirus was more methylated in primary ATL cells than in carrier state, indicating the association with disease progression. In seroconvertors, DNA methylation was already observed in internal sequences of provirus just after seroconversion. Taken together, it is speculated that DNA methylation first occurs in the gag, pol and env regions and then extends in the 5' and 3' directions in vivo, and when 5'-LTR becomes methylated, viral transcription is silenced. Analysis of histone modification in the HTLV-I provirus showed that the methylated provirus was associated with hypoacetylation. However, the tax gene transcript could not be detected in fresh ATL cells regardless of hyperacetylated histone H3 in 5'-LTR. The transcription rapidly recovered after in vitro culture in such ATL cells. Conclusion These results showed that epigenetic changes of provirus facilitated ATL cells to evade host immune system by suppressing viral gene transcription. In addition, this study shows the presence of another reversible mechanism that suppresses the tax gene transcription without DNA methylation and hypoacetylated histone.

  7. Production of antigen-specific suppressive T cell factor by radiation leukemia virus-transformed suppressor T cells.

    OpenAIRE

    Ricciardi-Castagnoli, P; Doria, G; Adorini, L

    1981-01-01

    Hen egg-white lysozyme (HEL)-specific suppressor T cells induced in C57BL/6 mice have been selected by sequential passage over plates coated with goat anti-mouse Ig and HEL. These suppressor T cells, 80% I-J+, were infected in vitro with radiation leukemia virus (RadLV/Nu1) and injected intravenously into sublethally irradiated syngeneic recipients. After 4-6 months, 6 out of 20 injected mice developed thymic lymphomas, which were maintained by transplantation into histocompatible hosts and s...

  8. Cross Talk between Expression of the Human T-Cell Leukemia Virus Type 1 Tax Transactivator and the Oncogenic bHLH Transcription Factor TAL1▿ †

    OpenAIRE

    Terme, Jean-Michel; Wencker, Melanie; Favre-Bonvin, Arnaud; Bex, Françoise; Gazzolo, Louis; Duc Dodon, Madeleine; Jalinot, Pierre

    2008-01-01

    The human T-cell leukemia virus type 1 (HTLV-1) Tax transactivator is known to induce or repress various cellular genes, several of them encoding transcription factors. As Tax is known to deregulate various basic bHLH factors, we looked more specifically at its effect on TAL1 (T-cell acute lymphoblastic leukemia 1), also known as SCL (stem cell leukemia). Indeed, TAL1 is deregulated in a high percentage of T-cell acute lymphoblastic leukemia cells, and its oncogenic properties are well-establ...

  9. Distinct Morphology of Human T-Cell Leukemia Virus Type 1-Like Particles.

    Science.gov (United States)

    Maldonado, José O; Cao, Sheng; Zhang, Wei; Mansky, Louis M

    2016-01-01

    The Gag polyprotein is the main retroviral structural protein and is essential for the assembly and release of virus particles. In this study, we have analyzed the morphology and Gag stoichiometry of human T-cell leukemia virus type 1 (HTLV-1)-like particles and authentic, mature HTLV-1 particles by using cryogenic transmission electron microscopy (cryo-TEM) and scanning transmission electron microscopy (STEM). HTLV-1-like particles mimicked the morphology of immature authentic HTLV-1 virions. Importantly, we have observed for the first time that the morphology of these virus-like particles (VLPs) has the unique local feature of a flat Gag lattice that does not follow the curvature of the viral membrane, resulting in an enlarged distance between the Gag lattice and the viral membrane. Other morphological features that have been previously observed with other retroviruses include: (1) a Gag lattice with multiple discontinuities; (2) membrane regions associated with the Gag lattice that exhibited a string of bead-like densities at the inner leaflet; and (3) an arrangement of the Gag lattice resembling a railroad track. Measurement of the average size and mass of VLPs and authentic HTLV-1 particles suggested a consistent range of size and Gag copy numbers in these two groups of particles. The unique local flat Gag lattice morphological feature observed suggests that HTLV-1 Gag could be arranged in a lattice structure that is distinct from that of other retroviruses characterized to date. PMID:27187442

  10. Lethal cutaneous disease in transgenic mice conditionally expressing type I human T cell leukemia virus Tax.

    Science.gov (United States)

    Kwon, Hakju; Ogle, Louise; Benitez, Bobby; Bohuslav, Jan; Montano, Mauricio; Felsher, Dean W; Greene, Warner C

    2005-10-21

    Type I human T cell leukemia virus (HTLV-I) is etiologically linked with adult T cell leukemia, an aggressive and usually fatal expansion of activated CD4+ T lymphocytes that frequently traffic to skin. T cell transformation induced by HTLV-I involves the action of the 40-kDa viral Tax transactivator protein. Tax both stimulates the HTLV-I long terminal repeat and deregulates the expression of select cellular genes by altering the activity of specific host transcription factors, including cyclic AMP-responsive element-binding protein (CREB)/activating transcription factor, NF-kappaB/Rel, and serum response factor. To study initiating events involved in HTLV-I Tax-induced T cell transformation, we generated "Tet-off" transgenic mice conditionally expressing in a lymphocyte-restricted manner (EmuSR alpha promoter-enhancer) either wild-type Tax or mutant forms of Tax that selectively compromise the NF-kappaB (M22) or CREB/activating transcription factor (M47) activation pathways. Wild-type Tax and M47 Tax-expressing mice, but not M22-Tax expressing mice, developed progressive alopecia, hyperkeratosis, and skin lesions containing profuse activated CD4 T cell infiltrates with evidence of deregulated inflammatory cytokine production. In addition, these animals displayed systemic lymphadenopathy and splenomegaly. These findings suggest that Tax-mediated activation of NF-kappaB plays a key role in the development of this aggressive skin disease that shares several features in common with the skin disease occurring during the preleukemic stage in HTLV-I-infected patients. Of note, this skin disease completely resolved when Tax transgene expression was suppressed by administration of doxycycline, emphasizing the key role played by this viral oncoprotein in the observed pathology. PMID:16105841

  11. Fusogenic segments of bovine leukemia virus and simian immunodeficiency virus are interchangeable and mediate fusion by means of oblique insertion in the lipid bilayer of their target cells.

    OpenAIRE

    Vonèche, V; Portetelle, D; Kettmann, R; Willems, L; Limbach, K.; E. Paoletti; Ruysschaert, J M; Burny, A; Brasseur, R.

    1992-01-01

    Modified bovine leukemia virus (BLV) glycoproteins were expressed by using vaccinia virus recombinants, and their fusogenic capacities were examined by a syncytia-formation assay. This analysis indicates that (i) both BLV envelope glycoproteins gp51 and gp30 are necessary for cell fusion; (ii) insertion of the N-terminal segment of gp30 (fusion peptide) into the lipid bilayer in an oblique orientation, as predicted by computer conformational analysis, results in fusogenic capacities higher th...

  12. [Adult T-cell lymphoma/leukemia associated with HTLV-I virus in Martinique: apropos of 2 cases].

    Science.gov (United States)

    Gessain, A; Plumelle, Y; Sanhadji, K; Barin, F; Gazzolo, L; Constant-Desportes, M; Pascaline, N; Diebold, J; De-Thé, G

    1986-01-01

    Two HTLV-I associated adult T cell leukemia cases were observed in patient from Martinique (French West Indies). These case are similar to the clinical entity, described by Takatsuki in 1977 in Japan and by Catovsky in Caribbean patients, characterized by a lymphadenopathy, skin lesions and visceral involvement, hypercalcemia, an aggressive course, and poor prognosis. The malignant cells with T4 phenotype and often suppressive function, were pleomorphic, mature, with prominent nuclear irregularities. Systematic research of HTLV-I virus or antibodies in patients with this clinical picture, to measure the influence of this virus in T cell lymphoproliferative diseases in France and in French West Indies is required. PMID:3016639

  13. Cell Infectivity in Relation to Bovine Leukemia Virus gp51 and p24 in Bovine Milk Exosomes

    OpenAIRE

    Yamada, Tetsuya; Shigemura, Hiroaki; ISHIGURO, Naotaka; Inoshima, Yasuo

    2013-01-01

    Exosomes are small membranous microvesicles (40–100 nm in diameter) and are extracellularly released from a wide variety of cells. Exosomes contain microRNA, mRNA, and cellular proteins, which are delivered into recipient cells via these exosomes, and play a role in intercellular communication. In bovine leukemia virus (BLV) infection of cattle, although it is thought to be a minor route of infection, BLV can be transmitted to calves via milk. Here, we investigated the association between exo...

  14. Cell Infectivity in Relation to Bovine Leukemia Virus gp51 and p24 in Bovine Milk Exosomes

    OpenAIRE

    Tetsuya Yamada; Hiroaki Shigemura; Naotaka Ishiguro; Yasuo Inoshima

    2013-01-01

    Exosomes are small membranous microvesicles (40-100 nm in diameter) and are extracellularly released from a wide variety of cells. Exosomes contain microRNA, mRNA, and cellular proteins, which are delivered into recipient cells via these exosomes, and play a role in intercellular communication. In bovine leukemia virus (BLV) infection of cattle, although it is thought to be a minor route of infection, BLV can be transmitted to calves via milk. Here, we investigated the association between exo...

  15. Novel CD8(+) cytotoxic T cell epitopes in bovine leukemia virus with cattle.

    Science.gov (United States)

    Bai, Lanlan; Takeshima, Shin-Nosuke; Isogai, Emiko; Kohara, Junko; Aida, Yoko

    2015-12-16

    Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis and is closely related to human T cell leukemia virus (HTLV). The cytotoxic T lymphocyte (CTL) plays a key role in suppressing the progression of disease caused by BLV. T and B cell epitopes in BLV have been studied, but CD8(+) CTL epitopes remain poorly understood. We used a library of 115 synthetic peptides covering the entirety of the Env proteins (gp51 and gp30), the Gag proteins (p15, p24, and p12), and the Tax protein of BLV to identify 11 novel CD8(+) T cell epitopes (gp51N5, gp51N11, gp51N12, gp30N5, gp30N6, gp30N8, gp30N16, tax16, tax18, tax19, and tax20) in four calves experimentally infected with BLV. The number of CD8(+) T cell epitopes that could be identified in each calf correlated with the BLV proviral load. Interestingly, among the 11 epitopes identified, only gp51N11 was capable of inducing CD8(+) T cell-mediated cytotoxicity in all four calves, but it is not a suitable vaccine target because it shows a high degree of polymorphism according to the Wu-Kabat variability index. By contrast, no CTL epitopes were identified from the Gag structural protein. In addition, several epitopes were obtained from gp30 and Tax, indicating that cellular immunity against BLV is strongly targeted to these proteins. CD8(+) CTL epitopes from gp30 and Tax were less polymorphic than epitopes from. Indeed, peptides tax16, tax18, tax19, and tax20 include a leucine-rich activation domain that encompasses a transcriptional activation domain, and the gp30N16 peptide contains a proline-rich region that interacts with a protein tyrosine phosphatase SHP1 to regulate B cell activation. Moreover, at least one CD8(+) CTL epitope derived from gp30 was identified in each of the four calves. These results indicate that BLV gp30 may be the best candidate for the development of a BLV vaccine. PMID:26552001

  16. Phosphorylation regulates human T-cell leukemia virus type 1 Rex function

    Directory of Open Access Journals (Sweden)

    Ward Michael

    2009-11-01

    Full Text Available Abstract Background Human T-cell leukemia virus type 1 (HTLV-1 is a pathogenic complex deltaretrovirus, which is the causative agent of adult T-cell leukemia/lymphoma (ATL and HTLV-1-associated myelopathy/tropical spastic paraparesis. In addition to the structural and enzymatic viral gene products, HTLV-1 encodes the positive regulatory proteins Tax and Rex along with viral accessory proteins. Tax and Rex proteins orchestrate the timely expression of viral genes important in viral replication and cellular transformation. Rex is a nucleolar-localizing shuttling protein that acts post-transcriptionally by binding and facilitating the export of the unspliced and incompletely spliced viral mRNAs from the nucleus to the cytoplasm. HTLV-1 Rex (Rex-1 is a phosphoprotein and general protein kinase inhibition correlates with reduced function. Therefore, it has been proposed that Rex-1 function may be regulated through site-specific phosphorylation. Results We conducted a phosphoryl mapping of Rex-1 over-expressed in transfected 293 T cells using a combination of affinity purification and liquid chromatography tandem mass spectrometry. We achieved 100% physical coverage of the Rex-1 polypeptide and identified five novel phosphorylation sites at Thr-22, Ser-36, Thr-37, Ser-97, and Ser-106. We also confirmed evidence of two previously identified residues, Ser-70 and Thr-174, but found no evidence of phosphorylation at Ser-177. The functional significance of these phosphorylation events was evaluated using a Rex reporter assay and site-directed mutational analysis. Our results indicate that phosphorylation at Ser-97 and Thr-174 is critical for Rex-1 function. Conclusion We have mapped completely the site-specific phosphorylation of Rex-1 identifying a total of seven residues; Thr-22, Ser-36, Thr-37, Ser-70, Ser-97, Ser-106, and Thr-174. Overall, this work is the first to completely map the phosphorylation sites in Rex-1 and provides important insight into

  17. APOBEC3G targets human T-cell leukemia virus type 1

    Directory of Open Access Journals (Sweden)

    Imada Kazunori

    2005-05-01

    Full Text Available Abstract Background Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G is a host cellular protein with a broad antiviral activity. It inhibits infectivitiy of a wide variety of retroviruses by deaminating deoxycytidine (dC into deoxyuridine (dU in newly synthesized minus strand DNA, resulting in G-to-A hypermutation of the viral plus strand DNA. To clarify the mechanism of its function, we have examined the antiviral activity of APOBEC3G on human T-cell leukemia virus type 1 (HTLV-1, the first identified human retrovirus. Results In this study, we have demonstrated that overexpressed as well as endogenous APOBEC3G were incorporated into HTLV-1 virions and that APOBEC3G inhibited the infection of HTLV-1. Interestingly, several inactive mutants of APOBEC3G also inhibited HTLV-1 and no G-to-A hypermutation was induced by APOBEC3G in HTLV-1 genome. Furthermore, we introduced the human immunodeficiency virus type 1 (HIV-1 vif gene into HTLV-1 producing cell line, MT-2, to antagonize APOBEC3G by reducing its intracellular expression and virion incorporation, which resulted in upregulation of the infectivity of produced viruses. Conclusion APOBEC3G is incorporated into HTLV-1 virions and inhibits the infection of HTLV-1 without exerting its cytidine deaminase activity. These results suggest that APOBEC3G might act on HTLV-1 through different mechanisms from that on HIV-1 and contribute to the unique features of HTLV-1 infection and transmission.

  18. Type C virus particles produced in human T-cell lines derived from acute lymphoblastic leukemia and a leukemic T-lymphoid malignancy.

    OpenAIRE

    Oda, Takuzo; Watanabe,Sekiko; Nakamura,Takashi

    1983-01-01

    Electron microscopy of four human T-cell lines revealed the production of type C virus particles in two T-cell lines: one derived from acute lymphoblastic leukemia and the other from a leukemic T-lymphoid malignancy. Virus particles isolated from these cells had reverse transcriptase activity and the major internal structural protein of 30,000 daltons (p30). The indirect immunofluorescence test of these virus-producing cells with sera of patients with adult T-cell leukemia (ATL) was negative....

  19. [Sarcoidosis and leukemia/T-cell lymphoma associated with HTLV-1 virus infection in adults (apropos of a case)].

    Science.gov (United States)

    Panelatti, G; Plumelle, Y; Arfi, S; Pascaline, N; Caplanne, D; Jean-Baptiste, G

    1992-01-01

    The HTLV-1 virus causes a disturbance of the immune system, the evaluation of which is often difficult. We report a case of sarcoidosis in a 49 year old woman of Martinique as evidenced by bilateral hilar adenopathy, hypercalcaemia, uveitis and granulomatous lesions on histological examination. Serological was positive for HTLV-1 antibodies. Three years later she developed an adult T-cell leukemia/lymphoma. The relationships between the HTLV-1 retroviral infection and different pathologies observed are discussed. PMID:1287773

  20. Production of antigen-specific suppressive T cell factor by radiation leukemia virus-transformed suppressor T cells

    International Nuclear Information System (INIS)

    Hen egg-white lysozyme-specific suppressor T cells induced in C57BL/6 mice have been selected by sequential passage over plates coated with goat anti-mouse Ig and HEL. These suppressor T cells, 80% I-J+, were infected in vitro with radiation leukemia virus and injected intravenously into sublethally irradiated syngeneic recipients. After 4 to 6 months, 6 out of 20 injected mice developed thymic lymphomas, which were maintained by transplantation into histocompatible hosts and subsequently established as permanent cell lines. Cells of these six thymomas were screened for the presence of Thy 1.2, Lyt 1, Lyt 2, I-J/sup b/, and Ig cell surface antigens by direct or indirect immunofluorescence. One tumor was found to express the expected phenotype of suppressor T cells. High-speed supernatants of extracts obtained from L4 cells were able to induce HEL-specific suppression in a T cell proliferative assay, demonstrating the presence of an antigen-specific suppressive T cell factor

  1. Investigation of the bovine leukemia virus proviral DNA in human leukemias and lung cancers in Korea.

    Science.gov (United States)

    Lee, Jehoon; Kim, Yonggoo; Kang, Chang Suk; Cho, Dae Hyun; Shin, Dong Hwan; Yum, Young Na; Oh, Jae Ho; Kim, Sheen Hee; Hwang, Myung Sil; Lim, Chul Joo; Yang, Ki Hwa; Han, Kyungja

    2005-08-01

    The bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis. This study investigated the presence of the BLV in leukemia (179 acute lymphoblastic leukemia, 292 acute myeloid leukemia and 46 chronic myelogenous leukemia cases) and 162 lung cancer patients (139 adenocarcinoma, 23 squamous cell carcinoma) to determine if the BLV is a causative organism of leukemia and lung cancer in Koreans. A BLV infection was confirmed in human cells by PCR using a BLV-8 primer combination. All 517 cases of human leukemia and 162 lung cancer were negative for a PCR of the BLV proviral DNA. In conclusion, although meat has been imported from BLV endemic areas, the BLV infection does not appear to be the cause of human leukemia or lung cancer in Koreans. These results can be used as a control for further studies on the BLV in Koreans. PMID:16100451

  2. Analysis of Human T-Cell Leukemia Virus Type 1 Particles by Using Cryo-Electron Tomography

    Science.gov (United States)

    Cao, Sheng; Maldonado, José O.; Grigsby, Iwen F.

    2014-01-01

    The particle structure of human T-cell leukemia virus type 1 (HTLV-1) is poorly characterized. Here, we have used cryo-electron tomography to analyze HTLV-1 particle morphology. Particles produced from MT-2 cells were polymorphic, roughly spherical, and varied in size. Capsid cores, when present, were typically poorly defined polyhedral structures with at least one curved region contacting the inner face of the viral membrane. Most of the particles observed lacked a defined capsid core, which likely impacts HTLV-1 particle infectivity. PMID:25473052

  3. Regulation of expression driven by human immunodeficiency virus type 1 and human T-cell leukemia virus type I long terminal repeats in pluripotential human embryonic cells

    International Nuclear Information System (INIS)

    Human pluripotential embryonic teratocarcinoma cells differentially expressed gene activity controlled by the human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type I (HTLV-I) long terminal repeats (LTRs) when differentiation was induced by the morphogen all-trans retinoic acid. The alterations occurred after commitment and before the appearance of the multiple cell types characteristic of these pluripotential cells. After commitment, gene activity controlled by the HIV-1 LTR markedly increased, whereas that controlled by the HTLV-I LTR decreased. Steady-state mRNA levels and nuclear run-on transcription indicated that the increased HIV-1-directed activity during differentiation occurred posttranscriptionally, whereas the decreased HTLV-I activity was at the transcriptional level. Phorbol esters did not cause commitment but strongly enhanced expression by both viral LTRs at the transcriptional level. Differentiating cells gradually lost the ability to respond to phorbol ester stimulation. Experiments with a deletion mutant of the HIV-1 LTR suggested that this was due to imposition of negative regulation during differentiation that was not reversed by phorbol ester induction. Cycloheximide, with or without phorbol ester, slightly stimulated HIV-1-directed activity at the transcriptional level and massively increased the amounts of steady-state mRNA by posttranscriptional superinduction. It appeared, however, that new nuclear protein synthesis was required for maximal transcriptional stimulation by phorbol esters. Thus, changing cellular regulatory mechanisms influenced human retrovirus expression during human embryonic cell differentiation

  4. Oncogenic transformation by the tax gene of human T-cell leukemia virus type I in vitro

    International Nuclear Information System (INIS)

    Human T-cell leukemia virus type I (HTLV-I) is a causative agent of adult T-cell leukemia (ATL). To elucidate the role of HTLV-I in leukemogenesis, the authors examined the biological activity of a defective HTLV-I provirus with the env-pX 3' long terminal repeat region cloned from leukemic cells of an ATL patient. Transfection experiments showed growth stimulation of NIH 3T3 cells--growing beyond the saturation density and growing in soft agar. Since the pX sequence is known to encode three proteins, Tax, Rex, and p21x, the biological activity of each pX gene was examined separately. The growth-stimulating activity was induced only by the tax gene in NIH 3T3 cells and Rat-1 cells. Furthermore, the tax gene induced tumorigenicity in nude mice when introduced into Rat-1 cells. Thus, a transcriptional transactivator gene of HTLV-I, tax, is clearly identified as a viral oncogene without a cellular homolog. The transforming activity of tax, possibly via a transcriptional deregulation of cell growth control, may play an important role in leukemogenesis of ATL in addition to its aberrant stimulation of the interleukin 2 system

  5. An enhancer variant of Moloney murine leukemia virus defective in leukemogenesis does not generate detectable mink cell focus-inducing virus in vivo

    OpenAIRE

    1991-01-01

    Moloney murine leukemia virus (Mo-MuLV) induces T-cell lymphoma when inoculated into neonatal mice. This is a multistep process. Early events observed in infected mice include generalized hematopoietic hyperplasia in the spleen and appearance of mink cell focus-inducing (MCF) recombinants; end-stage tumors are characterized by insertional proviral activation of protooncogenes. We previously showed that an Mo-MuLV enhancer variant, Mo+PyF101 Mo-MuLV, has greatly reduced leukemogenicity and is ...

  6. Human T-cell leukemia virus type 1 tax attenuates the ATM-mediated cellular DNA damage response.

    Science.gov (United States)

    Chandhasin, Chandtip; Ducu, Razvan I; Berkovich, Elijahu; Kastan, Michael B; Marriott, Susan J

    2008-07-01

    Genomic instability, a hallmark of leukemic cells, is associated with malfunctioning cellular responses to DNA damage caused by defective cell cycle checkpoints and/or DNA repair. Adult T-cell leukemia, which can result from infection with human T-cell leukemia virus type 1 (HTLV-1), is associated with extensive genomic instability that has been attributed to the viral oncoprotein Tax. How Tax influences cellular responses to DNA damage to mediate genomic instability, however, remains unclear. Therefore, we investigated the effect of Tax on cellular pathways involved in recognition and repair of DNA double-strand breaks. Premature attenuation of ATM kinase activity and reduced association of MDC1 with repair foci were observed in Tax-expressing cells. Following ionizing radiation-induced S-phase checkpoint activation, Tax-expressing cells progressed more rapidly than non-Tax-expressing cells toward DNA replication. These results demonstrate that Tax expression may allow premature DNA replication in the presence of genomic lesions. Attempts to replicate in the presence of these lesions would result in gradual accumulation of mutations, leading to genome instability and cellular transformation. PMID:18434398

  7. Comparison of immunofluorescence, particle agglutination, and enzyme immunoassays for detection of human T-cell leukemia virus type I antibody in African sera.

    OpenAIRE

    Verdier, M.; Denis, F.; Leonard, G; A. Sangare; Patillaud, S; Prince-David, M.; M Essex

    1990-01-01

    The effectiveness of four screening tests for detecting antibody to human T-cell leukemia virus type I (HTLV-I) was determined by using 2,700 African serum specimens. The tests studied were indirect immunofluorescence, particle agglutination from Fujirebio, and two enzyme immunoassays, one from Abbott Laboratories that used virus lysate from HUT 102 cells and the other from Cambridge BioScience Corp. that used an env recombinant protein. Positive and doubtful sera were confirmed by Western im...

  8. Human T cell leukemia virus-I (HTLV-I) Tax-mediated apoptosis in activated T cells requires an enhanced intracellular prooxidant state

    OpenAIRE

    Los, Marek Jan; Khazaie, K; Schulze-Osthoff, Klaus; Baeuerle, P A; Schirrmacher, V.; Chlichlia, K.

    1998-01-01

    We have shown that an estradiol-dependent activation of human T cell leukemia virus-I Tax leads to the inhibition of cell proliferation and to the induction of apoptosis, The present study demonstrates that a hormone-dependent activation of Tax promotes an enhanced prooxidant state in stably transfected Jurkat cells as measured by changes in the intracellular levels of glutathione and H2O2; these changes are followed by apoptotic cell death. Additional stimulation of the CD3/TCR pathway enhan...

  9. Genomic instability driven by the human T-cell leukemia virus type I (HTLV-I) oncoprotein, Tax.

    Science.gov (United States)

    Lemoine, Francene J; Marriott, Susan J

    2002-10-17

    The importance of maintaining genomic stability is evidenced by the fact that transformed cells often contain a variety of chromosomal abnormalities such as euploidy, translocations, and inversions. Gene amplification is a well-characterized hallmark of genomic instability thought to result from recombination events following the formation of double-strand, chromosomal breaks. Therefore, gene amplification frequency serves as an indicator of genomic stability. The PALA assay is designed to measure directly the frequency with which a specific gene, CAD, is amplified within a cell's genome. We have used the PALA assay to analyse the effects of the human T-cell leukemia virus type I (HTLV-I) oncoprotein, Tax, on genomic amplification. We demonstrate that Tax-expressing cells are five-times more likely to undergo gene amplification than control cells. Additionally, we show that Tax alters the ability of cells to undergo the typical PALA-mediated G(1) phase cell cycle arrest, thereby allowing cells to replicate DNA in the absence of appropriate nucleotide pools. This effect is likely the mechanism by which Tax induces gene amplification. These data suggest that HTLV-I Tax alters the genomic stability of cells, an effect that may play an important role in Tax-mediated, HTLV-I associated cellular transformation. PMID:12370813

  10. Vaccination against δ-retroviruses: the bovine leukemia virus paradigm.

    Science.gov (United States)

    Gutiérrez, Gerónimo; Rodríguez, Sabrina M; de Brogniez, Alix; Gillet, Nicolas; Golime, Ramarao; Burny, Arsène; Jaworski, Juan-Pablo; Alvarez, Irene; Vagnoni, Lucas; Trono, Karina; Willems, Luc

    2014-06-01

    Bovine leukemia virus (BLV) and human T-lymphotropic virus type 1 (HTLV-1) are closely related d-retroviruses that induce hematological diseases. HTLV-1 infects about 15 million people worldwide, mainly in subtropical areas. HTLV-1 induces a wide spectrum of diseases (e.g., HTLV-associated myelopathy/tropical spastic paraparesis) and leukemia/lymphoma (adult T-cell leukemia). Bovine leukemia virus is a major pathogen of cattle, causing important economic losses due to a reduction in production, export limitations and lymphoma-associated death. In the absence of satisfactory treatment for these diseases and besides the prevention of transmission, the best option to reduce the prevalence of d-retroviruses is vaccination. Here, we provide an overview of the different vaccination strategies in the BLV model and outline key parameters required for vaccine efficacy. PMID:24956179

  11. Vaccination against δ-Retroviruses: The Bovine Leukemia Virus Paradigm

    Directory of Open Access Journals (Sweden)

    Gerónimo Gutiérrez

    2014-06-01

    Full Text Available Bovine leukemia virus (BLV and human T-lymphotropic virus type 1 (HTLV-1 are closely related d-retroviruses that induce hematological diseases. HTLV-1 infects about 15 million people worldwide, mainly in subtropical areas. HTLV-1 induces a wide spectrum of diseases (e.g., HTLV-associated myelopathy/tropical spastic paraparesis and leukemia/lymphoma (adult T-cell leukemia. Bovine leukemia virus is a major pathogen of cattle, causing important economic losses due to a reduction in production, export limitations and lymphoma-associated death. In the absence of satisfactory treatment for these diseases and besides the prevention of transmission, the best option to reduce the prevalence of d-retroviruses is vaccination. Here, we provide an overview of the different vaccination strategies in the BLV model and outline key parameters required for vaccine efficacy.

  12. Immunogenetics and the Pathological Mechanisms of Human T-Cell Leukemia Virus Type 1- (HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP

    Directory of Open Access Journals (Sweden)

    Mineki Saito

    2010-01-01

    Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 is a replication-competent human retrovirus associated with two distinct types of disease only in a minority of infected individuals: the malignancy known as adult T-cell leukemia (ATL and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence suggests that complex virus-host interactions play an important role in determining the risk of HAM/TSP. This review focuses on the role of the immune response in controlling or limiting viral persistence in HAM/TSP patients, and the reason why some HTLV-1-infected people develop HAM/TSP whereas the majority remains asymptomatic carriers of the virus.

  13. Induction of Lactoferrin Gene Expression in Myeloid or Mammary Gland Cells by Human T-Cell Leukemia Virus Type 1 (HTLV-1) Tax: Implications for Milk-Borne Transmission of HTLV-1

    OpenAIRE

    Moriuchi, Masako; Moriuchi, Hiroyuki

    2006-01-01

    Human T-cell leukemia virus type 1 (HTLV-1), the causative agent of adult T-cell leukemia, is transmitted vertically via breastfeeding. We have previously demonstrated that lactoferrin, a major milk protein, enhances HTLV-1 replication, at least in part by upregulating the HTLV-1 long terminal repeat promoter. We now report that HTLV-1 infection can induce lactoferrin gene expression. Coculture with HTLV-1-infected MT-2 cells increased the levels of lactoferrin mRNA in myeloid-differentiated ...

  14. Chimeras of receptors for gibbon ape leukemia virus/feline leukemia virus B and amphotropic murine leukemia virus reveal different modes of receptor recognition by retrovirus

    DEFF Research Database (Denmark)

    Pedersen, Lene; Johann, Stephen V; van Zeijl, Marja;

    1995-01-01

    Glvr1 encodes the human receptor for gibbon ape leukemia virus (GALV) and feline leukemia virus subgroup B (FeLV-B), while the related gene Glvr2 encodes the human receptor for amphotropic murine leukemia viruses (A-MLVs). The two proteins are 62% identical in their amino acid sequences and are...

  15. Use of human antigen presenting cell gene array profiling to examine the effect of human T-cell leukemia virus type 1 Tax on primary human dendritic cells.

    Science.gov (United States)

    Ahuja, Jaya; Kampani, Karan; Datta, Suman; Wigdahl, Brian; Flaig, Katherine E; Jain, Pooja

    2006-02-01

    Human T-cell leukemia virus type 1 (HTLV-1) is etiologically linked to adult T-cell leukemia and a progressive demyelinating disorder termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). One of the most striking features of the immune response in HAM/TSP centers on the expansion of HTLV-1-specific CD8(+) cytotoxic T lymphocyte (CTL) compartment in the peripheral blood and cerebrospinal fluid. More than 90% of the HTLV-1-specific CTLs are directed against the viral Tax (11-19) peptide implying that Tax is available for immune recognition by antigen presenting cells, such as dendritic cells (DCs). DCs obtained from HAM/TSP patients have been shown to be infected with HTLV-1 and exhibit rapid maturation. Therefore, we hypothesized that presentation of Tax peptides by activated DCs to naIve CD8(+) T cells may play an important role in the induction of a Tax-specific CTL response and neurologic dysfunction. In this study, a pathway-specific antigen presenting cell gene array was used to study transcriptional changes induced by exposure of monocyte-derived DCs to extracellular HTLV-1 Tax protein. Approximately 100 genes were differentially expressed including genes encoding toll-like receptors, cell surface receptors, proteins involved in antigen uptake and presentation and adhesion molecules. The differential regulation of chemokines and cytokines characteristic of functional DC activation was also observed by the gene array analyses. Furthermore, the expression pattern of signal transduction genes was also significantly altered. These results have suggested that Tax-mediated DC gene regulation might play a critical role in cellular activation and the mechanisms resulting in HTLV-1-induced disease. PMID:16595374

  16. Clastogenic effect of the human T-cell leukemia virus type I Tax oncoprotein correlates with unstabilized DNA breaks.

    Science.gov (United States)

    Majone, F; Jeang, K T

    2000-10-20

    Expression of the human T-cell leukemia virus type I (HTLV-I) Tax oncoprotein rapidly engenders DNA damage as reflected in a significant increase of micronuclei (MN) in cells. To understand better this phenomenon, we have investigated the DNA content of MN induced by Tax. Using an approach that we termed FISHI, fluorescent in situ hybridization and incorporation, we attempted to characterize MN with centric or acentric DNA fragments for the presence or absence of free 3'-OH ends. Free 3'-OH ends were defined as those ends accessible to in situ addition of digoxigenin-dUTP using terminal deoxynucleotidyl transferase. MN were also assessed for centromeric sequences using standard fluorescent in situ hybridization (FISH). Combining these results, we determined that Tax oncoprotein increased the frequency of MN containing centric DNA with free 3'-OH and decreased the frequency of MN containing DNA fragments that had incorporation-inaccessible 3'-ends. Recently, it has been suggested that intracellular DNA breaks without detectable 3'-OH ends are stabilized by the protective addition of telomeric caps, while breaks with freely detectable 3'-OH are uncapped and are labile to degradation, incomplete replication, and loss during cell division. Accordingly, based on increased detection of free 3'-OH-containing DNA fragments, we concluded that HTLV-I Tax interferes with protective cellular mechanism(s) used normally for stabilizing DNA breaks. PMID:10969065

  17. Some lymphoid cell lines transformed by Abelson murine leukemia virus lack a major 36,000-dalton tyrosine protein kinase substrate.

    OpenAIRE

    Sefton, B M; Hunter, T; Cooper, J. A.

    1983-01-01

    Fibroblasts transformed by Abelson murine leukemia virus differ from normal fibroblasts in that they contain several cellular proteins, including one of 29 and one of 36 kilodaltons, which are phosphorylated at tyrosine residues. Since it has been shown before that these proteins also become phosphorylated at tyrosine after transformation of fibroblasts by a number of other retroviruses, their phosphorylation may play an important role in the transformation of these cells. In contrast, the 36...

  18. Integration of murine leukemia virus DNA depends on mitosis.

    OpenAIRE

    Roe, T.; Reynolds, T. C.; Yu, G.; Brown, P O

    1993-01-01

    In synchronized rat or mouse cells infected with Moloney murine leukemia virus (MLV), integration of viral DNA and production of viral proteins occur only after the cells traverse mitosis. Integration is blocked when cells are prevented from progressing through mitosis. Viral nucleoprotein complexes isolated from arrested cells contain full-length viral DNA and can integrate this viral DNA in vitro, showing that the block to integration in arrested cells is not due to a lack of mature integra...

  19. Downregulation of proapoptotic Bim augments IL-2-independent T-cell transformation by human T-cell leukemia virus type-1 Tax

    International Nuclear Information System (INIS)

    Human T-cell leukemia virus type 1 (HTLV-1), an etiological agent of adult T-cell leukemia, immortalizes and transforms primary human T cells in vitro in both an interleukin (IL)-2-dependent and IL-2-independent manner. Expression of the HTLV-1 oncoprotein Tax transforms the growth of the mouse T-cell line CTLL-2 from being IL-2-dependent to IL-2-independent. Withdrawal of IL-2 from normal activated T cells induces apoptosis, which is mediated through the inducible expression of several proapoptotic proteins, including Bim. In this study, we found that Tax protects IL-2-depleted T cells against Bim-induced apoptosis. Withdrawal of IL-2 from CTLL-2 cells induced a prominent increase in the level of Bim protein in CTLL-2 cells, but not in Tax-transformed CTLL-2 cells. This inhibition of Bim in Tax-transformed CTLL-2 cells was mediated by two mechanisms: downregulation of Bim mRNA and posttranscriptional reduction of Bim protein. Transient expression of Tax in CTLL-2 cells also inhibited IL-2 depletion–induced expression of Bim, however, this decrease in Bim protein expression was not due to downregulation of Bim mRNA, thus indicating that Bim mRNA downregulation in Tax-transformed CTLL-2 occurs only after long-term expression of Tax. Transient expression of Tax in CTLL-2 cells also induced Erk activation, however, this was not involved in the reduction of Bim protein. Knockdown of Bim expression in CTLL-2 cells augmented Tax-induced IL-2-independent transformation. HTLV-1 infection of human T cells also reduced their levels of Bim protein, and restoring Bim expression in HTLV-1-infected cells reduced their proliferation by inducing apoptosis. Taken together, these results indicate that Tax-induced downregulation of Bim in HTLV-1-infected T cells promotes their IL-2-independent growth, thereby supporting the persistence of HTLV-1 infection in vivo

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

    International Nuclear Information System (INIS)

    This study investigates the role of the proviral transcriptional enhancer for B-lymphoma induction by exogenous Akv murine leukemia virus. Infection of newborn inbred NMRI mice with Akv induced 35% plasma cell proliferations (PCPs) (consistent with plasmacytoma), 33% diffuse large B-cell lymphomas, 25% follicular B-cell lymphomas and few splenic marginal zone and small B-cell lymphomas. Deleting one copy of the 99-bp proviral enhancer sequence still allowed induction of multiple B-cell tumor types, although PCPs dominated (77%). Additional mutation of binding sites for the glucocorticoid receptor, Ets, Runx, or basic helix-loop-helix transcription factors in the proviral U3 region, however, shifted disease induction to almost exclusively PCPs, but had no major influence on tumor latency periods. Southern analysis of immunoglobulin rearrangements and ecotropic provirus integration patterns showed that many of the tumors/cell proliferations induced by each virus were polyclonal. Our results indicate that enhancer mutations weaken the ability of Akv to induce mature B-cell lymphomas prior to the plasma cell stage, whereas development of plasma cell proliferations is less dependent of viral enhancer strength

  1. Human T cell lymphotropic virus type I genomic expression and impact on intracellular signaling pathways during neurodegenerative disease and leukemia.

    Science.gov (United States)

    Yao, J; Wigdahl, B

    2000-01-01

    HTLV-I has been identified as the etiologic agent of neoplasia within the human peripheral blood T lymphocyte population, and a progressive neurologic disorder based primarily within the central nervous system. We have examined the role of HTLV-I in these two distinctly different clinical syndromes by examining the life cycle of the virus, with emphasis on the regulation of viral gene expression within relevant target cell populations. In particular, we have examined the impact of specific viral gene products, particularly Tax, on cellular metabolic function. Tax is a highly promiscuous and pleiotropic viral oncoprotein, and is the most important factor contributing to the initial stages of viral-mediated transformation of T cells after HTLV-I infection. Tax, which weakly binds to Tax response element 1 (TRE-1) in the viral long terminal repeat (LTR), can dramatically trans-activate viral gene expression by interacting with cellular transcription factors, such as activated transcription factors and cyclic AMP response element binding proteins (ATF/CREB), CREB binding protein (CBP/p300), and factors involved with the basic transcription apparatus. At the same time, Tax alters cellular gene expression by directly or indirectly interacting with a variety of cellular transcription factors, cell cycle control elements, and cellular signal transduction molecules ultimately resulting in dysregulated cell proliferation. The mechanisms associated with HTLV-I infection, leading to tropical spastic paraparesis (TSP) are not as clearly resolved. Possible explanations of viral-induced neurologic disease range from central nervous system (CNS) damage caused by direct viral invasion of the CNS to bystander CNS damage caused by the immune response to HTLV-I infection. It is interesting to note that it is very rare for an HTLV-I infected individual to develop both adult T cell leukemia (ATL) and TSP in his/her life time, suggesting that the mechanisms governing development of these

  2. Plasma cell leukemia

    OpenAIRE

    Gertz, Moria A.; Buadi, Francis K.

    2010-01-01

    Plasma cell leukemia (PCL) is a rare, yet aggressive plasma cell (PC) neoplasm, variant of multiple myeloma (MM), characterized by high levels of PCs circulating in the peripheral blood. PCL can either originate de novo (primary PCL) or as a secondary leukemic transformation of MM (secondary PCL). Presenting signs and symptoms are similar to those seen in MM such as renal insufficiency, hypercalcemia, lytic bone lesions, anemia, and thrombocytopenia, but can also include hepatomegaly and sple...

  3. Economics of bovine leukemia virus infection.

    Science.gov (United States)

    Pelzer, K D

    1997-03-01

    A herd infected with bovine leukemia virus suffers a direct economic loss due to clinical lymphosarcoma. A major indirect cost associated with infection is restriction of the sale of animals and germplasma to foreign markets. Reports on the economic effects of infection on production have been variable and are reviewed in this article. In order to develop cost-effective bovine leukemia virus control programs, costs associated with the disease, the cost of prevention, and expected economic returns from a program need to be considered. PMID:9071750

  4. Plasma cell leukemia

    DEFF Research Database (Denmark)

    Fernández de Larrea, C; Kyle, R A; Durie, B G M;

    2013-01-01

    -pathological entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (≥ 20%) and absolute number (≥ 2 × 10(9)/l) of plasma cells in the peripheral blood. It is proposed that the thresholds for......Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic...

  5. Tax fingerprint in adult T-cell leukemia.

    Science.gov (United States)

    Bazarbachi, Ali

    2016-04-01

    In this issue of Blood, Fujikawa et al demonstrate that the human T-cell leukemia virus type 1 (HTLV-1) oncoprotein Tax induces an epigenetic-dependent global modification of host gene expression in adult T-cell leukemia-lymphoma (ATL). Hence, the fingerprint of Tax is all over ATL and this may be used for finally capturing ATL. PMID:27056993

  6. ESCRT Requirements for Murine Leukemia Virus Release

    Science.gov (United States)

    Bartusch, Christina; Prange, Reinhild

    2016-01-01

    The Murine Leukemia Virus (MLV) is a gammaretrovirus that hijack host components of the endosomal sorting complex required for transport (ESCRT) for budding. To determine the minimal requirements for ESCRT factors in MLV viral and viral-like particles (VLP) release, an siRNA knockdown screen of ESCRT(-associated) proteins was performed in MLV-producing human cells. We found that MLV VLPs and virions primarily engage the ESCRT-I factor Tsg101 and marginally the ESCRT-associated adaptors Nedd4-1 and Alix to enter the ESCRT pathway. Conversely, the inactivation of ESCRT-II had no impact on VLP and virion egress. By analyzing the effects of individual ESCRT-III knockdowns, VLP and virion release was profoundly inhibited in CHMP2A- and CHMP4B-knockdown cells. In contrast, neither the CHMP2B and CHMP4A isoforms nor CHMP3, CHMP5, and CHMP6 were found to be essential. In case of CHMP1, we unexpectedly observed that the CHMP1A isoform was specifically required for virus budding, but dispensable for VLP release. Hence, MLV utilizes only a subset of ESCRT factors, and viral and viral-like particles differ in ESCRT-III factor requirements. PMID:27096867

  7. Regulating the leukemia stem cell

    OpenAIRE

    Cleary, Michael L.

    2009-01-01

    Leukemia stem cells (LSCs) are responsible for sustaining and propagating malignant disease, and, as such, are promising targets for therapy. Studies of human LSCs have served an important role in defining the major tenets of the cancer stem cell model, which center on the frequencies of cancer stem cells, their potential hierarchical organization, and their degree of maturation. LSCs in acute myeloid leukemia (AML) have recently been studied using mouse syngeneic models of leukemia induced b...

  8. Transcriptional activation of homologous viral long terminal repeats by the human immunodeficiency virus type 1 or the human T-cell leukemia virus type I tat proteins occurs in the absence of de novo protein synthesis.

    OpenAIRE

    Jeang, K T; Shank, P R; Kumar, A

    1988-01-01

    The genomes of human retroviruses [human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus (HTLV-I)] encode positive trans-activator proteins, named tat. In the presence of tat, the transcriptional activity of the homologous HIV-1 or HTLV-I long terminal repeat (LTR) promoter is markedly increased. We have constructed mammalian cell lines that contain stably integrated copies of a HIV-1 or a HTLV-I LTR-chloramphenicol acetyltransferase (CAT) gene. When presynthesized HIV-1...

  9. The Icsbp locus is a common proviral insertion site in mature B-cell lymphomas/plasmacytomas induced by exogenous murine leukemia virus

    International Nuclear Information System (INIS)

    ICSBP (interferon consensus sequence binding protein)/IRF8 (interferon regulatory factor 8) is an interferon gamma-inducible transcription factor expressed predominantly in hematopoietic cells, and down-regulation of this factor has been observed in chronic myelogenous leukemia and acute myeloid leukemia in man. By screening about 1200 murine leukemia virus (MLV)-induced lymphomas, we found proviral insertions at the Icsbp locus in 14 tumors, 13 of which were mature B-cell lymphomas or plasmacytomas. Only one was a T-cell lymphoma, although such tumors constituted about half of the samples screened. This indicates that the Icsbp locus can play a specific role in the development of mature B-lineage malignancies. Two proviral insertions in the last Icsbp exon were found to act by a poly(A)-insertion mechanism. The remaining insertions were found within or outside Icsbp. Since our results showed expression of Icsbp RNA and protein in all end-stage tumor samples, a simple tumor suppressor function of ICSBP is not likely. Interestingly, proviral insertions at Icsbp have not been reported from previous extensive screenings of mature B-cell lymphomas induced by endogenous MLVs. We propose that ICSBP might be involved in an early modulation of an immune response to exogenous MLVs that might also play a role in proliferation of the mature B-cell lymphomas

  10. Appearance of murine leukemia virus in NIH Swiss mice with radiation-induced leukemia

    International Nuclear Information System (INIS)

    In the NIH Swiss mouse strain, a low leukemic strain, thymic lymphomas were efficiently induced by fractionated X-irradiation. However, neither XC-plaqueforming virus nor mink S+L- cell focus-inducing virus were found in either leukemic or normal mice. A search for murine leukemia virus-related components was carried out in NIH Swiss mice with radiation-induced leukemias by measurement of viral specific RDDP activity and radioimmunoassay for p30. RDDP activities in thymomas from leukemic mice were sign ificantly higher than thymuses from normal mice. RDDP-containing particles obtaind from those thymomas showed a buoyant density of 1.16(g/m1). Radioimmunoassay studies showed that thymomas and enlarged spleens of leukemic mice contained much higher amounts of p30 than those of normal mice, but there was no difference in the p30 level of bone marrow, u terus or liver between normal and leukemic mice. The possible role in leukemogeneis of these murine leukemia virus-like particles appearing in mice with radiation-induced leukemia is discussed. (author)

  11. Leukemia Stem Cells and Human Acute Lymphoblastic Leukemia

    OpenAIRE

    Bernt, Kathrin M.; Armstrong, Scott A.

    2009-01-01

    Leukemias and other cancers have been proposed to contain a subpopulation of cells that display characteristics of stem cells, and which maintain tumor growth. That most anti-cancer therapy is directed against the bulk of the tumor, and possibly spares the cancer stem cells, may lie at the heart of treatment failures with conventional modalities. Leukemia stem cells are fairly well described for acute myeloid leukemia (AML), but their existence and relevance for acute lymphoblastic leukemia (...

  12. The role of cyclin D2 and p21/waf1 in human T-cell leukemia virus type 1 infected cells

    Directory of Open Access Journals (Sweden)

    Pumfery Anne

    2004-04-01

    Full Text Available Abstract Background The human T-cell leukemia virus type 1 (HTLV-1 Tax protein indirectly influences transcriptional activation, signal transduction, cell cycle control, and apoptosis. The function of Tax primarily relies on protein-protein interactions. We have previously shown that Tax upregulates the cell cycle checkpoint proteins p21/waf1 and cyclin D2. Here we describe the consequences of upregulating these G1/S checkpoint regulators in HTLV-1 infected cells. Results To further decipher any physical and functional interactions between cyclin D2 and p21/waf1, we used a series of biochemical assays from HTLV-1 infected and uninfected cells. Immunoprecipitations from HTLV-1 infected cells showed p21/waf1 in a stable complex with cyclin D2/cdk4. This complex is active as it phosphorylates the Rb protein in kinase assays. Confocal fluorescent microscopy indicated that p21/waf1 and cyclin D2 colocalize in HTLV-1 infected, but not in uninfected cells. Furthermore, in vitro kinase assays using purified proteins demonstrated that the addition of p21/waf1 to cyclin D2/cdk4 increased the kinase activity of cdk4. Conclusion These data suggest that the p21/cyclin D2/cdk4 complex is not an inhibitory complex and that p21/waf1 could potentially function as an assembly factor for the cyclin D2/cdk4 complex in HTLV-1 infected cells. A by-product of this assembly with cyclin D2/cdk4 is the sequestration of p21/waf1 away from the cyclin E/cdk2 complex, allowing this active cyclin-cdk complex to phosphorylate Rb pocket proteins efficiently and push cells through the G1/S checkpoint. These two distinct functional and physical activities of p21/waf1 suggest that RNA tumor viruses manipulate the G1/S checkpoint by deregulating cyclin and cdk complexes.

  13. Human T cell leukemia/lymphoma virus I infection and subsequent cloning of normal human B cells. Direct responsiveness of cloned cells to recombinant interleukin 2 by differentiation in the absence of enhanced proliferation

    OpenAIRE

    1985-01-01

    A human T cell leukemia/lymphoma virus (HTLV)-I-infected B cell clone expressed Tac antigen on its cell surface and responded to recombinant interleukin 2 (IL-2) by increased production of IgM without any increase in proliferation. Anti-Tac antibody completely inhibited the IL-2-induced differentiation of this HTLV-I-infected B cell clone. This study demonstrates that HTLV-I can directly infect normal mature human B cells, and that the Tac antigen, which may be induced by infection with HTLV-...

  14. Friend leukemia virus transformed cells exposed to microgravity in the presence of DMSO (7-IML-1)

    Science.gov (United States)

    Cogoli, Augusto

    1992-01-01

    The purpose of this experiment is to study the adaptation of living cells to microgravity. The in vitro transformation of Friend cells by Dimethylsufoxide (DMSO) is a good model for the study of cell differentiation and protein biosynthesis. Cultures of cells will be prepared shortly before launch. Once in space, transformation will be induced by injection of DMSO. One set of cultures will be chemically fixed with glutaraldehyde for electron microscope investigations; another set will be preserved for determining the amount of hemogloben produced and the extent of cell proliferation.

  15. Failure in activation of the canonical NF-κB pathway by human T-cell leukemia virus type 1 Tax in non-hematopoietic cell lines

    International Nuclear Information System (INIS)

    Human T-cell leukemia virus type 1 (HTLV-1) Tax (Tax1) plays crucial roles in leukemogenesis in part through activation of NF-κB. In this study, we demonstrated that Tax1 activated an NF-κB binding (gpκB) site of the gp34/OX40 ligand gene in a cell type-dependent manner. Our examination showed that the gpκΒ site and authentic NF-κB (IgκB) site were activated by Tax1 in hematopoietic cell lines. Non-hematopoietic cell lines including hepatoma and fibroblast cell lines were not permissive to Tax1-mediated activation of the gpκB site, while the IgκB site was activated in those cells in association with binding of RelB. However RelA binding was not observed in the gpκB and IgκB sites. Our results suggest that HTLV-1 Tax1 fails to activate the canonical pathway of NF-κB in non-hematopoietic cell lines. Cell type-dependent activation of NF-κB by Tax1 could be associated with pathogenesis by HTLV-1 infection. - Highlights: • HTLV-1 Tax1 does not activate RelA of NF-κB in non-hematopoietic cell lines. • Tax1 activates the NF-κB non-canonical pathway in non-hematopoietic cell lines. • Tax1 does not induce RelA nuclear translocation in those cell lines, unlike TNFα. • The OX40L promoter κB site is activated by ectopic, but not endogenous, RelA

  16. 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

  17. Expression of the protein product of the mouse mammary tumor virus long terminal repeat gene in phorbol ester-treated mouse T-cell-leukemia cells

    International Nuclear Information System (INIS)

    Exposure of C57BL/6 mouse EL-4 T-cell leukemia cells to phorbol ester (12-O-tetradecanoylphorbol-13-acetate) (TPA) induced the synthesis of protein products encoded by the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) region. Analysis of TPA-treated EL-4 cells with antiserum raised against a synthetic peptide predicted by the MMTV LTR open reading frame sequence detected a polypeptide migrating in gels with an apparent molecular weight of 37,000 M/sub r/, as well as three less prominent proteins with apparent molecular weights of 31,000, 34,000, and 39,000. Tryptic peptide analysis established the identity of the immunoprecipitated cellular proteins with the LTR proteins obtained from in vitro translation of MMTV genomic RNA. All four proteins were glycosylated and were derived from one initial nonglycosylated translation product of 21,000 M/sub r/. At least 10 acquired MMTV proviruses are present in the EL-4 genome, and examination of the degree of proviral methylation revealed extensive demethylation. However, no qualitative differences in the state of proviral methylation were apparent between TPA-treated and untreated cells

  18. Dynamics of perinatal bovine leukemia virus infection

    OpenAIRE

    Gutiérrez, Gerónimo; Alvarez, Irene; Merlini, Ramiro; Rondelli, Flavia; Trono, Karina

    2014-01-01

    Background Bovine leukemia virus (BLV) is highly endemic in many countries, including Argentina. As prevention of the spread from infected animals is of primary importance in breaking the cycle of BLV transmission, it is important to know the pathophysiology of BLV infection in young animals, as they are the main source of animal movement. In this work, we determined the proviral load and antibody titers of infected newborn calves from birth to first parturition (36 months). Results All calve...

  19. Delayed type hypersensitivity responses to radiation leukemia virus variants

    International Nuclear Information System (INIS)

    DTH responses were evaluated in different strains of mice shown to be resistant or sensitive to leukemogenesis by the radiation leukemia virus variants A-RadLV and D-RadLV. A significant response was observed only in the H-2 complex-linked resistant haplotypes to RadLV leukemogenesis. The DTH response could be transferred by immune cells of mice resistant to the appropriate RadLV variant. Thus, an inverse relationship between the leukemogenic activity of the virus and its immunization ability expressed by DTH response was demonstrated in different mouse strains

  20. B-cell-specific Moloney murine leukemia virus integration site 1: potential stratification factor and therapeutic target for epithelial ovarian cancer.

    Science.gov (United States)

    Zhao, Qianying; Gui, Ting; Qian, Qiuhong; Li, Lei; Shen, Keng

    2016-01-01

    Epithelial ovarian cancer, a vexing challenge for clinical management, still lacks biomarkers for early diagnosis, precise stratification, and prognostic evaluation of patients. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1), a member of the polycomb group of proteins, engages in diverse cellular processes, including proliferation, differentiation, senescence, and stem cell renewal. In addition, BMI1, as a cancer stem-cell marker, participates in tumorigenesis through various pathways. Rewardingly, recent studies have also revealed a relationship between BMI1 expression and the clinical grade/stage, therapy response, and survival outcome in a majority of human malignancies, including epithelial ovarian cancer. Therefore, BMI1 might serve as a potential stratification factor and treatment target for epithelial ovarian cancer, pending evidence from further investigations. PMID:27578986

  1. B-cell-specific Moloney murine leukemia virus integration site 1: potential stratification factor and therapeutic target for epithelial ovarian cancer

    Science.gov (United States)

    Zhao, Qianying; Gui, Ting; Qian, Qiuhong; Li, Lei; Shen, Keng

    2016-01-01

    Epithelial ovarian cancer, a vexing challenge for clinical management, still lacks biomarkers for early diagnosis, precise stratification, and prognostic evaluation of patients. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1), a member of the polycomb group of proteins, engages in diverse cellular processes, including proliferation, differentiation, senescence, and stem cell renewal. In addition, BMI1, as a cancer stem-cell marker, participates in tumorigenesis through various pathways. Rewardingly, recent studies have also revealed a relationship between BMI1 expression and the clinical grade/stage, therapy response, and survival outcome in a majority of human malignancies, including epithelial ovarian cancer. Therefore, BMI1 might serve as a potential stratification factor and treatment target for epithelial ovarian cancer, pending evidence from further investigations.

  2. Human T-cell leukemia virus type-1-encoded protein HBZ represses p53 function by inhibiting the acetyltransferase activity of p300/CBP and HBO1

    Science.gov (United States)

    Hoang, Kimson; Ankney, John A.; Nguyen, Stephanie T.; Rushing, Amanda W.; Polakowski, Nicholas; Miotto, Benoit; Lemasson, Isabelle

    2016-01-01

    Adult T-cell leukemia (ATL) is an often fatal malignancy caused by infection with the complex retrovirus, human T-cell Leukemia Virus, type 1 (HTLV-1). In ATL patient samples, the tumor suppressor, p53, is infrequently mutated; however, it has been shown to be inactivated by the viral protein, Tax. Here, we show that another HTLV-1 protein, HBZ, represses p53 activity. In HCT116 p53+/+ cells treated with the DNA-damaging agent, etoposide, HBZ reduced p53-mediated activation of p21/CDKN1A and GADD45A expression, which was associated with a delay in G2 phase-arrest. These effects were attributed to direct inhibition of the histone acetyltransferase (HAT) activity of p300/CBP by HBZ, causing a reduction in p53 acetylation, which has be linked to decreased p53 activity. In addition, HBZ bound to, and inhibited the HAT activity of HBO1. Although HBO1 did not acetylate p53, it acted as a coactivator for p53 at the p21/CDKN1A promoter. Therefore, through interactions with two separate HAT proteins, HBZ impairs the ability of p53 to activate transcription. This mechanism may explain how p53 activity is restricted in ATL cells that do not express Tax due to modifications of the HTLV-1 provirus, which accounts for a majority of patient samples. PMID:26625199

  3. Human T cell leukemia virus type I and neurologic disease: events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation.

    Science.gov (United States)

    Grant, Christian; Barmak, Kate; Alefantis, Timothy; Yao, Jing; Jacobson, Steven; Wigdahl, Brian

    2002-02-01

    Human T cell lymphotropic/leukemia virus type I (HTLV-I) has been identified as the causative agent of both adult T cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the exact sequence of events that occur during the early stages of infection are not known in detail, the initial route of infection may predetermine, along with host, environmental, and viral factors, the subset of target cells and/or the primary immune response encountered by HTLV-I, and whether an HTLV-I-infected individual will remain asymptomatic, develop ATL, or progress to the neuroinflammatory disease, HAM/TSP. Although a large number of studies have indicated that CD4(+) T cells represent an important target for HTLV-I infection in the peripheral blood (PB), additional evidence has accumulated over the past several years demonstrating that HTLV-I can infect several additional cellular compartments in vivo, including CD8(+) T lymphocytes, PB monocytes, dendritic cells, B lymphocytes, and resident central nervous system (CNS) astrocytes. More importantly, extensive latent viral infection of the bone marrow, including cells likely to be hematopoietic progenitor cells, has been observed in individuals with HAM/TSP as well as some asymptomatic carriers, but to a much lesser extent in individuals with ATL. Furthermore, HTLV-I(+) CD34(+) hematopoietic progenitor cells can maintain the intact proviral genome and initiate viral gene expression during the differentiation process. Introduction of HTLV-I-infected bone marrow progenitor cells into the PB, followed by genomic activation and low level viral gene expression may lead to an increase in proviral DNA load in the PB, resulting in a progressive state of immune dysregulation including the generation of a detrimental cytotoxic Tax-specific CD8(+) T cell population, anti-HTLV-I antibodies, and neurotoxic cytokines involved in disruption of myelin-producing cells and neuronal degradation

  4. Detection of HLA-D-region-associated antigens on the surface of adult T-cell leukemia virus particles by immunoelectron microscopy.

    Directory of Open Access Journals (Sweden)

    Ohtsuki,Yuji

    1984-12-01

    Full Text Available To search for lymphocyte marker antigens on the surface of human T-cell leukemia virus (HTLV, an immunoelectron microscopic study was performed on a HTLV-producing human T-cell line, MT-2, using monoclonal antibodies, such as anti-Leu-1, -Leu-2b, -Leu-3a, -Leu-5, -Leu-10 and -HLA-DR and OKIal. The reactivity of each antibody with MT-2 cells was tested by the immunoperoxidase method at the light microscopic level. OKIal, anti-HLA-DR and -Leu-10 gave positive results. At the ultrastructural level, the surface of HTLV as well as the plasma membranes of MT-2 cells were labeled with ferritin by the monoclonal antibodies OKIal, anti-HLA-DR and -Leu-10, but not by anti-Leu-1 and -Leu-3a. These findings suggest that HLA-D region -associated antigens are common antigenic determinants shared by the surface of HTLV and the plasma membranes of MT-2 cells. These antigens on the virus surface are probably picked up selectively from the plasma membranes and may play an important role in the interaction of HTLV and target T-cells.

  5. 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. ...

  6. Transient virus expression during murine leukemia induction by x-irradiation

    International Nuclear Information System (INIS)

    Most x-irradiation-induced thymomas in C57BL/6 mice are virus-free when assayed by immunofluorescence for the gs antigen (gsa) of murine leukemia virus (MuLV). Virus was induced transiently in bone marrow cells and later appeared in thymus cells. Six to 7 weeks post irradiation, thymocytes and bone marrow cells were MuLV gsa-negative and remained negative for the lifetime of most animals, whether or not they contracted overt leukemia. During the period when MuLV gsa-positive bone marrow cells were found, XC-positive syncytia-producing bone marrow cells were also found. Virus information was expressed, therefore, for a limited duration, long before any signs of leukemia in the animal were evident. MuLV gsa-positive thymocytes taken from mice 4 weeks after x-irradiation were cocultivated with a series of indicator cells. B-tropic virus, in addition to a xenotropic virus, was isolated from these cells. Ecotropic virus was not found in normal mouse thymocytes, in irradiated thymocytes a few days after termination of the X-irradiation sequence, or in most primary thymomas. All thymocytes produced only xenotropic virus in the cocultivation assays. Expression of the ecotropic virus was, therefore, transient, as assayed by immunofluorescence, XC syncytia formation, and virus isolation from MuLV gsa-positive thymus cells

  7. Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40tax protein in the human T-cell line, Jurkat.

    OpenAIRE

    Nagata, K.(Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan); Ohtani, K; Nakamura, M.; Sugamura, K

    1989-01-01

    We examined the ability of the trans-acting factor p40tax of human T-cell leukemia virus type I (HTLV-I), which is thought to be a crucial molecule in T-cell transformation by HTLV-I, to activate expression of a set of endogenous cellular genes related to T-cell proliferation. For this purpose we established a subclone (JPX-9) of Jurkat cells that was stably transfected with an expression plasmid containing the p40tax gene, whose expression is definitely dependent on heavy-metal ions. Express...

  8. Molecular characterization of RadLV (radiation leukemia virus)

    International Nuclear Information System (INIS)

    Following a course of a fractionated whole-body x-irradiation, a high percentage of C57BL/Ka mice develop thymic lymphomas. Radiation leukemia virus (RadLV) can be consistently isolated from these tumors. RadLV can induce identical lymphomas in unirradiated C57BL/Ka mice, and its role as the etiologic agent of these malignancies has been clearly documented. In order to characterize the viral genome at the molecular level, the unintegrated DNA intermediates of several RadLV isolates were prepared. Several different protocols were developed to optimize the yield and quality of restriction endonucleases, and cloned into a bacteriophage vector using recombinant DNA technology. RadLV is a general term used to describe a number of lymphomagenic viruses isolated from (1) primary radiation-induced lymphomas, (2) virus-induced lymphomas, and (3) established cell lines. The RadLV viruses replicate preferentially in the thymus and cause thymic lymphomas. Non-thymotropic, non-oncogenic, fibrotropic viruses can also be isolated from C57BL/Ka mice. Thus, a spectrum of biological activities can be seen among the C57BL/Ka mouse retroviruses. This dissertation reports the molecular cloning of three of the RadLV viruses. They are: (1) RadLV/VL3 and (2) RadLV/RL10, both lymphomagenic viruses, and (3) RadLV/RL15, a non-oncogenic isolate. The generation of restriction maps from both the cloned DNAs and the unintegrated viral DNA intermediates is described. These maps are compared with those of other C57BL/Ka murine retroviruses, and with published maps of other murine leukemia viruses

  9. Hairy Cell Leukemia Treatment Option Overview

    Science.gov (United States)

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

  10. General Information About Hairy Cell Leukemia

    Science.gov (United States)

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

  11. Identification of bovine leukemia virus tax function associated with host cell transcription, signaling, stress response and immune response pathway by microarray-based gene expression analysis

    Directory of Open Access Journals (Sweden)

    Arainga Mariluz

    2012-03-01

    Full Text Available Abstract Background Bovine leukemia virus (BLV is associated with enzootic bovine leukosis and is closely related to human T-cell leukemia virus type I. The Tax protein of BLV is a transcriptional activator of viral replication and a key contributor to oncogenic potential. We previously identified interesting mutant forms of Tax with elevated (TaxD247G or reduced (TaxS240P transactivation effects on BLV replication and propagation. However, the effects of these mutations on functions other than transcriptional activation are unknown. In this study, to identify genes that play a role in the cascade of signal events regulated by wild-type and mutant Tax proteins, we used a large-scale host cell gene-profiling approach. Results Using a microarray containing approximately 18,400 human mRNA transcripts, we found several alterations after the expression of Tax proteins in genes involved in many cellular functions such as transcription, signal transduction, cell growth, apoptosis, stress response, and immune response, indicating that Tax protein has multiple biological effects on various cellular environments. We also found that TaxD247G strongly regulated more genes involved in transcription, signal transduction, and cell growth functions, contrary to TaxS240P, which regulated fewer genes. In addition, the expression of genes related to stress response significantly increased in the presence of TaxS240P as compared to wild-type Tax and TaxD247G. By contrast, the largest group of downregulated genes was related to immune response, and the majority of these genes belonged to the interferon family. However, no significant difference in the expression level of downregulated genes was observed among the Tax proteins. Finally, the expression of important cellular factors obtained from the human microarray results were validated at the RNA and protein levels by real-time quantitative reverse transcription-polymerase chain reaction and western blotting

  12. Characterization of novel Bovine Leukemia Virus (BLV) antisense transcripts by deep sequencing reveals constitutive expression in tumors and transcriptional interaction with viral microRNAs

    OpenAIRE

    Durkin, Keith; Rosewick, Nicolas; Artesi, Maria; Hahaut, Vincent; Griebel, Philip; Arsic, Natasa; Burny, Arsène; Georges, Michel; Van den Broeke, Anne

    2016-01-01

    Background Bovine Leukemia Virus (BLV) is a deltaretrovirus closely related to the Human T cell leukemia virus-1 (HTLV-1). Cattle are the natural host of BLV where it integrates into B-cells, producing a lifelong infection. Most infected animals remain asymptomatic but following a protracted latency period about 5 % develop an aggressive leukemia/lymphoma, mirroring the disease trajectory of HTLV-1. The mechanisms by which these viruses provoke cellular transformation remain opaque. In both v...

  13. Vaccination against δ−Retroviruses: The Bovine Leukemia Virus Paradigm

    Science.gov (United States)

    Gutiérrez, Gerónimo; Rodríguez, Sabrina M.; de Brogniez, Alix; Gillet, Nicolas; Golime, Ramarao; Burny, Arsène; Jaworski, Juan-Pablo; Alvarez, Irene; Vagnoni, Lucas; Trono, Karina; Willems, Luc

    2014-01-01

    Bovine leukemia virus (BLV) and human T-lymphotropic virus type 1 (HTLV-1) are closely related δ-retroviruses that induce hematological diseases. HTLV-1 infects about 15 million people worldwide, mainly in subtropical areas. HTLV-1 induces a wide spectrum of diseases (e.g., HTLV-associated myelopathy/tropical spastic paraparesis) and leukemia/lymphoma (adult T-cell leukemia). Bovine leukemia virus is a major pathogen of cattle, causing important economic losses due to a reduction in production, export limitations and lymphoma-associated death. In the absence of satisfactory treatment for these diseases and besides the prevention of transmission, the best option to reduce the prevalence of δ-retroviruses is vaccination. Here, we provide an overview of the different vaccination strategies in the BLV model and outline key parameters required for vaccine efficacy. PMID:24956179

  14. Macropinocytosis is the Entry Mechanism of Amphotropic Murine Leukemia Virus

    DEFF Research Database (Denmark)

    Rasmussen, Izabela; Vilhardt, Frederik

    2015-01-01

    infection. Understanding how pathogens and toxins exploit or divert endocytosis pathways has advanced our understanding of membrane trafficking pathways, which benefits development of new therapeutical schemes and methods of drug delivery. We show here that Murine Leukemia Virus (A-MLV) pseudotyped with the......, or NIH-3T3 cells knocked-down for caveolin expression, was unaffected. Conversely, A-MLV infection of NIH-3T3 and HeLa cells was sensitive to amiloride analogues and actin-depolymerizing drugs that interfere with macropinocytosis. Further manipulation of the actin cytoskeleton through conditional...... amphotropic (expands the host range to many mammalian cells) envelope protein gains entry into host cells by macropinocytosis. Macropinosomes form as large, fluid-filled vacuoles (up to 10 μm) following collapse of cell surface protrusions and membrane scission. We use drugs or introduction of mutant proteins...

  15. Murine leukemia virus-derived retroviral vector has differential integration patterns in human cell lines used to produce recombinant factor VIII

    Directory of Open Access Journals (Sweden)

    Marcela Cristina Correa de Freitas

    2014-06-01

    Full Text Available OBJECTIVE: Nowadays recombinant factor VIII is produced in murine cells including in Chinese hamster ovary (CHO and baby hamster kidney cells (BHK. Previous studies, using the murine leukemia virus-derived retroviral vector pMFG-FVIII-P140K, modified two recombinant human cell lines, HepG2 and Hek293 to produce recombinant factor VIII. In order to characterize these cells, the present study aimed to analyze the integration pattern of retroviral vector pMFG-FVIII-P140K.METHODS: This study used ligation-mediated polymerase chain reaction to locate the site of viral vector integration by sequencing polymerase chain reaction products. The sequences were compared to genomic databases to characterize respective clones.RESULTS: The retroviral vector presented different and non-random profiles of integration between cells lines. A preference of integration for chromosomes 19, 17 and 11 was observed for HepG2FVIIIdB/P140K and chromosome 9 for Hek293FVIIIdB/P140K. In genomic regions such as CpG islands and transcription factor binding sites, there was no difference in the integration profiles for both cell lines. Integration in intronic regions of encoding protein genes (RefSeq genes was also observed in both cell lines. Twenty percent of integrations occurred at fragile sites in the genome of the HepG2 cell line and 17% in Hek293.CONCLUSION: The results suggest that the cell type can affect the profile of chromosomal integration of the retroviral vector used; these differences may interfere in the level of expression of recombinant proteins.

  16. Molecular Hallmarks of Adult T Cell Leukemia

    Directory of Open Access Journals (Sweden)

    MakotoYamagishi

    2012-09-01

    Full Text Available The molecular hallmarks of adult T cell leukemia (ATL comprise outstanding deregulations of signaling pathways that control the cell cycle, resistance to apoptosis, and proliferation of leukemic cells, all of which have been identified by early excellent studies. Nevertheless, we are now confronted the therapeutic difficulties of ATL that is a most aggressive T cell leukemia/lymphoma. Using next-generation strategies, emerging molecular characteristics such as specific surface markers and an additional catalog of signals affecting the fate of leukemic cells have been added to the molecular hallmarks that constitute an organizing principle for rationalizing the complexities of ATL. Although human T cell leukemia virus type 1 (HTLV-1 is undoubtedly involved in ATL leukemogenesis, most leukemic cells do not express the viral protein Tax. Instead, cellular gene expression changes dominate homeostasis disorders of infected cells and characteristics of ATL. In this review, we summarize the state of the art of ATL molecular pathology, which supports the biological properties of leukemic cells. In addition, we discuss the recent discovery of two molecular hallmarks of potential generality; an abnormal microRNA (miRNA pattern and epigenetic reprogramming, which strongly involve the imbalance of the molecular network of lymphocytes. Global analyses of ATL have revealed the functional impact of crosstalk between multifunctional pathways. Clinical and biological studies on signaling inhibitory agents have also revealed novel oncogenic drivers that can be targeted in future. ATL cells, by deregulation of such pathways and their interconnections, may become masters of their own destinies. Recognizing and understanding of the widespread molecular applicability of these concepts will increasingly affect the development of novel strategies for treating ATL.

  17. Inclusion of Moloney murine leukemia virus elements upstream of the transgene cassette in an E1-deleted adenovirus leads to an unusual genomic integration in epithelial cells

    International Nuclear Information System (INIS)

    Classically, the 5' and 3' long terminal repeats (LTRs) are considered necessary but not sufficient for retroviral integration. Recently, we reported that inclusion of these and additional elements from Moloney murine leukemia virus (MoMLV) facilitated transgene integration, without retroviral integrase, when placed in an adenoviral context (AdLTR-luc vector) (Nat. Biotech. 18 (2000), 176; Biochem. Biophys. Res. Commun. 300 (2003), 115). To help understand this nonhomologous DNA recombination event, we constructed another vector, AdELP-luc, with 2.7 kb of MoMLV elements identically placed into an E1-deleted adenovirus type 5 backbone upstream of a luciferase cDNA reporter gene. Unlike AdLTR-luc, no MoMLV elements were placed downstream of the expression cassette. AdELP-luc readily infected epithelial cells in vitro. Southern hybridizations with DNA from cloned cells showed that disruption of the MoMLV sequences occurred. One cell clone, grown in vitro without any special selection medium for 9 months, exhibited stable vector integration and luciferase activity. Importantly, both Southern hybridization and FISH analyses showed that in addition to the MoMLV elements and expression cassette, substantial adenoviral sequence downstream of the luciferase cDNA was genomically integrated. These results suggest that the 2.7 kb of MoMLV sequence included in AdELP-luc have cis-acting functions and mediates an unusual integration event

  18. Genotyping of feline leukemia virus in Mexican housecats.

    Science.gov (United States)

    Ramírez, Hugo; Autran, Marcela; García, M Martha; Carmona, M Ángel; Rodríguez, Cecilia; Martínez, H Alejandro

    2016-04-01

    Feline leukemia virus (FeLV) is a retrovirus with variable rates of infection globally. DNA was obtained from cats' peripheral blood mononuclear cells, and proviral DNA of pol and env genes was detected using PCR. Seventy-six percent of cats scored positive for FeLV using env-PCR; and 54 %, by pol-PCR. Phylogenetic analysis of both regions identified sequences that correspond to a group that includes endogenous retroviruses. They form an independent branch and, therefore, a new group of endogenous viruses. Cat gender, age, outdoor access, and cohabitation with other cats were found to be significant risk factors associated with the disease. This strongly suggests that these FeLV genotypes are widely distributed in the studied feline population in Mexico. PMID:26747244

  19. Total chemical synthesis of human T-cell leukemia virus type 1 (HTLV-1) protease via native chemical ligation: Reexamination of the functional effect of C-terminal truncation

    OpenAIRE

    Li, Changqing; Li, Xiangqun; Lu, Wuyuan

    2010-01-01

    Human T-cell leukemia virus 1 (HTLV-1) protease - a member of the aspartic acid protease family plays critical roles in the pathogenesis of the virus and is an attractive viral target for therapeutic intervention. HTLV-1 protease consists of 125 amino acid residues and functions as a homodimer stabilized in part by a four-stranded β-sheet comprising the N- and C-termini. Compared with many other viral proteases such as HIV-1 protease, HTLV-1 protease is elongated by an extra 10 amino acid res...

  20. Characterization of natural antibodies in mice to endogenous leukemia virus

    International Nuclear Information System (INIS)

    The ability of radiation to induce thymic lymphomas in susceptible mice is presumably related to its ability either to induce or activate expression of the endogenous leukemia virus or its ability to immunosuppress the host sufficiently to allow escape of the virus from host regulation, or both. Techniques to quantitatively measure changes in virus expression induced by radiation now exist. In tissue culture it has been demonstrated that radiation can induce at low but significant frequencies spontaneous expression of the virus. This suggests that a similar induction by radiation can be achieved in vivo. The relative role of the immunosuppressive effects of radiation must also be examined. The spontaneous expression of endogenous leukemia viruses induces a chronic humoral response to the virus, which may contribute to the regulation of the pathologic expression of the virus. Techniques and findings on this autogenous immune response as it relates to the immunosuppressive effects of radiation in the induction of thymic lymphomas in mice are reviewed

  1. Molecular analysis and pathogenesis of the feline aplastic anemia retrovirus, feline leukemia virus C-Sarma.

    OpenAIRE

    N. Riedel; Hoover, E. A.; Gasper, P W; Nicolson, M O; Mullins, J I

    1986-01-01

    We describe the molecular cloning of an anemogenic feline leukemia virus (FeLV), FeLV-C-Sarma, from the productively infected human rhabdomyosarcoma cell line RD(FeLV-C-S). Molecularly cloned FeLV-C-S proviral DNA yielded infectious virus (mcFeLV-C-S) after transfection of mammalian cells, and virus interference studies using transfection-derived virus demonstrated that our clone encodes FeLV belonging to the C subgroup. mcFeLV-C-S did not induce viremia in eight 8-week-old outbred specific-p...

  2. Treatment of Aggressive NK-Cell Leukemia

    DEFF Research Database (Denmark)

    Boysen, Anders Kindberg; Jensen, Paw; Johansen, Preben;

    2011-01-01

    Aggressive NK-cell leukemia is a rare malignancy with neoplastic proliferation of natural killer cells. It often presents with constitutional symptoms, a rapid declining clinical course, and a poor prognosis with a median survival of a few months. The disease is usually resistant to cytotoxic...... literature concerning treatment of aggressive NK-cell leukemia....

  3. Murine leukemia virus (MLV replication monitored with fluorescent proteins

    Directory of Open Access Journals (Sweden)

    Bittner Alexandra

    2004-12-01

    Full Text Available Abstract Background Cancer gene therapy will benefit from vectors that are able to replicate in tumor tissue and cause a bystander effect. Replication-competent murine leukemia virus (MLV has been described to have potential as cancer therapeutics, however, MLV infection does not cause a cytopathic effect in the infected cell and viral replication can only be studied by immunostaining or measurement of reverse transcriptase activity. Results We inserted the coding sequences for green fluorescent protein (GFP into the proline-rich region (PRR of the ecotropic envelope protein (Env and were able to fluorescently label MLV. This allowed us to directly monitor viral replication and attachment to target cells by flow cytometry. We used this method to study viral replication of recombinant MLVs and split viral genomes, which were generated by replacement of the MLV env gene with the red fluorescent protein (RFP and separately cloning GFP-Env into a retroviral vector. Co-transfection of both plasmids into target cells resulted in the generation of semi-replicative vectors, and the two color labeling allowed to determine the distribution of the individual genomes in the target cells and was indicative for the occurrence of recombination events. Conclusions Fluorescently labeled MLVs are excellent tools for the study of factors that influence viral replication and can be used to optimize MLV-based replication-competent viruses or vectors for gene therapy.

  4. Endogenous murine leukemia virus-encoded proteins in radiation leukemias of BALB/c mice

    International Nuclear Information System (INIS)

    To explore the role of endogenous retroviruses in radiation-induced leukemogenesis in the mouse, we have examined virus-encoded proteins in nine BALB/c leukemias by pulsechase labeling procedures and serological typing with monospecific and monoclonal antibodies. The major gag precursor protein, Pr65/sup gag/, was observed in all cases, but only three leukemias expressed detectable amounts of the glycosylated gag species, gP95/sup gag/, or its precursor, Pr75/sup gag/. No evidence was found for synthesis of gag-host fusion proteins. None of the leukemias released infectious xenotropic or dualtropic virus, but all nine expressed at least one env protein with xenotropic properties. In two instances a monoclonal antibody, 35/56, which is specific for the NuLV G/sub IX/ antigen, displayed a distinctive reactivity with this class of env protein, although this antibody is unreactive with replicating xenotropic viruses. An ecotropic/xenotropic recombinant env protein with the same 35/56 phenotype was observed in a leukemia induced by a strongly leukemogenic virus isolated from a BALB/c radiation leukemia

  5. Isolation of cDNAs for DNA-binding proteins which specifically bind to a tax-responsive enhancer element in the long terminal repeat of human T-cell leukemia virus type I.

    OpenAIRE

    Tsujimoto, A; Nyunoya, H; Morita, T; Sato, T.; Shimotohno, K

    1991-01-01

    One of the gene products of human T-cell leukemia virus type I (HTLV-I), p40tax, activates its own viral transcription in trans through tax-responsive enhancers in viral long terminal repeats. Five species of cDNA clones for proteins that bind to the tax-responsive enhancer element in HTLV-I were isolated from the Jurkat cell library. The beta-galactosidase fusion protein prepared from the lysogen of a clone specifically recognized the cyclic AMP-responsive element in HTLV-I enhancer. The nuc...

  6. Abacavir, an anti–HIV-1 drug, targets TDP1-deficient adult T cell leukemia

    OpenAIRE

    Tada, Kohei; Kobayashi, Masayuki; Takiuchi, Yoko; Iwai, Fumie; Sakamoto, Takashi; Nagata, Kayoko; Shinohara, Masanobu; Io, Katsuhiro; Shirakawa, Kotaro; Hishizawa, Masakatsu; Shindo, Keisuke; Kadowaki, Norimitsu; Hirota, Kouji; Yamamoto, Junpei; Iwai, Shigenori

    2015-01-01

    Adult T cell leukemia (ATL) is an aggressive T cell malignancy caused by human T cell leukemia virus type 1 (HTLV-1) and has a poor prognosis. We analyzed the cytotoxic effects of various nucleoside analog reverse transcriptase inhibitors (NRTIs) for HIV-1 on ATL cells and found that abacavir potently and selectively kills ATL cells. Although NRTIs have minimal genotoxicities on host cells, the therapeutic concentration of abacavir induced numerous DNA double-strand breaks (DSBs) in the chrom...

  7. Seroprevalence and correlates of human T-cell lymphoma/leukemia virus type 1 antibodies among pregnant women at the University of Nigeria Teaching Hospital, Enugu, Nigeria

    Directory of Open Access Journals (Sweden)

    Okoye AE

    2014-09-01

    Full Text Available Augustine Ejike Okoye,1 Obike Godswill Ibegbulam,2 Robinson Chukwudi Onoh,3 Paul Olisaemeka Ezeonu,3 Ngozi I Ugwu,1 Lucky Osaheni Lawani,3 Chukwudi Simon Anigbo,2 Charles E Nonyelu21Department of Haematology and Immunology, Federal Teaching Hospital, Abakaliki, 2Department of Haematology and Immunology, University of Nigeria Teaching Hospital (UNTH, Ituku-Ozalla, 3Department of Obstetrics and Gynaecology, Federal Teaching Hospital, Abakaliki, NigeriaBackground: Human T-cell lymphoma/leukemia virus (HTLV-1 is a retrovirus transmitted vertically from mother to child parenterally and sexually by infected lymphocytes.Objective: The objective of this study was to determine the seroprevalence of HTLV-1 antibodies and associated risk factors for HTLV-1 infection among pregnant women in University of Nigeria Teaching Hospital, Enugu, southeast Nigeria.Materials and methods: A cross-sectional study was carried out from July to October 2010. Two hundred pregnant women were recruited consecutively from the antenatal clinic. Five milliliters of blood was collected from each of the participants into a plain sterile bottle and allowed to clot. The serum obtained was stored at -20°C until required for analysis. The serum samples were then analyzed for antibodies to HTLV-1 using a one-step incubation double-antigen sandwich enzyme-linked immunosorbent assay kit. Participants' demographic characteristics and degree of exposure to the risk factors associated with HTLV-1 infection were captured using a questionnaire. Statistical analysis of results was done using SPSS version 17.Results: The average age of the pregnant women was 28.94 years (standard deviation 4.17. The age-group with the highest representation was those between the ages of 26 and 30 years. Thirty-six percent of the population was above 30 years old. The result of the tests showed that only one respondent, a 31-year-old pregnant woman tested positive for HTLV-1 antibodies. Therefore, the

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

    DEFF Research Database (Denmark)

    Sørensen, Karina Dalsgaard; Kunder, Sandra; Quintanilla-Martinez, Leticia; Jonna, Sorensen; Jörg, Schmidt; Pedersen, Finn Skou

    2007-01-01

    , 25% follicular B-cell lymphomas and few splenic marginal zone and small B-cell lymphomas. Deleting one copy of the 99-bp proviral enhancer sequence still allowed induction of multiple B-cell tumor types, although PCPs dominated (77%). Additional mutation of binding sites for the glucocorticoid...... receptor, Ets, Runx, or basic helix-loop-helix transcription factors in the proviral U3 region, however, shifted disease induction to almost exclusively PCPs, but had no major influence on tumor latency periods. Southern analysis of immunoglobulin rearrangements and ecotropic provirus integration patterns...... showed that many of the tumors/cell proliferations induced by each virus were polyclonal. Our results indicate that enhancer mutations weaken the ability of Akv to induce mature B-cell lymphomas prior to the plasma cell stage, whereas development of plasma cell proliferations is less dependent of viral...

  9. Discovery of drugs that possess activity against feline leukemia virus

    OpenAIRE

    Greggs, Willie M.; Clouser, Christine L.; Patterson, Steven E.; Louis M Mansky

    2012-01-01

    Feline leukemia virus (FeLV) is a gammaretrovirus that is a significant cause of neoplastic-related disorders affecting cats worldwide. Treatment options for FeLV are limited, associated with serious side effects, and can be cost-prohibitive. The development of drugs used to treat a related retrovirus, human immunodeficiency virus type 1 (HIV-1), has been rapid, leading to the approval of five drug classes. Although structural differences affect the susceptibility of gammaretroviruses to anti...

  10. Purification by DNA affinity precipitation of the cellular factors HEB1-p67 and HEB1-p94 which bind specifically to the human T-cell leukemia virus type-I 21 bp enhancer.

    OpenAIRE

    Lombard-Platet, G; Jalinot, P

    1993-01-01

    Transcription driven by the proviral promoter of the Human T-cell Leukemia Virus type I (HTLV-I) is tightly regulated by the Tax1 transactivator. This viral protein potently induces the enhancer activity of a 21 bp motif repeated three times in the promoter. We have previously shown that this induction results from the binding of Tax1 to this enhancer sequence and that this association is mediated by the cellular factor HEB1. In this paper we report the purification of this factor by chromato...

  11. Origin of envelope proteins of a leukemia virus

    International Nuclear Information System (INIS)

    The roles of avian myeloblastosis virus (AMV) and host myeloblast cells in controlling the protein composition of virus envelope and host cell membrane are being studied by examining an ATPase enzyme in the virus and cells. New culture techniques for virus producing myeloblasts have been developed. (U.S.)

  12. The proviral genome of radiation leukemia virus: Molecular cloning, nucleotide sequence of its long terminal repeat and integration in lymphoma cell DNA

    International Nuclear Information System (INIS)

    The proviral genome of a thymotropic and leukemogenic C57BL/Ka mouse retrovirus, RadLV/VL/sub 3/(T+L+), was cloned as a biologically active PstI insert in the bacterial plasmid pBR322. Its restriction map was compared to those, already known, of two nonthymotropic and nonleukemogenic viruses of the same mouse strain, the ecotropic BL/Ka(B) and the xenotropic constituent of the radiation leukemia virus complex (RadLV). Differences were observed in the pol gene and in the env gene. Moreover, the nucleotide sequence of the RadLV/VL/sub 3/(T+L+) long terminal repeat revealed the existence of two copies of a 42 bp long sequence, separated by 11 nucleotides and of which BL/Ka(B) possesses only one copy

  13. Isolation of paralysis-inducing murine leukemia viruses from Friend virus passaged in rats.

    OpenAIRE

    Kai, K; Furuta, T

    1984-01-01

    Four clones of murine leukemia viruses (PVC-111, PVC-211, PVC-321, and PVC-441) were isolated from a paralyzed Fischer rat which had been infected with rat-passaged Friend leukemia virus. PVC-211 and PVC-321 viruses induced hind leg paralysis in rats and killed them within 1 month, and PVC-441 did so within 2 months after infection, whereas PVC-111 did not within 4 months. PVC-321 and PVC-441 but not PVC-111 virus grew well in brain and spinal cord media. The viral antigens were found often i...

  14. Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40 sup tax protein in the human T-cell line, Jurkat

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Kinya; Ohtani, Kiyoshi; Nakamura, Masataka; Sugamura, Kazuo (Tohoku Univ. School of Medicine, Sendai (Japan))

    1989-08-01

    The authors examined the ability of the trans-acting factor p40{sup tax} of human T-cell leukemia virus type I (HTLV-I), which is thought to be a crucial molecule in T-cell transformation by HTLV-I, to activate expression of a set of endogenous cellular genes related to T-cell proliferation. For this purpose, they established a subclone (JPX-9) of Jurkat cells that was stably transfected with an expression plasmid containing the p40{sup tax} gene, whose expression is definitively dependent on heavy-metal ions. Expression of the interleukin-2 receptor {alpha} chain in JPX-9 cells was induced in response to the induction of p40{sup tax} expression, as has been demonstrated by others in transient transfection experiments with Jurkat cells. In addition, they found that significant enhancement of expression of the nuclear proto-oncogene c-fos was closely associated with expression of p40{sup tax}. Continuous enhancement in the level of c-fos mRNA was observed in the presence of p40{sup tax}. These results suggest that (i) in addition to the interleukin-2-interleukin-2 receptor system, cellular genes such as c-fos, which regulate normal T-cell growth, are also activated directly or indirectly by p40{sup tax} and (ii) p40{sup tax}-induced modulation of gene expression plays a crucial role in T-cell transformation by HTLV-I.

  15. Xenotropic Murine Leukemia Virus-Related Virus (XMRV) and the Safety of the Blood Supply.

    Science.gov (United States)

    Johnson, Andrew D; Cohn, Claudia S

    2016-10-01

    In 2006, a new virus, xenotropic murine leukemia virus-related virus (XMRV), was discovered in a cohort of U.S. men with prostate cancer. Soon after this initial finding, XMRV was also detected in samples from patients with chronic fatigue syndrome (CFS). The blood community, which is highly sensitive to the threat of emerging infectious diseases since the HIV/AIDS crisis, recommended indefinite deferral of all blood donors with a history of CFS. As XMRV research progressed, conflicting results emerged regarding the importance of this virus in the pathophysiology of prostate cancer and/or CFS. Molecular biologists traced the development of XMRV to a recombination event in a laboratory mouse that likely occurred circa 1993. The virus was propagated via cell lines derived from a tumor present in this mouse and spread through contamination of laboratory samples. Well-controlled experiments showed that detection of XMRV was due to contaminated samples and was not a marker of or a causal factor in prostate cancer or CFS. This paper traces the development of XMRV in the prostate and CFS scientific communities and explores the effect it had on the blood community. PMID:27358491

  16. Human APOBEC3G incorporation into murine leukemia virus particles

    International Nuclear Information System (INIS)

    The human APOBEC3G protein exhibits broad antiretroviral activity against a variety of retroviruses. It is packaged into viral particles and executes its antiviral function in the target cell. The packaging of APOBEC3G into different viral particles requires a mechanism that confers this promiscuity. Here, APOBEC3G incorporation into murine leukemia virus (MLV) was studied using retroviral vectors. APOBEC3G uptake did not require either its cytidine deaminase activity or the presence of a retroviral vector genome. Results from immunoprecipitation and co-localization studies of APOBEC3G with a MLV Gag-CFP (cyan fluorescent protein) fusion protein imply an interaction between both proteins. RNase A treatment did not inhibit the co-precipitation of Gag-CFP and APOBEC3G, suggesting that the interaction is RNA independent. Like human immunodeficiency virus (HIV) Gag, the MLV Gag precursor protein appears to interact with APOBEC3G, indicating that Gag contains conserved structures which are used to encapsidate APOBEC3G into different retroviral particles

  17. RNAi Screening of Leukemia Cells Using Electroporation.

    Science.gov (United States)

    Agarwal, Anupriya; Tyner, Jeffrey W

    2016-01-01

    RNAi-mediated screening has been an integral tool for biological discovery for the past 15 years. A variety of approaches have been employed for implementation of this technique, including pooled, depletion/enrichment screening with lentiviral shRNAs, and segregated screening of panels of individual siRNAs. The latter approach of siRNA panel screening requires efficient methods for transfection of siRNAs into the target cells. In the case of suspension leukemia cell lines and primary cells, many of the conventional transfection techniques using liposomal or calcium phosphate-mediated transfection provide very low efficiency. In this case, electroporation is the only transfection technique offering high efficiency transfection of siRNAs into the target leukemia cells. Here, we describe methods for optimization and implementation of siRNA electroporation into leukemia cell lines and primary patient specimens, and we further offer suggested electroporation settings for some commonly used leukemia cell lines. PMID:27581286

  18. Eliminating Hairy Cell Leukemia Minimal Residual Disease

    Science.gov (United States)

    In this trial, patients with hairy cell leukemia who have disease-related symptoms that require treatment will be randomly assigned to receive cladribine with either concurrent rituximab or rituximab at least 6 months after completing cladribine therapy.

  19. Plumbagin Modulates Leukemia Cell Redox Status

    Directory of Open Access Journals (Sweden)

    François Gaascht

    2014-07-01

    Full Text Available Plumbagin is a plant naphtoquinone exerting anti-cancer properties including apoptotic cell death induction and generation of reactive oxygen species (ROS. The aim of this study was to elucidate parameters explaining the differential leukemia cell sensitivity towards this compound. Among several leukemia cell lines, U937 monocytic leukemia cells appeared more sensitive to plumbagin treatment in terms of cytotoxicity and level of apoptotic cell death compared to more resistant Raji Burkitt lymphoma cells. Moreover, U937 cells exhibited a ten-fold higher ROS production compared to Raji. Neither differential incorporation, nor efflux of plumbagin was detected. Pre-treatment with thiol-containing antioxidants prevented ROS production and subsequent induction of cell death by apoptosis whereas non-thiol-containing antioxidants remained ineffective in both cellular models. We conclude that the anticancer potential of plumbagin is driven by pro-oxidant activities related to the cellular thiolstat.

  20. Analysis of the T-cell receptor repertoire of human T-cell leukemia virus type 1 (HTLV-1) Tax-specific CD8+ cytotoxic T lymphocytes from patients with HTLV-1-associated disease: evidence for oligoclonal expansion.

    Science.gov (United States)

    Utz, U; Banks, D; Jacobson, S; Biddison, W E

    1996-02-01

    Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive neurological disease characterized by marked degeneration of the spinal cord and the presence of antibodies against HTLV-1. Patients with HAM/TSP, but not asymptomatic carriers, show very high precursor frequencies of HTLV-1-specific CD8+ T cells in peripheral blood and cerebrospinal fluid, suggestive of a role of these T cells in the pathogenesis of the disease. In HLA-A2+ HAM/TSP patients, HTLV-1-specific T cells were demonstrated to be directed predominantly against one HTLV-1 epitope, namely, Tax11-19. In the present study, we analyzed HLA-A2-restricted HTLV-1 Tax11-19-specific cytotoxic T cells from three patients with HAM/TSP. An analysis of the T-cell receptor (TCR) repertoire of these cells revealed an absence of restricted variable (V) region usage. Different combinations of TCR V alpha and V beta genes were utilized between, but also within, the individual patients for the recognition of Tax11-19. Sequence analysis of the TCR showed evidence for an oligoclonal expansion of few founder T cells in each patient. Apparent structural motifs were identified for the CDR3 regions of the TCR beta chains. One T-cell clone could be detected within the same patient over a period of 3 years. We suggest that these in vivo clonally expanded T cells might play a role in the pathogenesis of HAM/TSP and provide information on HTLV-1-specific TCR which may elucidate the nature of the T cells that infiltrate the central nervous system in HAM/TSP patients. PMID:8551623

  1. Feline leukemia virus and feline immunodeficiency virus in Canada: Recommendations for testing and management

    OpenAIRE

    Little, Susan; Bienzle, Dorothee; Carioto, Lisa; Chisholm, Hugh; O’Brien, Elizabeth; Scherk, Margie

    2011-01-01

    Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are common and important infectious disease agents of cats in Canada. Seroprevalence data for FeLV and FIV in various populations of Canadian cats are reviewed and recommendations for testing and management of infections by these viruses in cats in Canada are presented. Retrovirus testing in Canada is infrequent in comparison with the United States, and efforts should be focused on reducing physical and other barriers to tes...

  2. Human T-Cell Leukemia Virus Type I-Mediated Repression of PDZ-LIM Domain-Containing Protein 2 Involves DNA Methylation But Independent of the Viral Oncoprotein Tax

    Directory of Open Access Journals (Sweden)

    Pengrong Yan

    2009-10-01

    Full Text Available Human T-cell leukemia virus type I (HTLV-I is the etiological agent of adult T-cell leukemia (ATL. Our recent studies have shown that one important mechanism of HTLV-I-Mediated tumorigenesis is through PDZ-LIM domain-containing protein 2 (PDLIM2 repression, although the involved mechanism remains unknown. Here, we further report that HTLV-I-Mediated PDLIM2 repression was a pathophysiological event and the PDLIM2 repression involved DNA methylation. Whereas DNA methyltransferases 1 and 3b but not 3a were upregulated in HTLV-I-transformed T cells, the hypomethylating agent 5-aza-2′-deoxycytidine (5-aza-dC restored PDLIM2 expression and induced death of these malignant cells. Notably, the PDLIM2 repression was independent of the viral regulatory protein Tax because neither short-term induction nor long-term stable expression of Tax could downregulate PDLIM2 expression. These studies provide important insights into PDLIM2 regulation, HTLV-I leukemogenicity, long latency, and cancer health disparities. Given the efficient antitumor activity with no obvious toxicity of 5-aza-dC, these studies also suggest potential therapeutic strategies for ATL.

  3. Role of immunity in age-related resistance to paralysis after murine leukemia virus infection.

    OpenAIRE

    Hoffman, P M; Robbins, D S; Morse, H C

    1984-01-01

    Resistance to the paralytic effects of a wild mouse (Cas-Br-M) murine leukemia virus infection develops with age and is complete by 10 days of age in susceptible NFS mice. The possibility that cell-mediated immunity plays a significant role in this resistance was suggested by the observation that treatment of 10-day-old mice with antithymocyte serum rendered them susceptible to paralysis. By comparison, mice rendered incapable of generating a humoral immune response by treatment from birth to...

  4. Chromatin disruption in the promoter of Bovine Leukemia Virus during transcriptional activation

    OpenAIRE

    Colin, Laurence; Dekoninck, Ann; Reichert, Michal; Calao, Miriam; Merimi, Makram; Van den Broeke, Anne; Vierendeel, Valérie; Cleuter, Yvette; Burny, Arsène; Rohr, Olivier; Van Lint, Carine

    2011-01-01

    Bovine leukemia virus expression relies on its chromatin organization after integration into the host cell genome. Proviral latency, which results from transcriptional repression in vivo, represents a viral strategy to escape the host immune system and likely allows for tumor progression. Here, we discriminated two types of latency: an easily reactivable latent state of the YR2 provirus and a ‘locked’ latent state of the L267 provirus. The defective YR2 provirus was characterized by the prese...

  5. Functional dissection of the Moloney murine leukemia virus envelope protein gp70.

    OpenAIRE

    Bae, Y.; Kingsman, S M; Kingsman, A J

    1997-01-01

    The envelope protein of Moloney murine leukemia virus (Mo-MLV) is a complex glycoprotein that mediates receptor binding and entry via fusion with cell membranes. By using a series of substitution mutations and truncations in the Mo-MLV external envelope surface protein gp70, we have identified regions important for these processes. Firstly, truncations of gp70 revealed that the minimal continuous receptor-binding region is amino acids 9 to 230, in broad agreement with other studies. Secondly,...

  6. Clinical aspects of feline immunodeficiency and feline leukemia virus infection.

    Science.gov (United States)

    Hartmann, Katrin

    2011-10-15

    Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with a global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FIV can cause an acquired immunodeficiency syndrome that increases the risk of developing opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia) and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less important as a deadly infectious agent as in the last 20 years prevalence has been decreasing in most countries. PMID:21807418

  7. Susceptibility of human lymphoid tissue cultured ex vivo to xenotropic murine leukemia virus-related virus (XMRV infection.

    Directory of Open Access Journals (Sweden)

    Marta Curriu

    Full Text Available BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV was generated after a recombination event between two endogenous murine leukemia viruses during the production of a prostate cancer cell line. Although the associations of the XMRV infection with human diseases appear unlikely, the XMRV is a retrovirus of undefined pathogenic potential, able to replicate in human cells in vitro. Since recent studies using animal models for infection have yielded conflicting results, we set out an ex vivo model for XMRV infection of human tonsillar tissue to determine whether XMRV produced by 22Rv1 cells is able to replicate in human lymphoid organs. Tonsil blocks were infected and infection kinetics and its pathogenic effects were monitored RESULTS: XMRV, though restricted by APOBEC, enters and integrates into the tissue cells. The infection did not result in changes of T or B-cells, immune activation, nor inflammatory chemokines. Infectious viruses could be recovered from supernatants of infected tonsils by reinfecting DERSE XMRV indicator cell line, although these supernatants could not establish a new infection in fresh tonsil culture, indicating that in our model, the viral replication is controlled by innate antiviral restriction factors. CONCLUSIONS: Overall, the replication-competent retrovirus XMRV, present in a high number of laboratories, is able to infect human lymphoid tissue and produce infectious viruses, even though they were unable to establish a new infection in fresh tonsillar tissue. Hereby, laboratories working with cell lines producing XMRV should have knowledge and understanding of the potential biological biohazardous risks of this virus.

  8. NMR study of xenotropic murine leukemia virus-related virus protease in a complex with amprenavir

    International Nuclear Information System (INIS)

    Highlights: ► Protease (PR) of XMR virus (XMRV) was successfully synthesized with cell-free system. ► Interface of XMRV PR with an inhibitor, amprenavir (APV), was identified with NMR. ► Structural heterogeneity is induced for two PR protomers in the APV:PR = 1:2 complex. ► Structural heterogeneity is transmitted even to distant regions from the interface. ► Long-range transmission of structural change may be utilized for drug discovery. -- Abstract: Xenotropic murine leukemia virus-related virus (XMRV) is a virus created through recombination of two murine leukemia proviruses under artificial conditions during the passage of human prostate cancer cells in athymic nude mice. The homodimeric protease (PR) of XMRV plays a critical role in the production of functional viral proteins and is a prerequisite for viral replication. We synthesized XMRV PR using the wheat germ cell-free expression system and carried out structural analysis of XMRV PR in a complex with an inhibitor, amprenavir (APV), by means of NMR. Five different combinatorially 15N-labeled samples were prepared and backbone resonance assignments were made by applying Otting’s method, with which the amino acid types of the [1H, 15N] HSQC resonances were automatically identified using the five samples (Wu et al., 2006) . A titration experiment involving APV revealed that one APV molecule binds to one XMRV PR dimer. For many residues, two distinct resonances were observed, which is thought to be due to the structural heterogeneity between the two protomers in the APV:XMRV PR = 1:2 complex. PR residues at the interface with APV have been identified on the basis of chemical shift perturbation and identification of the intermolecular NOEs by means of filtered NOE experiments. Interestingly, chemical shift heterogeneity between the two protomers of XMRV PR has been observed not only at the interface with APV but also in regions apart from the interface. This indicates that the structural heterogeneity

  9. HIGH EFFICIENCY RETROVIRUS-MEDIATED GENE TRANSFER TO LEUKEMIA CELLS

    Institute of Scientific and Technical Information of China (English)

    FU Jian-xin; CHEN Zi-xing; CEN Jian-nong; WANG Wei; RUAN Chang-geng

    1999-01-01

    Objective: To establish an efficient and safe gene transfer system mediated by retrovirus for gene marking and gene therapy of human leukemia. Method: The retroviral vector LXSN, containing the neomycin resistance (NeoR) gene, was transferred into amphotropic packaging cells GP+envAm12 by liposome transfection or by ecotropic retrovirus transduction. Amphotropic retrovirus in supernatants with higher titer was used to infect human leukemic cell lines NB4, U937, and THP-1.The efficiency of gene transfer was assayed on colonies formed by transduced K562 cells. Results: The titer of DOSPER directly transfected GP+envAm12 cells determined on NIH3T3 cells was 8.0×105 CFU/ml, while that of producer infected with retrovirus was 1.6×107CFU/ml. Integration of NeoR gene into all leukemia cells was confirmed by polymerase chain reaction (PCR).Absence of replication-competent virus was proved by both nested PCR for env gene and marker gene rescue assay. Gene transfer with the efficiency as high as 93.3 to 100% in K562 cells was verified by seminested PCR for integrated NeoR gene on colonies after 7 days' culture.Conclusion: The efficiency and safety of retrovirus mediated gene transfer system might provide an optimal system in gene therapy for leukemia or genetic diseases.

  10. No evidence of murine leukemia virus-related viruses in live attenuated human vaccines.

    Directory of Open Access Journals (Sweden)

    William M Switzer

    Full Text Available BACKGROUND: The association of xenotropic murine leukemia virus (MLV-related virus (XMRV in prostate cancer and chronic fatigue syndrome reported in previous studies remains controversial as these results have been questioned by recent data. Nonetheless, concerns have been raised regarding contamination of human vaccines as a possible source of introduction of XMRV and MLV into human populations. To address this possibility, we tested eight live attenuated human vaccines using generic PCR for XMRV and MLV sequences. Viral metagenomics using deep sequencing was also done to identify the possibility of other adventitious agents. RESULTS: All eight live attenuated vaccines, including Japanese encephalitis virus (JEV (SA-14-14-2, varicella (Varivax, measles, mumps, and rubella (MMR-II, measles (Attenuvax, rubella (Meruvax-II, rotavirus (Rotateq and Rotarix, and yellow fever virus were negative for XMRV and highly related MLV sequences. However, residual hamster DNA, but not RNA, containing novel endogenous gammaretrovirus sequences was detected in the JEV vaccine using PCR. Metagenomics analysis did not detect any adventitious viral sequences of public health concern. Intracisternal A particle sequences closest to those present in Syrian hamsters and not mice were also detected in the JEV SA-14-14-2 vaccine. Combined, these results are consistent with the production of the JEV vaccine in Syrian hamster cells. CONCLUSIONS: We found no evidence of XMRV and MLV in eight live attenuated human vaccines further supporting the safety of these vaccines. Our findings suggest that vaccines are an unlikely source of XMRV and MLV exposure in humans and are consistent with the mounting evidence on the absence of these viruses in humans.

  11. Induction of mouse leukemia by combined ionizing radiation and virus inoculation

    International Nuclear Information System (INIS)

    This paper reported on leukemogenetic effect of γ-rays and T-638 virus in adult Kumming mice. During the period of one year, the incidence of leukemia in the mice of all experimental groups was remarkably higher than that of the control. The induction rate of leukemia was increased in the group which received combined treatment of fractionated total-body irradiation and virus injection, compared with the group which received virus alone. The latent period of induced leukemia in the group of combined treatment was shorter than the corresponding groups with 680 R irradiation and with virus inoculation alone. The results showed that both ionizing radiation and T-638 virus may induce leukemia in mice. Enhancing effect of virus on irradiation was proved by shortening of the latent period of leukemia

  12. Increase of cells expressing PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via PD-L1 blockade

    Directory of Open Access Journals (Sweden)

    Ikebuchi Ryoyo

    2011-09-01

    Full Text Available Abstract The inhibitory receptor programmed death-1 (PD-1 and its ligand, programmed death-ligand 1 (PD-L1 are involved in immune evasion mechanisms for several pathogens causing chronic infections. Blockade of the PD-1/PD-L1 pathway restores anti-virus immune responses, with concomitant reduction in viral load. In a previous report, we showed that, in bovine leukemia virus (BLV infection, the expression of bovine PD-1 is closely associated with disease progression. However, the functions of bovine PD-L1 are still unknown. To investigate the role of PD-L1 in BLV infection, we identified the bovine PD-L1 gene, and examined PD-L1 expression in BLV-infected cattle in comparison with uninfected cattle. The deduced amino acid sequence of bovine PD-L1 shows high homology to the human and mouse PD-L1. The proportion of PD-L1 positive cells, especially among B cells, was upregulated in cattle with the late stage of the disease compared to cattle at the aleukemic infection stage or uninfected cattle. The proportion of PD-L1 positive cells correlated positively with prediction markers for the progression of the disease such as leukocyte number, virus load and virus titer whilst on the contrary, it inversely correlated with the degree of interferon-gamma expression. Blockade of the PD-1/PD-L1 pathway in vitro by PD-L1-specific antibody upregulated the production of interleukin-2 and interferon-gamma, and correspondingly, downregulated the BLV provirus load and the proportion of BLV-gp51 expressing cells. These data suggest that PD-L1 induces immunoinhibition in disease progressed cattle during chronic BLV infection. Therefore, PD-L1 would be a potential target for developing immunotherapies against BLV infection.

  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. Single Amino Acid Insertion in Loop 4 Confers Amphotropic Murine Leukemia Virus Receptor Function upon Murine Pit1

    DEFF Research Database (Denmark)

    Lundorf, Mikkel D.; Pedersen, Finn Skou; O'Hara, Bryan; Pedersen, Lene

    1998-01-01

    Pit1 is the human receptor for gibbon ape leukemia virus (GALV) and feline leukemia virus subgroup B (FeLV-B), while the related human protein Pit2 is a receptor for amphotropic murine leukemia virus (A-MuLV). The A-MuLV-related isolate 10A1 can utilize both Pit1 and Pit2 as receptors. A stretch of...

  15. Significant differences in integration sites of Moloney murine leukemia virus/Moloney murine sarcoma virus retroviral vector carrying recombinant coagulation factor IX in two human cell lines.

    Science.gov (United States)

    Castilho-Fernandes, Andrielle; Fontes, Aparecida Maria; Abraham, Kuruvilla Joseph; de Freitas, Marcela Cristina Corrêa; da Rosa, Nathalia Gonsales; Picanço-Castro, Virginia; de Sousa Russo-Carbolante, Elisa Maria; Covas, Dimas Tadeu

    2015-05-01

    Ligation-mediated-PCR was performed followed by the mapping of 177 and 150 integration sites from HepG2 and Hek293 transduced with chimera vector carrying recombinant human Factor IX (rhFIX) cDNA, respectively. The sequences were analyzed for chromosome preference, CpG, transcription start site (TSS), repetitive elements, fragile sites and target genes. In HepG2, rhFIX was had an increased preference for chromosomes 6 and 17; the median distance to the nearest CpG islands was 15,240 base pairs and 37 % of the integrations occurred in RefSeq genes. In Hek293, rhFIX had an increased preference for chromosome 5; the median distance to the nearest CpG islands was 209,100 base pairs and 74 % of the integrations occurred in RefSeq genes. The integrations in both cell lines were distant from the TSS. The integration patterns associated with this vector are different in each cell line. PMID:25650340

  16. Occurrence of Feline Immunodeficiency Virus and Feline Leukemia Virus Infection in Cats

    OpenAIRE

    Fabiana Alves; Daniela D.S. Rajao; Helen L.D. Puerto; Braz, Gissandra F; Romulo C. Leite; Carlos Mazur; Martins, Almir S; Jenner K.P.D. Reis

    2011-01-01

    Problem statement: The objective of the present work was to evaluate the occurrence of the Feline Immunodeficiency Virus (FIV) and the Feline Leukemia Virus (FeLV) infection in asymptomatic domestic cats in the metropolitan region of Belo Horizonte, Minas Gerais, using the Polymerase Chain Reaction (PCR) for FIV detection and SNAP Combo Plus for FeLV and FIV detection. Approach: Blood samples were collected from the jugular vein of 78 healthy cats, mixed breeds and ages and both sexes. Specif...

  17. Hypercalcemia associated with adult T-cell leukemia/lymphoma (ATL).

    Science.gov (United States)

    Peter, S. A.; Cervantes, J. F.

    1995-01-01

    Hypercalcemia is a frequent manifestation of human T-cell lymphotrophic virus type I (HTLV-I)-associated adult T-cell leukemia/lymphoma (ATL). Human T-cell lymphotrophic virus type I infection is endemic in the Caribbean, Japan, Melanesia, and Africa. This article presents two cases of ATL to increase awareness of the disease by primary care physicians. The management of hypercalcemia is discussed. PMID:7473848

  18. Antibody responses against xenotropic murine leukemia virus-related virus envelope in a murine model.

    Directory of Open Access Journals (Sweden)

    Natalia Makarova

    Full Text Available BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV was recently discovered to be the first human gammaretrovirus that is associated with chronic fatigue syndrome and prostate cancer (PC. Although a mechanism for XMRV carcinogenesis is yet to be established, this virus belongs to the family of gammaretroviruses well known for their ability to induce cancer in the infected hosts. Since its original identification XMRV has been detected in several independent investigations; however, at this time significant controversy remains regarding reports of XMRV detection/prevalence in other cohorts and cell type/tissue distribution. The potential risk of human infection, coupled with the lack of knowledge about the basic biology of XMRV, warrants further research, including investigation of adaptive immune responses. To study immunogenicity in vivo, we vaccinated mice with a combination of recombinant vectors expressing codon-optimized sequences of XMRV gag and env genes and virus-like particles (VLP that had the size and morphology of live infectious XMRV. RESULTS: Immunization elicited Env-specific binding and neutralizing antibodies (NAb against XMRV in mice. The peak titers for ELISA-binding antibodies and NAb were 1:1024 and 1:464, respectively; however, high ELISA-binding and NAb titers were not sustained and persisted for less than three weeks after immunizations. CONCLUSIONS: Vaccine-induced XMRV Env antibody titers were transiently high, but their duration was short. The relatively rapid diminution in antibody levels may in part explain the differing prevalences reported for XMRV in various prostate cancer and chronic fatigue syndrome cohorts. The low level of immunogenicity observed in the present study may be characteristic of a natural XMRV infection in humans.

  19. Mutations of the Kissing-Loop Dimerization Sequence Influence the Site Specificity of Murine Leukemia Virus Recombination In Vivo

    OpenAIRE

    Mikkelsen, Jacob Giehm; Lund, Anders H.; Duch, Mogens; Pedersen, Finn Skou

    2000-01-01

    The genetic information of retroviruses is retained within a dimeric RNA genome held together by intermolecular RNA-RNA interactions near the 5′ ends. Coencapsidation of retrovirus-derived RNA molecules allows frequent template switching of the virus-encoded reverse transcriptase during DNA synthesis in newly infected cells. We have previously shown that template shifts within the 5′ leader of murine leukemia viruses occur preferentially within the kissing stem-loop motif, a cis element cruci...

  20. Seroprevalence of Toxoplasma gondii and concurrent Bartonella spp., feline immunodeficiency virus, feline leukemia virus, and Dirofilaria immitis infections in Egyptian cats

    Science.gov (United States)

    Toxoplasma gondii and Bartonella spp. are zoonotic pathogens of cats. Feline Immunodeficiency Virus (FIV), and Feline Leukemia Virus (FeLv) are related to Human Immunodeficiency Virus, and Human Leukemia Virus, respectively, and these viruses are immunosuppressive. In the present study, the prevalen...

  1. Immunotoxin Therapy for Relapsed Hairy Cell Leukemia

    Science.gov (United States)

    In this trial, patients with hairy cell leukemia who have relapsed multiple times or not responded to prior chemotherapy will be treated with an experimental immunotoxin called moxetumomab pasudotox given intravenously on days 1, 3, and 5 of 28-day cycles

  2. Induction of T-cell immunity against leukemia by dendritic cells pulsed with total RNA isolated from leukemia cells

    Institute of Scientific and Technical Information of China (English)

    李牧; 尤胜国; 葛薇; 马双; 马楠; 赵春华

    2003-01-01

    Objectives To assess the feasibility and efficacy of eliciting leukemia-specific T-cell responses in syngeneic mice in vitro and in vivo using dendritic cells (DCs) pulsed with total RNA from leukemia cells.Methods DCs generated from bone marrow culture in vitro in the presence of combined cytokines were pulsed with cellular total RNA isolated from cultured L615 cells by cationic lipid 1,2-dioleoyloxy-3-(trimethylammonium) propane (DOTAP). T-cell responses were evaluated by in vitro proliferation, and cytotoxicity assay. And in vivo immune protection and proghosis of mice with leukemia were studied.Conclusions These data support the use of DCs/RNA vaccine as a feasible and effective route to elicit leukemia immunity against unidentified leukemia-associated antigens for treatment of leukemia-bearing animals.

  3. In vitro generation of cytotoxic lymphocytes against radiation-and radiation leukemia virus-induced tumors. III. Suppression of anti-tumor immunity in vitro by lymphocytes of mice undergoing radiation leukemia virus-induced leukemogenesis

    International Nuclear Information System (INIS)

    Adult C57BL/6 mice exposed to fractionated irradiation or inoculated with the radiation leukemia virus (RadLV), develop high incidence (80 to 100%) of lymphatic leukemias within 3 to 6 months. RadLV-induced lymphomas can elicit cytotoxic responses in vitro in lymphocytes of preimmunized syngeneic mice. As soon as 5 d after RadLV inoculation, and during the entire leukemogenic process, suppressor T cells are detectable in the spleen that are capable of specifically abrogating generation of syngeneic anti-tumor cytotoxic cells in vitro. Mice exposed to fractionated x irradiation do not develop suppressor cells. These findings suggest that although RadLV has been isolated from radiation-induced leukemias, x-ray- and RadLV-induced leukemogenesis do not seem to involve a common viral etilogy, and that induction of suppressor cells during RadLV leukemogenesis may be essential for tumor progression

  4. Increase of cells expressing PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via PD-L1 blockade

    OpenAIRE

    Ikebuchi Ryoyo; Konnai Satoru; Shirai Tatsuya; Sunden Yuji; Murata Shiro; Onuma Misao; Ohashi Kazuhiko

    2011-01-01

    Abstract The inhibitory receptor programmed death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1) are involved in immune evasion mechanisms for several pathogens causing chronic infections. Blockade of the PD-1/PD-L1 pathway restores anti-virus immune responses, with concomitant reduction in viral load. In a previous report, we showed that, in bovine leukemia virus (BLV) infection, the expression of bovine PD-1 is closely associated with disease progression. However, the functions ...

  5. Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth

    International Nuclear Information System (INIS)

    Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation, and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.

  6. Sodium-Dependent myo-Inositol Transporter 1 Is a Cellular Receptor for Mus cervicolor M813 Murine Leukemia Virus

    OpenAIRE

    Hein, Sibyll; Prassolov, Vladimir; Zhang, Yuanming; Ivanov, Dmitry; Löhler, Jürgen; Susan R Ross; Stocking, Carol

    2003-01-01

    Retrovirus infection is initiated by binding of the surface (SU) portion of the viral envelope glycoprotein (Env) to specific receptors on cells. This binding triggers conformational changes in the transmembrane portion of Env, leading to membrane fusion and cell entry, and is thus a major determinant of retrovirus tissue and species tropism. The M813 murine leukemia virus (MuLV) is a highly fusogenic gammaretrovirus, isolated from Mus cervicolor, whose host range is limited to mouse cells. T...

  7. Immunotherapy of murine leukemia. Efficacy of passive serum therapy of Friend leukemia virus-induced disease in immunocompromised mice

    International Nuclear Information System (INIS)

    Previous studies have demonstrated that the passive therapy of Friend murine leukemia virus (F-MuLV)-induced disease with chimpanzee anti-F-MuLV serum is accompanied by the development of host antiviral humoral and cellular immunity, the latter measurable in adoptive transfer protocols and by the ability of serum-protected mice to resist virus rechallenge. The present study was designed to further examine the contribution of various compartments of the host immune system to serum therapy itself, as well as to the acquired antiviral immunity that develops in serum-protected mice, through the use of naturally immunocompromised animals [e.g., nude athymic mice and natural killer (NK)-deficient beige mutant mice] or mice treated with immunoabrogating agents such as sublethal irradiation, cyclophosphamide [Cytoxan (Cy)], cortisone, and 89Sr. The studies in nude mice indicate that while mature T-cells are not needed for effective serum therapy, they do appear to be necessary for the long-term resistance of serum-protected mice to virus rechallenge and for the generation of the cell population(s) responsible for adoptive transfer of antiviral immunity. Furthermore, this acquired resistance is not due to virus neutralization by serum antibodies since antibody-negative, Cy-treated, serum-protected mice still reject the secondary virus infection. Lastly, while the immunocompromise systems examined did effect various host antiviral immune responses, none of them, including the NK-deficient beige mutation, significantly diminished the efficacy of the passive serum therapy of F-MuLV-induced disease

  8. Heat Shock Enhances the Expression of the Human T Cell Leukemia Virus Type-I (HTLV-I) Trans-Activator (Tax) Antigen in Human HTLV-I Infected Primary and Cultured T Cells.

    Science.gov (United States)

    Kunihiro, Marie; Fujii, Hideki; Miyagi, Takuya; Takahashi, Yoshiaki; Tanaka, Reiko; Fukushima, Takuya; Ansari, Aftab A; Tanaka, Yuetsu

    2016-01-01

    The environmental factors that lead to the reactivation of human T cell leukemia virus type-1 (HTLV-I) in latently infected T cells in vivo remain unknown. It has been previously shown that heat shock (HS) is a potent inducer of HTLV-I viral protein expression in long-term cultured cell lines. However, the precise HTLV-I protein(s) and mechanisms by which HS induces its effect remain ill-defined. We initiated these studies by first monitoring the levels of the trans-activator (Tax) protein induced by exposure of the HTLV-I infected cell line to HS. HS treatment at 43 °C for 30 min for 24 h led to marked increases in the level of Tax antigen expression in all HTLV-I-infected T cell lines tested including a number of HTLV-I-naturally infected T cell lines. HS also increased the expression of functional HTLV-I envelope gp46 antigen, as shown by increased syncytium formation activity. Interestingly, the enhancing effect of HS was partially inhibited by the addition of the heat shock protein 70 (HSP70)-inhibitor pifithlin-μ (PFT). In contrast, the HSP 70-inducer zerumbone (ZER) enhanced Tax expression in the absence of HS. These data suggest that HSP 70 is at least partially involved in HS-mediated stimulation of Tax expression. As expected, HS resulted in enhanced expression of the Tax-inducible host antigens, such as CD83 and OX40. Finally, we confirmed that HS enhanced the levels of Tax and gp46 antigen expression in primary human CD4⁺ T cells isolated from HTLV-I-infected humanized NOD/SCID/γc null (NOG) mice and HTLV-I carriers. In summary, the data presented herein indicate that HS is one of the environmental factors involved in the reactivation of HTLV-I in vivo via enhanced Tax expression, which may favor HTLV-I expansion in vivo. PMID:27409630

  9. 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

  10. Symmetrical base preferences surrounding HIV-1, avian sarcoma/leukosis virus, and murine leukemia virus integration sites

    OpenAIRE

    Holman, Alexander G; Coffin, John M.

    2005-01-01

    To investigate retroviral integration targeting on a nucleotide scale, we examined the base frequencies directly surrounding cloned in vivo HIV-1, murine leukemia virus, and avian sarcoma/leukosis virus integrations. Base preferences of up to 2-fold the expected frequencies were found for three viruses, representing P values down to

  11. Hematopoietic stem cells and progenitors of chronic myeloid leukemia express leukemia-associated antigens: implications for the graft-versus-leukemia effect and peptide vaccine-based immunotherapy

    OpenAIRE

    Yong, Agnes S.M.; Keyvanfar, Keyvan; Eniafe, Rhoda; Savani, Bipin N.; Rezvani, Katayoun; Sloand, Elaine M.; Goldman, John M.; Barrett, A. John

    2008-01-01

    The cure of chronic myeloid leukemia (CML) patients following allogeneic stem cell transplantation (SCT) is attributed to graft-versus-leukemia (GVL) effects targeting alloantigens and/or leukemia-associated antigens (LAA) on leukemia cells. To assess the potential of LAA-peptide vaccines in eliminating leukemia in CML patients, we measured WT1, PR3, ELA2 and PRAME expression in CD34+ progenitor subpopulations in CML patients and compared them with minor histocompatibility antigens (mHAgs) HA...

  12. Cell death sensitization of leukemia cells by opioid receptor activation

    Science.gov (United States)

    Friesen, Claudia; Roscher, Mareike; Hormann, Inis; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf A.; Debatin, Klaus-Michael; Miltner, Erich

    2013-01-01

    Cyclic AMP (cAMP) regulates a number of cellular processes and modulates cell death induction. cAMP levels are altered upon stimulation of specific G-protein-coupled receptors inhibiting or activating adenylyl cyclases. Opioid receptor stimulation can activate inhibitory Gi-proteins which in turn block adenylyl cyclase activity reducing cAMP. Opioids such as D,L-methadone induce cell death in leukemia cells. However, the mechanism how opioids trigger apoptosis and activate caspases in leukemia cells is not understood. In this study, we demonstrate that downregulation of cAMP induced by opioid receptor activation using the opioid D,L-methadone kills and sensitizes leukemia cells for doxorubicin treatment. Enhancing cAMP levels by blocking opioid-receptor signaling strongly reduced D,L-methadone-induced apoptosis, caspase activation and doxorubicin-sensitivity. Induction of cell death in leukemia cells by activation of opioid receptors using the opioid D,L-methadone depends on critical levels of opioid receptor expression on the cell surface. Doxorubicin increased opioid receptor expression in leukemia cells. In addition, the opioid D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux in leukemia cells, suggesting that the opioid D,L-methadone as well as doxorubicin mutually increase their cytotoxic potential. Furthermore, we found that opioid receptor activation using D,L-methadone alone or in addition to doxorubicin inhibits tumor growth significantly in vivo. These results demonstrate that opioid receptor activation via triggering the downregulation of cAMP induces apoptosis, activates caspases and sensitizes leukemia cells for doxorubicin treatment. Hence, opioid receptor activation seems to be a promising strategy to improve anticancer therapies. PMID:23633472

  13. A review of feline leukemia virus and feline immunodeficiency virus seroprevalence in cats in Canada.

    Science.gov (United States)

    Little, Susan

    2011-10-15

    Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are common and important infectious diseases of cats in Canada. Prevalence data are necessary to define prophylactic, management, and therapeutic measures for stray, feral and owned cats. Recently, comprehensive data on the seroprevalence of retrovirus infections of cats in Canada have become available and are reviewed. Further investigation into geographic variations in retrovirus seroprevalence within Canada is warranted, and may provide information to improve recommendations for testing and prevention. As well, more information is needed on FIV subtypes in Canada to improve diagnostics and vaccines, as well as to provide information on disease outcomes. PMID:21757241

  14. Seroprevalence of feline leukemia virus and feline immunodeficiency virus infection among cats in Canada

    OpenAIRE

    Little, Susan; Sears, William; Lachtara, Jessica; Bienzle, Dorothee

    2009-01-01

    The purposes of this study were to determine the seroprevalence of feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) infection among cats in Canada and to identify risk factors for seropositivity. Signalment, lifestyle factors, and test results for FeLV antigen and FIV antibody were analyzed for 11 144 cats from the 10 Canadian provinces. Seroprevalence for FIV antibody was 4.3% and seroprevalence for FeLV antigen was 3.4%. Fifty-eight cats (0.5%) were seropositive for both...

  15. Expression of IMP1 enhances production of murine leukemia virus vector by facilitating viral genomic RNA packaging.

    Directory of Open Access Journals (Sweden)

    Yun Mai

    Full Text Available Murine leukemia virus (MLV-based retroviral vector is widely used for gene transfer. Efficient packaging of the genomic RNA is critical for production of high-titer virus. Here, we report that expression of the insulin-like growth factor II mRNA binding protein 1 (IMP1 enhanced the production of infectious MLV vector. Overexpression of IMP1 increased the stability of viral genomic RNA in virus producer cells and packaging of the RNA into progeny virus in a dose-dependent manner. Downregulation of IMP1 in virus producer cells resulted in reduced production of the retroviral vector. These results indicate that IMP1 plays a role in regulating the packaging of MLV genomic RNA and can be used for improving production of retroviral vectors.

  16. Ku protein as a potential human T-cell leukemia virus type 1 (HTLV-1 Tax target in clastogenic chromosomal instability of mammalian cells

    Directory of Open Access Journals (Sweden)

    Iwanaga Yoichi

    2005-07-01

    Full Text Available Abstract The HTLV-1 Tax oncoprotein rapidly induces cytogenetic damage which can be measured by a significant increase in the number of micronuclei (MN in cells. Tax is thought to have both aneuploidogenic and clastogenic effects. To examine the cellular target for Tax which might mechanistically explain the clastogenic phenomenon, we tested the ability of Tax to induce MN in rodents cells genetically defective for either the Ku80 protein or the catalytic subunit of DNA protein kinase (DNAPKcs. We found that cells genetically mutated in Ku80 were refractory to Tax's induction of MN while cells knocked-out for DNAPKcs showed increased number of Tax-induced MN. Using a cytogenetic method termed FISHI (Fluorescent In Situ Hybridization and Incorporation which measures the number of DNA-breaks in cells that contained unprotected 3'-OH ends, we observed that Tax increased the prevalence of unprotected DNA breaks in Ku80-intact cells, but not in Ku80-mutated cells. Taken together, our findings suggest Ku80 as a cellular factor targeted by Tax in engendering clastogenic DNA damage.

  17. Ku protein as a potential human T-cell leukemia virus type 1 (HTLV-1) Tax target in clastogenic chromosomal instability of mammalian cells.

    Science.gov (United States)

    Majone, Franca; Luisetto, Roberto; Zamboni, Daniela; Iwanaga, Yoichi; Jeang, Kuan-Teh

    2005-01-01

    The HTLV-1 Tax oncoprotein rapidly induces cytogenetic damage which can be measured by a significant increase in the number of micronuclei (MN) in cells. Tax is thought to have both aneuploidogenic and clastogenic effects. To examine the cellular target for Tax which might mechanistically explain the clastogenic phenomenon, we tested the ability of Tax to induce MN in rodents cells genetically defective for either the Ku80 protein or the catalytic subunit of DNA protein kinase (DNAPKcs). We found that cells genetically mutated in Ku80 were refractory to Tax's induction of MN while cells knocked-out for DNAPKcs showed increased number of Tax-induced MN. Using a cytogenetic method termed FISHI (Fluorescent In Situ Hybridization and Incorporation) which measures the number of DNA-breaks in cells that contained unprotected 3'-OH ends, we observed that Tax increased the prevalence of unprotected DNA breaks in Ku80-intact cells, but not in Ku80-mutated cells. Taken together, our findings suggest Ku80 as a cellular factor targeted by Tax in engendering clastogenic DNA damage. PMID:16014171

  18. Quantitative Proteomics Analysis of Leukemia Cells.

    Science.gov (United States)

    Halbach, Sebastian; Dengjel, Jörn; Brummer, Tilman

    2016-01-01

    Chronic myeloid leukemia (CML) is driven by the oncogenic fusion kinase Bcr-Abl, which organizes its own signaling network with various proteins. These proteins, their interactions, and their role in relevant signaling pathways can be analyzed by quantitative mass spectrometry (MS) approaches in various models systems, e.g., in cell culture models. In this chapter, we describe in detail immunoprecipitations and quantitative proteomics analysis using stable isotope labeling by amino acids in cell culture (SILAC) of components of the Bcr-Abl signaling pathway in the human CML cell line K562. PMID:27581145

  19. Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias

    Directory of Open Access Journals (Sweden)

    Jakubowski Ann A

    2009-12-01

    Full Text Available Abstract We have described a severe combined immunodeficiency (SCID mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL and 66 acute myeloid leukemia (AML in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8% displayed an aggressive growth pattern, 14 (10.5% displayed an indolent growth pattern and 74 (55.6% did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course.

  20. CAR-pNK Cell Immunotherapy in CD7 Positive Leukemia and Lymphoma

    Science.gov (United States)

    2016-07-11

    Acute Myeloid Leukemia; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; T-cell Prolymphocytic Leukemia; T-cell Large Granular Lymphocytic Leukemia; Peripheral T-cell Lymphoma, NOS; Angioimmunoblastic T-cell Lymphoma; Extranodal NK/T-cell Lymphoma, Nasal Type; Enteropathy-type Intestinal T-cell Lymphoma; Hepatosplenic T-cell Lymphoma

  1. Impairment of alternative splice sites defining a novel gammaretroviral exon within gag modifies the oncogenic properties of Akv murine leukemia virus

    DEFF Research Database (Denmark)

    Sørensen, Annette Balle; Lund, Anders H; Kunder, Sandra;

    2007-01-01

    BACKGROUND: Mutations of an alternative splice donor site located within the gag region has previously been shown to broaden the pathogenic potential of the T-lymphomagenic gammaretrovirus Moloney murine leukemia virus, while the equivalent mutations in the erythroleukemia inducing Friend murine...... leukemia virus seem to have no influence on the disease-inducing potential of this virus. In the present study we investigate the splice pattern as well as the possible effects of mutating the alternative splice sites on the oncogenic properties of the B-lymphomagenic Akv murine leukemia virus. RESULTS: By...... examination of the tumors showed that the introduced synonymous gag mutations have a significant influence on the phenotype of the induced tumors, changing the distribution of the different types as well as generating tumors of additional specificities such as de novo diffuse large B cell lymphoma (DLBCL) and...

  2. Functional impairment of Tax-specific but not cytomegalovirus-specific CD8+ T lymphocytes in a minor population of asymptomatic human T-cell leukemia virus type 1-carriers

    Directory of Open Access Journals (Sweden)

    Takamori Ayako

    2011-12-01

    Full Text Available Abstract Background Human T-cell leukemia virus type 1 (HTLV-1 causes adult T-cell leukemia (ATL and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP in a small percentage of infected individuals. ATL is often associated with general immune suppression and an impaired HTLV-1-specific T-cell response, an important host defense system. We previously found that a small fraction of asymptomatic HTLV-1-carriers (AC already showed impaired T-cell responses against the major target antigen, Tax. However, it is unclear whether the impaired HTLV-1 Tax-specific T-cell response in these individuals is an HTLV-1-specific phenomenon, or merely reflects general immune suppression. In this study, in order to characterize the impaired HTLV-1-specific T-cell response, we investigated the function of Tax-specific CD8+ T-cells in various clinical status of HTLV-1 infection. Results By using tetramers consisting of HLA-A*0201, -A*2402, or -A*1101, and corresponding Tax epitope peptides, we detected Tax-specific CD8+ T-cells in the peripheral blood from 87.0% of ACs (n = 20/23 and 100% of HAM/TSP patients (n = 18/18 tested. We also detected Tax-specific CD8+ T-cells in 38.1% of chronic type ATL (cATL patients (n = 8/21, although its frequencies in peripheral blood CD8+ T cells were significantly lower than those of ACs or HAM/TSP patients. Tax-specific CD8+ T-cells detected in HAM/TSP patients proliferated well in culture and produced IFN-γ when stimulated with Tax peptides. However, such functions were severely impaired in the Tax-specific CD8+ T-cells detected in cATL patients. In ACs, the responses of Tax-specific CD8+ T-cells were retained in most cases. However, we found one AC sample whose Tax-specific CD8+ T-cells hardly produced IFN-γ, and failed to proliferate and express activation (CD69 and degranulation (CD107a markers in response to Tax peptide. Importantly, the same AC sample contained cytomegalovirus (CMV pp65-specific CD8+ T-cells

  3. Delayed-onset enzootic bovine leukosis possibly caused by superinfection with bovine leukemia virus mutated in the pol gene.

    Science.gov (United States)

    Watanabe, Tadaaki; Inoue, Emi; Mori, Hiroshi; Osawa, Yoshiaki; Okazaki, Katsunori

    2015-08-01

    Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis (EBL), to which animals are most susceptible at 4-8 years of age. In this study, we examined tumor cells associated with EBL in an 18-year-old cow to reveal that the cells carried at least two different copies of the virus, one of which was predicted to encode a reverse transcriptase (RT) lacking ribonuclease H activity and no integrase. Such a deficient enzyme may exhibit a dominant negative effect on the wild-type RT and cause insufficient viral replication, resulting in delayed tumor development in this cow. PMID:26025155

  4. 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

  5. Immunological Analyses of Leukemia Stem Cells.

    Science.gov (United States)

    Naka, Kazuhito; Takihara, Yoshihiro

    2016-01-01

    Traditionally, the intracellular localization and expression levels of specific proteins in CML Leukemia stem cells (LSCs) have been evaluated by fluorescence immunohistochemistry (FIHC). More recently, Duolink(®) in situ PLA technology has opened up a new and more quantitative way to evaluate signal transduction, posttranslational modification, and protein-protein interaction at the single-stem-cell level. This novel methodology, which employs two antibody-based probes, has already increased our understanding of the biology of the rare CML LSC population. In the future, the use of this approach may contribute to the development of novel therapeutics aimed at eradicating CML LSCs in CML patients. PMID:27581137

  6. Localized nasal cavity, sinus, and massive bilateral orbital involvement by human T cell leukemia virus 1 adult T cell lymphoma, with epidermal hypertrophy due to mite infestation

    Directory of Open Access Journals (Sweden)

    Albert S. Braverman

    2010-12-01

    Full Text Available HTLV1 adult T cell lymphoma occurs tends to be widely disseminated and aggressive, with only brief responses to chemotherapy. Aside from cervical adenopathy, involvement of head and neck structures is uncommon and orbital involvement rare. We report a case of nasal cavity HTLV lymphoma with massive bilateral orbital involvement and proptosis, resulting in complete left and partial right eye amaurosis. No other sites of disease were found. Response to chemotherapy was rapid and complete, with almost complete restoration of vision and oculo-motor function; the patient has remained in remission for one year. An associated problem was striking bilateral hypertrophic, hyperkeratotic eyelid and breast lesions due to mite infestation. 

  7. Feline leukemia virus and feline immunodeficiency virus in Canada: recommendations for testing and management.

    Science.gov (United States)

    Little, Susan; Bienzle, Dorothee; Carioto, Lisa; Chisholm, Hugh; O'Brien, Elizabeth; Scherk, Margie

    2011-08-01

    Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are common and important infectious disease agents of cats in Canada. Seroprevalence data for FeLV and FIV in various populations of Canadian cats are reviewed and recommendations for testing and management of infections by these viruses in cats in Canada are presented. Retrovirus testing in Canada is infrequent in comparison with the United States, and efforts should be focused on reducing physical and other barriers to testing, and on education of veterinarians, veterinary team members, and cat owners regarding the importance of testing. New test methodologies for FeLV and FIV are emerging, and should be independently evaluated in order to provide practitioners with information on test reliability. Finally, more information is needed on FIV subtypes in Canada to improve diagnostics and vaccines, and to provide information on disease outcomes. PMID:22294790

  8. Leukemia Mediated Endothelial Cell Activation Modulates Leukemia Cell Susceptibility to Chemotherapy through a Positive Feedback Loop Mechanism.

    Directory of Open Access Journals (Sweden)

    Bahareh Pezeshkian

    Full Text Available In acute myeloid leukemia (AML, the chances of achieving disease-free survival are low. Studies have demonstrated a supportive role of endothelial cells (ECs in normal hematopoiesis. Here we show that similar intercellular relationships exist in leukemia. We demonstrate that leukemia cells themselves initiate these interactions by directly modulating the behavior of resting ECs through the induction of EC activation. In this inflammatory state, activated ECs induce the adhesion of a sub-set of leukemia cells through the cell adhesion molecule E-selectin. These adherent leukemia cells are sequestered in a quiescent state and are unaffected by chemotherapy. The ability of adherent cells to later detach and again become proliferative following exposure to chemotherapy suggests a role of this process in relapse. Interestingly, differing leukemia subtypes modulate this process to varying degrees, which may explain the varied response of AML patients to chemotherapy and relapse rates. Finally, because leukemia cells themselves induce EC activation, we postulate a positive-feedback loop in leukemia that exists to support the growth and relapse of the disease. Together, the data defines a new mechanism describing how ECs and leukemia cells interact during leukemogenesis, which could be used to develop novel treatments for those with AML.

  9. Protection against retroviral diseases after vaccination is conferred by interference to superinfection with attenuated murine leukemia viruses.

    OpenAIRE

    Corbin, A.; Sitbon, M.

    1993-01-01

    Cell cultures expressing a retroviral envelope are relatively resistant to superinfection by retroviruses which bear envelopes using the same receptor. We tested whether this phenomenon, known as interference to superinfection, might confer protection against retroviral diseases. Newborn mice first inoculated with the attenuated strain B3 of Friend murine leukemia virus (F-MuLV) were protected against severe early hemolytic anemia and nonacute anemiant erythroleukemia induced by the virulent ...

  10. Conformation-specific antibodies targeting the trimer-of-hairpins motif of the human T-cell leukemia virus type 1 transmembrane glycoprotein recognize the viral envelope but fail to neutralize viral entry.

    Science.gov (United States)

    Mirsaliotis, Antonis; Nurkiyanova, Kulpash; Lamb, Daniel; Woof, Jenny M; Brighty, David W

    2007-06-01

    Human T-cell leukemia virus type 1 (HTLV-1) entry into cells is dependent upon the viral envelope glycoprotein-catalyzed fusion of the viral and cellular membranes. Following receptor activation of the envelope, the transmembrane glycoprotein (TM) is thought to undergo a series of fusogenic conformational transitions through a rod-like prehairpin intermediate to a compact trimer-of-hairpins structure. Importantly, synthetic peptides that interfere with the conformational changes of TM are potent inhibitors of membrane fusion and HTLV-1 entry, suggesting that TM is a valid target for antiviral therapy. To assess the utility of TM as a vaccine target and to explore further the function of TM in HTLV-1 pathogenesis, we have begun to examine the immunological properties of TM. Here we demonstrate that a recombinant trimer-of-hairpins form of the TM ectodomain is strongly immunogenic. Monoclonal antibodies raised against the TM immunogen specifically bind to trimeric forms of TM, including structures thought to be important for membrane fusion. Importantly, these antibodies recognize the envelope on virally infected cells but, surprisingly, fail to neutralize envelope-mediated membrane fusion or infection by pseudotyped viral particles. Our data imply that, even in the absence of overt membrane fusion, there are multiple forms of TM on virally infected cells and that some of these display fusion-associated structures. Finally, we demonstrate that many of the antibodies possess the ability to recruit complement to TM, suggesting that envelope-derived immunogens capable of eliciting a combination of neutralizing and complement-fixing antibodies would be of value as subunit vaccines for intervention in HTLV infections. PMID:17376912

  11. Methylation of Gene CHFR Promoter in Acute Leukemia Cells

    Institute of Scientific and Technical Information of China (English)

    GONG Hui; LIU Wengli; ZHOU Jianfeng; XU Huizhen

    2005-01-01

    Summary: In order to explore whether gene CHFR was inactivated by methylation in leukemia cells, the expression of CHFR was examined before and after treatment with demethylation agent in Molt-4, Jurkat and U937 leukemia cell lines by means of RT-PCR. The methylation of promoter in Molt-4, Jurkat and U937 cells as well as 41 acute leukemia patients was analyzed by MS-PCR. The results showed that methylation of CHFR promoter was inactivated and could be reversed by treatment with a demethylating agent in Molt-4, Jurkat and U937. CHFR promoter methylation was detected in 39 % of acute leukemia patients. There was no difference in incidence of CHFR promoter methylation between acute myelocytic leukemia and acute lymphocytic leukemia. In conclusion, CHFR is frequently inactivated in acute leukemia and is a good candidate for the leukemia supper gene. By affecting mitotic checkpoint function, CHFR inactivation likely plays a key role in tumorigenesis in acute leukemia. Moreover, the methylation of gene CHFR appears to be a good index with which to predict the sensitivity of acute leukemia to microtubule inhibitors.

  12. Immunity and suppression in radiation- and radiation leukemia virus (RADLV)-induced leukemogenesis

    International Nuclear Information System (INIS)

    Adult C57BL/6 (B6) mice exposed to fractionated irradiation or inoculated with a highly leukemogenic RadLV (A-RadLV) develop high incidence of lymphatic leukemias after a latency of 3-5 months. Inoculation of a low leukemogenic RadLV variant (D-RadLV) does not result in lymphoma development unless the animals receive a single, sublethal dose of irradiation. Whereas virus-induced primary lymphomas produce virus, express gp70 and are all immunogenic, those induced by X-rays are devoid of virus expression and are not immunogenic. A-RadLV inoculation into B6 mice is associated with early induction of virus specific, cyclophosphamide sensitive suppressor T cells which are capable of abrogating a potential antitumor immune responsiveness. D-RadLV, on the other hand, induces reactive T lymphocytes that arrest leukemogenesis unless their function is impaired by irradiation. In (B6 x BALB/c)F1 mice both A-RadLV and D-RadLV leukemogenesis depend on sublethal irradiation of the host, and both induce reactive T cells. These results suggest that (a) RadLV and X-ray induced leukemogeneses involve different etiologies. (b) Different leukemogenic treatments evoke different host responses early in latency which can either sustain or interfere with lymphoma progression. (author)

  13. A rapid bioassay to monitor murine leukemia virus infection in mice using cellular gp71 binding

    International Nuclear Information System (INIS)

    A rapid and sensitive bioassay based on the availability of cell surface receptors for the binding of purified envelope glycoprotein, gp71, of Rauscher murine leukemia virus (R-MuLV) was developed to serially monitor viral-induced leukemogenesis in individual BALB/cAnN mice. The specificity of the bioassay was demonstrated by the competition of [125I]gp71 cellular binding with murine ecotropic viruses, purified unlabelled R-MuLV envelope glycoprotein and by antiserum to R-MuLV gp71. In contrast, there was no effect on the [125I]gp71 binding level with the addition of murine xenotropic viruses, R-MuLV p30, or several other proteins. The [125I]gp71 binding level of circulating leukocytes was significantly (P < 0.05) reduced in mice after R-MuLV infection. The reduction of cellular gp71 binding developed in two stages and the latter stage was highly dependent (P < 0.05) on circulating infections virus titer. Using this technique, the gp71 cellular binding levels of 48-60 individual mice can be assayed in a 4 h period. The advantages of this bioassay compared to standard immunological and tissue culture techniques used in studying retrovirus expression and viral-cell interactions are discussed. (Auth.)

  14. 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 ...

  15. Mutations of the kissing-loop dimerization sequence influence the site specificity of murine leukemia virus recombination in vivo

    DEFF Research Database (Denmark)

    Mikkelsen, J G; Lund, Anders Henrik; Duch, M; Pedersen, F S

    2000-01-01

    -cycle transfer of Akv murine leukemia virus-based vectors harboring defective primer binding site sequences, we now report that modifications of the kissing-loop structure, ranging from a deletion of the entire sequence to introduction of a single point mutation in the loop motif, significantly disturb site...... synthesis in newly infected cells. We have previously shown that template shifts within the 5' leader of murine leukemia viruses occur preferentially within the kissing stem-loop motif, a cis element crucial for in vitro RNA dimer formation. By use of a forced recombination approach based on single...... specificity of recombination within the highly structured 5' leader region. In addition, we find that an intact kissing-loop sequence favors optimal RNA encapsidation and vector transduction. Our data are consistent with the kissing-loop dimerization model and suggest that a direct intermolecular RNA...

  16. Role of the Cytoplasmic Tail of Ecotropic Moloney Murine Leukemia Virus Env Protein in Fusion Pore Formation

    OpenAIRE

    Melikyan, Grigory B.; Markosyan, Ruben M.; Brener, Sofya A.; Rozenberg, Yanina; Cohen, Fredric S.

    2000-01-01

    Fusion between cells expressing envelope protein (Env) of Moloney murine leukemia virus and target cells were studied by use of video fluorescence microscopy and electrical capacitance measurements. When the full-length 632-amino-acid residue Env was expressed, fusion did not occur at all for 3T3 cells as target and only somewhat for XC6 cells. Expression of Env 616*—a construct of Env with the last 16 amino acid residues (617 to 632; the R peptide) deleted from its C terminus to match the pr...

  17. Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients

    Institute of Scientific and Technical Information of China (English)

    Jian-Hua Yu; Jing-Tao Dong; Yong-Qian Jia; Neng-Gang Jiang; Ting-Ting Zeng; Hong Xu; Xian-Ming Mo

    2013-01-01

    Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease.We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development,including IL-7Rα (CD127),cytoplasmic CD79a (cCD79a),CD19,VpreB (CD179a),and slgM,which are successive and essential for progression of B cells along their developmental pathway.Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous,with the leukemic cell population differing from case to case.Through the comprehensive analysis of immunophenotypic patterns,the profiles of patient-specific composite leukemia cell populations could provide detailed information helpful for the diagnosis,therapeutic monitoring,and individualized therapies for common ALL.

  18. Surface proteins of radiation-induced and radiation leukemia virus-induced thymic lymphosarcomas in mice

    International Nuclear Information System (INIS)

    Thymic lymphosarcomas (TLS) were induced in C57BL mice by X-rays or by Radiation Leukemia Virus (RadLV) and their surface glycoproteins (gps) compared after cell-surface radio-iodination and polyacrylamide gel electrophoresis (SDS-PAGE). All lymphocytic antigens tested (T200, 170/100, Thy-1) and proteins with apparent molecular weight (Mr) around 120,000 and 100,000 were present on all tumours, as well as retrovirus - encoded proteins but considerable variation in the Mr of several serologically-related proteins was observed. Therefore, the TLS in C57BL mice form a heterogeneous group, suggesting that T cells can be transformed at different stages of maturation. The possibility that transformation allows or even triggers differentiation is also entertained. (author)

  19. Molecular cloning of osteoma-inducing replication-competent murine leukemia viruses from the RFB osteoma virus stock

    DEFF Research Database (Denmark)

    Pedersen, Lene; Behnisch, Werner; Schmidt, Jörg;

    1992-01-01

    We report the molecular cloning of two replication-competent osteoma-inducing murine leukemia viruses from the RFB osteoma virus stock (M. P. Finkel, C. A. Reilly, Jr., B. O. Biskis, and I. L. Greco, p. 353-366, in C. H. G. Price and F. G. M. Ross, ed., Bone--Certain Aspects of Neoplasia, 1973......). Like the original RFB osteoma virus stock, viruses derived from the molecular RFB clones induced multiple osteomas in mice of the CBA/Ca strain. The cloned RFB viruses were indistinguishable by restriction enzyme analysis and by nucleotide sequence analysis of their long-terminal-repeat regions and...

  20. Role of Ikaros in T-cell acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    Philippe; Kastner; Susan; Chan

    2011-01-01

    Ikaros is a zinc finger transcriptional regulator encoded by the Ikzf1 gene.Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemia.In particular,Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia.Its role in T-cell leukemia,however,has been more controversial.While Ikaros deficiency appears to be very frequent in murine T-cell leukemias,loss of Ikaros appears to be rare in human T-cell acute lymphoblastic leukemia (T-ALL).We review here the evidence linking Ikaros to T-ALL in mouse and human systems.

  1. 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

  2. The target cell of transformation is distinct from the leukemia stem cell in murine CALM/AF10 leukemia models.

    Science.gov (United States)

    Dutta, S; Krause, A; Vosberg, S; Herold, T; Ksienzyk, B; Quintanilla-Martinez, L; Tizazu, B; Chopra, M; Graf, A; Krebs, S; Blum, H; Greif, P A; Vetter, A; Metzeler, K; Rothenberg-Thurley, M; Schneider, M R; Dahlhoff, M; Spiekermann, K; Zimber-Strobl, U; Wolf, E; Bohlander, S K

    2016-05-01

    The CALM/AF10 fusion gene is found in various hematological malignancies including acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia and malignant lymphoma. We have previously identified the leukemia stem cell (LSC) in a CALM/AF10-driven murine bone marrow transplant AML model as B220+ lymphoid cells with B-cell characteristics. To identify the target cell for leukemic transformation or 'cell of origin of leukemia' (COL) in non-disturbed steady-state hematopoiesis, we inserted the CALM/AF10 fusion gene preceded by a loxP-flanked transcriptional stop cassette into the Rosa26 locus. Vav-Cre-induced panhematopoietic expression of the CALM/AF10 fusion gene led to acute leukemia with a median latency of 12 months. Mice expressing CALM/AF10 in the B-lymphoid compartment using Mb1-Cre or CD19-Cre inducer lines did not develop leukemia. Leukemias had a predominantly myeloid phenotype but showed coexpression of the B-cell marker B220, and had clonal B-cell receptor rearrangements. Using whole-exome sequencing, we identified an average of two to three additional mutations per leukemia, including activating mutations in known oncogenes such as FLT3 and PTPN11. Our results show that the COL for CALM/AF10 leukemia is a stem or early progenitor cell and not a cell of B-cell lineage with a phenotype similar to that of the LSC in CALM/AF10+ leukemia. PMID:26686248

  3. Genomically intact endogenous feline leukemia viruses of recent origin.

    Science.gov (United States)

    Roca, Alfred L; Pecon-Slattery, Jill; O'Brien, Stephen J

    2004-04-01

    We isolated and sequenced two complete endogenous feline leukemia viruses (enFeLVs), designated enFeLV-AGTT and enFeLV-GGAG. In enFeLV-AGTT, the open reading frames are reminiscent of a functioning FeLV genome, and the 5' and 3' long terminal repeat sequences are identical. Neither endogenous provirus is genetically fixed in cats but polymorphic, with 8.9 and 15.2% prevalence for enFeLV-AGTT and enFeLV-GGAG, respectively, among a survey of domestic cats. Neither provirus was found in the genomes of related species of the Felis genus, previously shown to harbor enFeLVs. The absence of mutational divergence, polymorphic incidence in cats, and absence in related species suggest that these enFeLVs may have entered the germ line more recently than previously believed, perhaps coincident with domestication, and reopens the question of whether some enFeLVs might be replication competent. PMID:15047851

  4. Occurrence of Feline Immunodeficiency Virus and Feline Leukemia Virus Infection in Cats

    Directory of Open Access Journals (Sweden)

    Fabiana Alves

    2011-01-01

    Full Text Available Problem statement: The objective of the present work was to evaluate the occurrence of the Feline Immunodeficiency Virus (FIV and the Feline Leukemia Virus (FeLV infection in asymptomatic domestic cats in the metropolitan region of Belo Horizonte, Minas Gerais, using the Polymerase Chain Reaction (PCR for FIV detection and SNAP Combo Plus for FeLV and FIV detection. Approach: Blood samples were collected from the jugular vein of 78 healthy cats, mixed breeds and ages and both sexes. Specific primers were designed for PCR to amplify a 244 bp fragment of FIV gag gene. Results: Five animals (6.41% were positive by PCR and three animals (3.85% were positive by SNAP Combo Plus for FIV and 14 animals were positive for FeLV (17.95%. Conclusion: These results suggest that there is a significant occurrence of asymptomatic infected animals which may serve as potential transmitters of FIV and FeLV.

  5. Detection of Xenotropic Murine Leukemia Virus-Related Virus in Prostate Biopsy Samples

    International Nuclear Information System (INIS)

    Objective: To determine the association of Xenotropic murine leukemia virus related virus (XMRV) infection with prostate cancer and compare it with benign prostate hyperplasia. Study Design: Case control study. Place and Duration of Study: Department of Histopathology and Molecular Pathology, Dow University of Health Sciences, Karachi, from January 2009 to December 2012. Methodology: XMRV was screened in 50 prostate cancer and 50 benign prostatic hyperplasia biopsies using conventional end-point PCR. Other studied variables were family history of prostate cancer, patients age and Gleason score. Results: XMRV was detected in 4 (8%) of the 50 prostate cancer biopsy specimens compared to none in biopsies with benign prostatic hyperplasia. However, there was no significant statistical association of XMRV infection with the other variables. Conclusion: A low frequency of XMRV infection was found in this case-control study. Men, who harbor XMRV infection, may be at increased risk of prostate cancer but this needs to be investigated further at a larger scale. (author)

  6. Managing the future: the Special Virus Leukemia Program and the acceleration of biomedical research.

    Science.gov (United States)

    Scheffler, Robin Wolfe

    2014-12-01

    After the end of the Second World War, cancer virus research experienced a remarkable revival, culminating in the creation in 1964 of the United States National Cancer Institute's Special Virus Leukemia Program (SVLP), an ambitious program of directed biomedical research to accelerate the development of a leukemia vaccine. Studies of cancer viruses soon became the second most highly funded area of research at the Institute, and by far the most generously funded area of biological research. Remarkably, this vast infrastructure for cancer vaccine production came into being before a human leukemia virus was shown to exist. The origins of the SVLP were rooted in as much as shifts in American society as laboratory science. The revival of cancer virus studies was a function of the success advocates and administrators achieved in associating cancer viruses with campaigns against childhood diseases such as polio and leukemia. To address the urgency borne of this new association, the SVLP's architects sought to lessen the power of peer review in favor of centralized Cold War management methods, fashioning viruses as "administrative objects" in order to accelerate the tempo of biomedical research and discovery. PMID:25459347

  7. Hematopoietic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia

    OpenAIRE

    Ibrahim Bayram

    2014-01-01

    In children patients with acute lymphoblastic leukemia, according to the European bone marrow transplant handbook, the indications for stem cell transplantation, conditioning regimen, donor selection and information about sources of stem cells will be evaluated.

  8. The BET family of proteins targets Moloney Murine Leukemia Virus integration near transcription start sites

    Science.gov (United States)

    De Rijck, Jan; de Kogel, Christine; Demeulemeester, Jonas; Vets, Sofie; Ashkar, Sara El; Malani, Nirav; Bushman, Frederic D; Landuyt, Bart; Husson, Steven J.; Busschots, Katrien; Gijsbers, Rik; Debyser, Zeger

    2014-01-01

    Summary A hallmark of retroviral replication is integration of the viral genome in the host cell DNA. This characteristic makes retrovirus-based vectors attractive delivery vehicles for gene therapy. However, adverse events in gene therapeutic trials, caused by activation of proto-oncogenes due to Murine Leukemia Virus (MLV)-derived vector integration, hamper their application. Here we show that bromodomain and extraterminal (BET) proteins (BRD2, BRD3 and BRD4) and MLV integrase specifically interact and co-localize within the nucleus of the cell. Inhibition of the BET proteins chromatin interaction via specific bromodomain inhibitors blocks MLV virus replication at the integration step. MLV integration site distribution parallels the chromatin binding profile of BET proteins, and expression of an artificial fusion protein of the BET integrase binding domain with the chromatin interaction domain of the lentiviral targeting factor LEDGF/p75, retargets MLV integration away from TSS and into the body of actively transcribed genes, conform to the Human Immunodeficiency Virus (HIV) integration pattern. Together these data validate BET proteins as MLV integration targeting factors. PMID:24183673

  9. Allogeneic cellular immunotherapy for chronic B-cell leukemia

    OpenAIRE

    Hoogendoorn, Mels

    2007-01-01

    Allogeneic stem cell transplantation (SCT) following reduced-intensity conditioning (RIC) as treatment modality has curative potential in patients suffering from chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL), illustrating susceptibility of these leukemic cells for the graft-versus-leukemia (GvL) effect. However, effectiveness of this therapy is limited due to low immunogenicity of leukemic cells and the lack of specificity resulting in concurrent development of graft-versus...

  10. Bovine leukemia virus nucleocapsid protein is an efficient nucleic acid chaperone

    Energy Technology Data Exchange (ETDEWEB)

    Qualley, Dominic F., E-mail: dqualley@berry.edu; Sokolove, Victoria L.; Ross, James L.

    2015-03-13

    Nucleocapsid proteins (NCs) direct the rearrangement of nucleic acids to form the most thermodynamically stable structure, and facilitate many steps throughout the life cycle of retroviruses. NCs bind strongly to nucleic acids (NAs) and promote NA aggregation by virtue of their cationic nature; they also destabilize the NA duplex via highly structured zinc-binding motifs. Thus, they are considered to be NA chaperones. While most retroviral NCs are structurally similar, differences are observed both within and between retroviral genera. In this work, we compare the NA binding and chaperone activity of bovine leukemia virus (BLV) NC to that of two other retroviral NCs: human immunodeficiency virus type 1 (HIV-1) NC, which is structurally similar to BLV NC but from a different retrovirus genus, and human T-cell leukemia virus type 1 (HTLV-1) NC, which possesses several key structural differences from BLV NC but is from the same genus. Our data show that BLV and HIV-1 NCs bind to NAs with stronger affinity in relation to HTLV-1 NC, and that they also accelerate the annealing of complementary stem-loop structures to a greater extent. Analysis of kinetic parameters derived from the annealing data suggests that while all three NCs stimulate annealing by a two-step mechanism as previously reported, the relative contributions of each step to the overall annealing equilibrium are conserved between BLV and HIV-1 NCs but are different for HTLV-1 NC. It is concluded that while BLV and HTLV-1 belong to the same genus of retroviruses, processes that rely on NC may not be directly comparable. - Highlights: • BLV NC binds strongly to DNA and RNA. • BLV NC promotes mini-TAR annealing as well as HIV-1 NC. • Annealing kinetics suggest a low degree of similarity between BLV NC and HTLV-1 NC.

  11. Bovine leukemia virus nucleocapsid protein is an efficient nucleic acid chaperone

    International Nuclear Information System (INIS)

    Nucleocapsid proteins (NCs) direct the rearrangement of nucleic acids to form the most thermodynamically stable structure, and facilitate many steps throughout the life cycle of retroviruses. NCs bind strongly to nucleic acids (NAs) and promote NA aggregation by virtue of their cationic nature; they also destabilize the NA duplex via highly structured zinc-binding motifs. Thus, they are considered to be NA chaperones. While most retroviral NCs are structurally similar, differences are observed both within and between retroviral genera. In this work, we compare the NA binding and chaperone activity of bovine leukemia virus (BLV) NC to that of two other retroviral NCs: human immunodeficiency virus type 1 (HIV-1) NC, which is structurally similar to BLV NC but from a different retrovirus genus, and human T-cell leukemia virus type 1 (HTLV-1) NC, which possesses several key structural differences from BLV NC but is from the same genus. Our data show that BLV and HIV-1 NCs bind to NAs with stronger affinity in relation to HTLV-1 NC, and that they also accelerate the annealing of complementary stem-loop structures to a greater extent. Analysis of kinetic parameters derived from the annealing data suggests that while all three NCs stimulate annealing by a two-step mechanism as previously reported, the relative contributions of each step to the overall annealing equilibrium are conserved between BLV and HIV-1 NCs but are different for HTLV-1 NC. It is concluded that while BLV and HTLV-1 belong to the same genus of retroviruses, processes that rely on NC may not be directly comparable. - Highlights: • BLV NC binds strongly to DNA and RNA. • BLV NC promotes mini-TAR annealing as well as HIV-1 NC. • Annealing kinetics suggest a low degree of similarity between BLV NC and HTLV-1 NC

  12. Mutational library analysis of selected amino acids in the receptor binding domain of envelope of Akv murine leukemia virus by conditionally replication competent bicistronic vectors

    DEFF Research Database (Denmark)

    Bahrami, Shervin; Pedersen, Finn Skou; Duch, Mogens R.;

    2003-01-01

    sufficient envelope expression. This vector functions as a replication competent mini-virus in a culture of NIH 3T3 derived semi-packaging cells that express the viral Gag and Pol proteins. Titers comparable to those of wild type virus were achieved by this system. To test this vector system, we created a......The envelope protein of retroviruses is responsible for viral entry into host cells. Here, we describe a mutational library approach to dissect functional domains of the envelope protein involving a retroviral vector, which expresses both the envelope protein of Akv murine leukemia virus (MLV) and...... random mutational library of Arg 85 and Asp 86 in the first variable region of Akv envelope protein. Homologous amino acids to Asp 86 in Moloney and Friend murine leukemia viruses are thought to be directly involved in receptor binding. Subsequent selection of mutants capable of infecting murine NIH 3T3...

  13. Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells.

    Science.gov (United States)

    Kozako, Tomohiro; Soeda, Shuhei; Yoshimitsu, Makoto; Arima, Naomichi; Kuroki, Ayako; Hirata, Shinya; Tanaka, Hiroaki; Imakyure, Osamu; Tone, Nanako; Honda, Shin-Ichiro; Soeda, Shinji

    2016-05-01

    Adult T-cell leukemia/lymphoma (ATL), an aggressive T-cell malignancy that develops after long-term infection with human T-cell leukemia virus (HTLV-1), requires new treatments. Drug repositioning, reuse of a drug previously approved for the treatment of another condition to treat ATL, offers the possibility of reduced time and risk. Among clinically available angiotensin II receptor blockers, telmisartan is well known for its unique ability to activate peroxisome proliferator-activated receptor-γ, which plays various roles in lipid metabolism, cellular differentiation, and apoptosis. Here, telmisartan reduced cell viability and enhanced apoptotic cells via caspase activation in ex vivo peripheral blood monocytes from asymptomatic HTLV-1 carriers (ACs) or via caspase-independent cell death in acute-type ATL, which has a poor prognosis. Telmisartan also induced significant growth inhibition and apoptosis in leukemia cell lines via caspase activation, whereas other angiotensin II receptor blockers did not induce cell death. Interestingly, telmisartan increased the LC3-II-enriched protein fraction, indicating autophagosome accumulation and autophagy. Thus, telmisartan simultaneously caused caspase activation and autophagy. A hypertension medication with antiproliferation effects on primary and leukemia cells is intriguing. Patients with an early diagnosis of ATL are generally monitored until the disease progresses; thus, suppression of progression from AC and indolent ATL to acute ATL is important. Our results suggest that telmisartan is highly effective against primary cells and leukemia cell lines in caspase-dependent and -independent manners, and its clinical use may suppress acute transformation and improve prognosis of patients with this mortal disease. This is the first report demonstrating a cell growth-inhibitory effect of telmisartan in fresh peripheral blood mononuclear cells from leukemia patients. PMID:27419050

  14. Seroprevalence of Toxoplasma gondii and concurrent bartonella spp., feline immunodeficiency virus, and feline leukemia infections in cats from Grenada, West Indies

    Science.gov (United States)

    Toxoplasma gondii and Bartonella spp. are zoonotic pathogens of cats. Feline Immunodeficiency Virus (FIV), and Feline Leukemia Virus (FeLv) are related to Human Iimmunodeficiency Virus, and Human Leukemia Virus, respectively, and these viruses are immunosuppressive. In the present study, the prevale...

  15. Mechanisms in endogenous leukemia virus induction by radiation and chemicals

    International Nuclear Information System (INIS)

    A model of endogenous virus induction in AKR-strain mouse cells, based on two distinct types of alterations in cellular or proviral DNA, is presented. The first type are nonrepairable alterations such as those caused by the incorporation of halogenated pyrimidines; the second type are repairable lesions such as those caused by irradiation or certain chemicals other than pyrimidines. The production of nonrepairable lesions leads to the formation of a stable, proviral state which is dependent upon cell division for complete virus expression. A stable provirus intermediate state is not demonstrable in mouse cells induced by treatments which cause repairable lesions since replication of damaged or altered DNA must occur before the lesions are removed by repair synthesis. Experimental support for this model is based upon the following observations: (a) enhancement of induction is observed if lesions are introduced during cellular DNA synthesis; (b) quinacrine, which is an inhibitor of repair synthesis, increases the observed level of radiation induction; and (c) incorporation of 5-iodo-2'-deoxyuridine during repair of DNA appears to 'stabilize' lesions which would otherwise be removed by repair synthesis, and increases the level of virus induction

  16. Role of Ikaros in T-cell acute lymphoblastic leukemia

    OpenAIRE

    Kastner, Philippe; Chan, Susan

    2011-01-01

    Ikaros is a zinc finger transcriptional regulator encoded by the Ikzf1 gene. Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemia. In particular, Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia. Its role in T-cell leukemia, however, has been more controversial. While Ikaros deficiency appears to be very frequent in murine T-cell l...

  17. Identification of a novel human tRNA(Ser(CGA)) functional in murine leukemia virus replication

    DEFF Research Database (Denmark)

    Lund, Anders Henrik; Schmitz, A; Pedersen, F S;

    2000-01-01

    We have identified a human tRNA(Ser) isoacceptor matching the UCG codon. The tRNA was discovered via its ability to act in reverse transcription of a murine leukemia virus vector containing a complementary tRNA primer binding site (Lund et al., Nucleic Acids Res., 28 (2000) 791-799). The tRNA......(Ser(CGA)) was detected in cell lines of human, monkey and mouse origin. The UCG codon is the most rarely used codon in human genes. The cloned human tRNA(Ser(CGA)) gene encodes an 85 nucleotide, intron-less tRNA, contains a consensus split intragenic promoter and is located at region p21.3-22.2 on chromosome 6....... The integrity and functionality of the cloned tRNA(Ser(CGA)) gene was verified by in vitro transcription analysis in HeLa nuclear extracts....

  18. Role for protein geranylgeranylation in adult T-cell leukemia cell survival

    International Nuclear Information System (INIS)

    Adult T-cell leukemia (ATL) is a fatal lymphoproliferative disease that develops in human T-cell leukemia virus type I (HTLV-I)-infected individuals. Despite the accumulating knowledge of the molecular biology of HTLV-I-infected cells, effective therapeutic strategies remain to be established. Recent reports showed that the hydroxyl-3-methylglutaryl (HMG)-CoA reductase inhibitor statins have anti-proliferative and apoptotic effects on certain tumor cells through inhibition of protein prenylation. Here, we report that statins hinder the survival of ATL cells and induce apoptotic cell death. Inhibition of protein geranylgeranylation is responsible for these effects, since simultaneous treatment with isoprenoid precursors, geranylgeranyl pyrophosphate or farnesyl pyrophosphate, but not a cholesterol precursor squalene, restored the viability of ATL cells. Simvastatin inhibited geranylgeranylation of small GTPases Rab5B and Rac1 in ATL cells, and a geranylgeranyl transferase inhibitor GGTI-298 reduced ATL cell viability more efficiently than a farnesyl transferase inhibitor FTI-277. These results not only unveil an important role for protein geranylgeranylation in ATL cell survival, but also implicate therapeutic potentials of statins in the treatment of ATL

  19. Vitamin D Protects Acute Lymphoblastic Leukemia Cells from Dexamethasone

    OpenAIRE

    Antony, Reuben; Sheng, Xia; Ehsanipour, Ehsan A.; Ng, Emily; Pramanik, Rocky; Klemm, Lars; Ichihara, Brian; Mittelman, Steven D.

    2012-01-01

    Vitamin D deficiency has been linked with increased cancer risk, and vitamin D has been shown to be cytotoxic to some cancer cells in vitro. In the present study we evaluated whether vitamin D would have antiproliferative or cytotoxic effects on human pre-B acute lymphoblastic leukemia cells. Contrary to our hypotheses, calcitriol, the active form of vitamin D, had no effect on leukemia cell proliferation. Calcitriol actually had a modest effect to impair dexamethasone cytotoxicity and induct...

  20. Endophilins interact with Moloney murine leukemia virus Gag and modulate virion production

    Directory of Open Access Journals (Sweden)

    De Camilli Pietro

    2003-12-01

    Full Text Available Abstract Background The retroviral Gag protein is the central player in the process of virion assembly at the plasma membrane, and is sufficient to induce the formation and release of virus-like particles. Recent evidence suggests that Gag may co-opt the host cell's endocytic machinery to facilitate retroviral assembly and release. Results A search for novel partners interacting with the Gag protein of the Moloney murine leukemia virus (Mo-MuLV via the yeast two-hybrid protein-protein interaction assay resulted in the identification of endophilin 2, a component of the machinery involved in clathrin-mediated endocytosis. We demonstrate that endophilin interacts with the matrix or MA domain of the Gag protein of Mo-MuLV, but not of human immunodeficiency virus, HIV. Both exogenously expressed and endogenous endophilin are incorporated into Mo-MuLV viral particles. Titration experiments suggest that the binding sites for inclusion of endophilin into viral particles are limited and saturable. Knock-down of endophilin with small interfering RNA (siRNA had no effect on virion production, but overexpression of endophilin and, to a lesser extent, of several fragments of the protein, result in inhibition of Mo-MuLV virion production, but not of HIV virion production. Conclusions This study shows that endophilins interact with Mo-MuLV Gag and affect virion production. The findings imply that endophilin is another component of the large complex that is hijacked by retroviruses to promote virion production.

  1. Fidelity of target site duplication and sequence preference during integration of xenotropic murine leukemia virus-related virus.

    Directory of Open Access Journals (Sweden)

    Sanggu Kim

    Full Text Available Xenotropic murine leukemia virus (MLV-related virus (XMRV is a new human retrovirus associated with prostate cancer and chronic fatigue syndrome. The causal relationship of XMRV infection to human disease and the mechanism of pathogenicity have not been established. During retrovirus replication, integration of the cDNA copy of the viral RNA genome into the host cell chromosome is an essential step and involves coordinated joining of the two ends of the linear viral DNA into staggered sites on target DNA. Correct integration produces proviruses that are flanked by a short direct repeat, which varies from 4 to 6 bp among the retroviruses but is invariant for each particular retrovirus. Uncoordinated joining of the two viral DNA ends into target DNA can cause insertions, deletions, or other genomic alterations at the integration site. To determine the fidelity of XMRV integration, cells infected with XMRV were clonally expanded and DNA sequences at the viral-host DNA junctions were determined and analyzed. We found that a majority of the provirus ends were correctly processed and flanked by a 4-bp direct repeat of host DNA. A weak consensus sequence was also detected at the XMRV integration sites. We conclude that integration of XMRV DNA involves a coordinated joining of two viral DNA ends that are spaced 4 bp apart on the target DNA and proceeds with high fidelity.

  2. Relationship between endogenous ecotropic murine leukemia virus and radiation leukemogenesis in various strains of mice

    International Nuclear Information System (INIS)

    The relationship between the incidence of radiation-induced leukemia and replication of infectious ecotropic leukemia virus was investigated using RF, BALB/c, NIH Swiss and DD/Tb mice. Mice of all strains tested have been shown to be highly susceptible to the induction of thymic lymphoma of fractionated whole-body x-irradiation. The replication of endogenous ecotropic MuLV in RF and BALB/c mice was enhanced by x-irradiation. On the contrary, any infectious ecotropic virus could not be detected in NIH Swiss and DD/Tb mice. (auth.)

  3. Characterization of mouse cellular deoxyribonucleic acid homologous to Abelson murine leukemia virus-specific sequences.

    OpenAIRE

    Dale, B.; Ozanne, B.

    1981-01-01

    The genome of Abelson murine leukemia virus (A-MuLV) consists of sequences derived from both BALB/c mouse deoxyribonucleic acid and the genome of Moloney murine leukemia virus. Using deoxyribonucleic acid linear intermediates as a source of retroviral deoxyribonucleic acid, we isolated a recombinant plasmid which contained 1.9 kilobases of the 3.5-kilobase mouse-derived sequences found in A-MuLV (A-MuLV-specific sequences). We used this clone, designated pSA-17, as a probe restriction enzyme ...

  4. CELLULAR AND MOLECULAR BASIS OF HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE SUCCESSFUL TREATMENT OF HIGH RISK LEUKEMIAS.

    Directory of Open Access Journals (Sweden)

    FRANCO eLOCATELLI

    2013-02-01

    Full Text Available Natural Killer (NK cells are involved in innate immune responses and play a major role in tumor surveillance and in defence against viruses. Human NK cells recognize HLA-class I molecules via surface receptors (KIR and NKG2A delivering signals that inhibit NK cell function and kill HLA-class I-deficient target cells, a frequent event in tumors or virus-infected cells. NK cell triggering is mediated by activating receptors that recognize ligands expressed primarily on tumors or virus-infected cells. NK cells play also a key role in the cure of high-risk leukemias. Thus, donor-derived alloreactive NK cells are fundamental effectors in adult acute myeloid leukemia (AML and in pediatric acute lymphoblastic leukemia (ALL patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT. Alloreactive NK cells mediate killing of leukemia cells and patient’s DC, thus preventing respectively leukemic relapses and graft-versus-host responses. FACS analysis of KIRs expressed by NK cells allows to define the size of the alloreactive NK subset and the selection of the best potential donor. Recently, it has been shown that also the expression of activating KIRs, in particular the (C2-specific KIR2DS1, may contribute to donor NK alloreactivity. It has also been established a correlation between the size of the alloreactive NK cell population and the clinical outcome. Notably, the alloreactive NK cells derived from donor’s HSC are generated and persist in patients over time. The high survival rates of patients undergoing haploidentical HSCT highlight an important new reality in the setting of allograft performed to cure otherwise fatal leukemias. Novel approaches are in progress to further improve the clinical outcome based on the infusion of donor alloreactive NK cells either as a component of the transplanted cell population or as in vitro expanded NK cells.

  5. Structural and biochemical characterization of the inhibitor complexes of xenotropic murine leukemia virus-related virus protease

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mi; Gustchina, Alla; Matúz, Krisztina; Tözsér, Jozsef; Namwong, Sirilak; Goldfarb, Nathan E.; Dunn, Ben M.; Wlodawer, Alexander (Debrecen); (NCI); (Florida); (Suan Sunandha)

    2012-10-23

    Interactions between the protease (PR) encoded by the xenotropic murine leukemia virus-related virus and a number of potential inhibitors have been investigated by biochemical and structural techniques. It was observed that several inhibitors used clinically against HIV PR exhibit nanomolar or even subnanomolar values of K{sub i}, depending on the exact experimental conditions. Both TL-3, a universal inhibitor of retroviral PRs, and some inhibitors originally shown to inhibit plasmepsins were also quite potent, whereas inhibition by pepstatin A was considerably weaker. Crystal structures of the complexes of xenotropic murine leukemia virus-related virus PR with TL-3, amprenavir and pepstatin A were solved at high resolution and compared with the structures of complexes of these inhibitors with other retropepsins. Whereas TL-3 and amprenavir bound in a predictable manner, spanning the substrate-binding site of the enzyme, two molecules of pepstatin A bound simultaneously in an unprecedented manner, leaving the catalytic water molecule in place.

  6. Genome-wide association study for host response to bovine leukemia virus in Holstein cows.

    Science.gov (United States)

    Brym, P; Bojarojć-Nosowicz, B; Oleński, K; Hering, D M; Ruść, A; Kaczmarczyk, E; Kamiński, S

    2016-07-01

    The mechanisms of leukemogenesis induced by bovine leukemia virus (BLV) and the processes underlying the phenomenon of differential host response to BLV infection still remain poorly understood. The aim of the study was to screen the entire cattle genome to identify markers and candidate genes that might be involved in host response to bovine leukemia virus infection. A genome-wide association study was performed using Holstein cows naturally infected by BLV. A data set included 43 cows (BLV positive) and 30 cows (BLV negative) genotyped for 54,609 SNP markers (Illumina Bovine SNP50 BeadChip). The BLV status of cows was determined by serum ELISA, nested-PCR and hematological counts. Linear Regression Analysis with a False Discovery Rate and kinship matrix (computed on the autosomal SNPs) was calculated to find out which SNP markers significantly differentiate BLV-positive and BLV-negative cows. Nine markers reached genome-wide significance. The most significant SNPs were located on chromosomes 23 (rs41583098), 3 (rs109405425, rs110785500) and 8 (rs43564499) in close vicinity of a patatin-like phospholipase domain containing 1 (PNPLA1); adaptor-related protein complex 4, beta 1 subunit (AP4B1); tripartite motif-containing 45 (TRIM45) and cell division cycle associated 2 (CDCA2) genes, respectively. Furthermore, a list of 41 candidate genes was composed based on their proximity to significant markers (within a distance of ca. 1 Mb) and functional involvement in processes potentially underlying BLV-induced pathogenesis. In conclusion, it was demonstrated that host response to BLV infection involves nine sub-regions of the cattle genome (represented by 9 SNP markers), containing many genes which, based on the literature, could be involved to enzootic bovine leukemia progression. New group of promising candidate genes associated with the host response to BLV infection were identified and could therefore be a target for future studies. The functions of candidate genes

  7. An Aromatic Side Chain Is Required at Residue 8 of SU for Fusion of Ecotropic Murine Leukemia Virus

    OpenAIRE

    Qian, Zhaohui; Albritton, Lorraine M.

    2004-01-01

    The surface glycoprotein (SU) of most gammaretroviruses contains a conserved histidine at its amino terminus. In ecotropic murine leukemia virus SU, replacement of histidine 8 with arginine (H8R) or deletion of H8 (H8del) abolishes infection and cell-cell fusion but has no effect on binding to the cellular receptor. We report here that an aromatic ring side chain is essential to the function of residue 8. The size of the aromatic ring appears to be important, as does its ability to form a hyd...

  8. Therapeutic Effects of Myeloid Cell Leukemia-1 siRNA on Human Acute Myeloid Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Hadi Karami

    2014-05-01

    Full Text Available Purpose: Up-regulation of Mcl-1, a known anti-apoptotic protein, is associated with the survival and progression of various malignancies including leukemia. The aim of this study was to explore the effect of Mcl-1 small interference RNA (siRNA on the proliferation and apoptosis of HL-60 acute myeloid leukemia (AML cells. Methods: siRNA transfection was performed using Lipofectamine™2000 reagent. Relative mRNA and protein expressions were quantified by quantitative real-time PCR and Western blotting, respectively. Trypan blue assay was performed to assess tumor cell proliferation after siRNA transfection. The cytotoxic effect of Mcl-1 siRNA on leukemic cells was measured using MTT assay. Apoptosis was detected using ELISA cell death assay. Results: Mcl-1 siRNA clearly lowered both Mcl-1 mRNA and protein levels in a time-dependent manner, leading to marked inhibition of cell survival and proliferation. Furthermore, Mcl-1 down-regulation significantly enhanced the extent of HL-60 apoptotic cells. Conclusion: Our results suggest that the down-regulation of Mcl-1 by siRNA can effectively trigger apoptosis and inhibit the proliferation of leukemic cells. Therefore, Mcl-1 siRNA may be a potent adjuvant in AML therapy.

  9. BRAF mutation in hairy cell leukemia

    Directory of Open Access Journals (Sweden)

    Ahmad Ahmadzadeh

    2014-09-01

    Full Text Available BRAF is a serine/threonine kinase with a regulatory role in the mitogen-activated protein kinase (MAPK signaling pathway. A mutation in the RAF gene, especially in BRAF protein, leads to an increased stimulation of this cascade, causing uncontrolled cell division and development of malignancy. Several mutations have been observed in the gene coding for this protein in a variety of human malignancies, including hairy cell leukemia (HCL. BRAF V600E is the most common mutation reported in exon15 of BRAF, which is observed in almost all cases of classic HCL, but it is negative in other B-cell malignancies, including the HCL variant. Therefore it can be used as a marker to differentiate between these B-cell disorders. We also discuss the interaction between miRNAs and signaling pathways, including MAPK, in HCL. When this mutation is present, the use of BRAF protein inhibitors may represent an effective treatment. In this review we have evaluated the role of the mutation of the BRAF gene in the pathogenesis and progression of HCL.

  10. In vitro radiosensitivity of human leukemia cell lines

    International Nuclear Information System (INIS)

    The in vitro radiobiologic survival values (n, D0) of four tumor lines derived from human hematopoietic tumors were studied. These cell lines were HL50 (n . 1.3, D0 . 117 rad[1.17 Gy]), promyelocytic leukemia; K562 (n . 1.4, D0 . 165 rad[1.65 Gy]), erythroleukemia; 45 (n . 1.1, D0 . 147 rad[1.47 Gy]), acute lymphocyte leukemia; and 176 (n . 4.0, D0 . 76 rad[0.76 Gy]), acute monomyelogenous leukemia. More cell lines must be examined before the exact relationship between in vitro radiosensitivity and clinical radiocurability is firmly established

  11. Treating Multiply Relapsed or Refractory Hairy Cell Leukemia

    Science.gov (United States)

    In this trial, patients with hairy cell leukemia who have not responded or relapsed after initial chemotherapy will be randomly assigned to receive rituximab combined with either pentostatin or bendamustine.

  12. Wild mouse ecotropic murine leukemia virus infection of inbred mice: dual-tropic virus expression precedes the onset of paralysis and lymphoma.

    OpenAIRE

    Hoffman, P M; Davidson, W F; Ruscetti, S K; Chused, T M; Morse, H C

    1981-01-01

    NFS/N mice inoculated at birth with an ecotropic murine leukemia virus (Cas-Br-MuLV) obtained from wild mice developed hind limb paralysis beginning at 7 weeks of age and nonthymic lymphomas beginning at more than 20 weeks of age. Studies of 1- to 7-week-old Cas-Br-M MuLV-infected mice showed the following: (i) a marked increase in nonecotropic MuLV-related antigens on spleen cells but not thymocytes beginning at 2 weeks; (ii) the appearance of dual-tropic mink cell focus-forming (MCF) MuLV-r...

  13. Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients

    OpenAIRE

    Xian-Ming Mo; Hong Xu; Ting-Ting Zeng; Neng-Gang Jiang; Yong-Qian Jia; Jing-Tao Dong; Jian-Hua Yu; Wen-Tong Meng

    2013-01-01

    Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development, including IL-7R alpha (CD127), cytoplasmic CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Anal...

  14. T- cell prolymphocytic leukemia - A rare case

    Directory of Open Access Journals (Sweden)

    Ghosh Sharmila

    2005-01-01

    Full Text Available T- cell Prolymhocytic leukemia (T-PLL is a rare mature post-thymic T-cell malignancy that is usually reported in the elderly and follows an aggressive course. A 68 year old male presented with a history of weakness and weight loss of two months duration. Clinical examination revealed pallor, enlarged cervical and axillary lymph nodes and splenomegaly. He also had a maculo- papular skin rash. There was marked leucocytosis, anemia and thrombocytopenia (WBC 445 x103sub/ml, Hb 8.5gm/dl, Platelet 25x103/µl with 60% prolymphocytes in the peripheral blood. Bone marrow was hypercellular with an excess of prolymphocytes. Flow cytometric analysis of the bone marrow showed positivity for CD2, CD3, CD4, CD5 and CD7. T- PLL is a rare T cell disorder with characteristic clinical and laboratory features.Currently, no optimal treatment exists although there has been some success with 2′- deoxycoformycin or Campath-1H

  15. The BET Family of Proteins Targets Moloney Murine Leukemia Virus Integration near Transcription Start Sites

    Directory of Open Access Journals (Sweden)

    Jan De Rijck

    2013-11-01

    Full Text Available A hallmark of retroviral replication is integration of the viral genome into host cell DNA. This characteristic makes retrovirus-based vectors attractive delivery vehicles for gene therapy. However, adverse events in gene therapeutic trials, caused by activation of proto-oncogenes due to murine leukemia virus (MLV-derived vector integration, hamper their application. Here, we show that bromodomain and extraterminal (BET proteins (BRD2, BRD3, and BRD4 and MLV integrase specifically interact and colocalize within the nucleus of the cell. Inhibition of the BET proteins’ chromatin interaction via specific bromodomain inhibitors blocks MLV virus replication at the integration step. MLV integration site distribution parallels the chromatin binding profile of BET proteins, and expression of an artificial fusion protein of the BET integrase binding domain with the chromatin interaction domain of the lentiviral targeting factor LEDGF/p75 retargets MLV integration away from transcription start sites and into the body of actively transcribed genes, conforming to the HIV integration pattern. Together, these data validate BET proteins as MLV integration targeting factors.

  16. Replication and pathogenicity of primer binding site mutants of SL3-3 murine leukemia viruses

    DEFF Research Database (Denmark)

    Lund, Anders Henrik; Schmidt, J; Luz, A;

    1999-01-01

    Retroviral reverse transcription is primed by a cellular tRNA molecule annealed to an 18-bp primer binding site sequence. The sequence of the primer binding site coincides with that of a negatively acting cis element that mediates transcriptional silencing of murine leukemia virus (MLV) in...... undifferentiated embryonic cells. In this study we test whether SL3-3 MLV can replicate stably using tRNA primers other than the cognate tRNAPro and analyze the effect of altering the primer binding site sequence to match the 3' end of tRNA1Gln, tRNA3Lys, or tRNA1,2Arg in a mouse pathogenicity model. Contrary to...... findings from cell culture studies of primer binding site-modified human immunodeficiency virus type 1 and avian retroviruses, our findings were that SL3-3 MLV may stably and efficiently replicate with tRNA primers other than tRNAPro. Although lymphoma induction of the SL3-3 Lys3 mutant was significantly...

  17. PCR and serology find no association between xenotropic murine leukemia virus-related virus (XMRV and autism

    Directory of Open Access Journals (Sweden)

    Satterfield Brent C

    2010-10-01

    Full Text Available Abstract Xenotropic murine leukemia virus-related virus (XMRV is a retrovirus implicated in prostate cancer and chronic fatigue syndrome (CFS. Press releases have suggested that it could contribute to autism spectrum disorder (ASD. In this study we used two PCR assays and one antibody assay to screen 25 blood samples from autistic children born to mothers with CFS and from 20 mixed controls including family members of the children assayed, people with fibromyalgia and people with chronic Lyme disease. Using a real-time PCR assay, we screened an additional 48 South Carolina autism disorder samples, 96 Italian ASD samples, 61 South Carolina ASD samples and 184 healthy controls. Despite having the ability to detect low copy number XMRV DNA in a large background of cellular DNA, none of the PCR assays found any evidence of XMRV infection in blood cells from patients or controls. Further, no anti-XMRV antibodies were detected, ruling out possible low level or abortive infections in blood or in other reservoirs. These results imply that XMRV is not associated with autism.

  18. Lapatinib induces autophagic cell death and differentiation in acute myeloblastic leukemia

    Directory of Open Access Journals (Sweden)

    Chen YJ

    2016-07-01

    Full Text Available Yu-Jen Chen,1–4 Li-Wen Fang,5 Wen-Chi Su,6,7 Wen-Yi Hsu,1 Kai-Chien Yang,1 Huey-Lan Huang8 1Department of Medical Research, 2Department of Radiation Oncology, Mackay Memorial Hospital, 3Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 4Institute of Pharmacology, Taipei Medical University, Taipei, 5Department of Nutrition, I-Shou University, Kaohsiung, 6Research Center for Emerging Viruses, China Medical University Hospital, 7Graduate Institute of Clinical Medical Science, China Medical University, Taichung, 8Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan, Taiwan, Republic of China Abstract: Lapatinib is an oral-form dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR or ErbB/Her superfamily members with anticancer activity. In this study, we examined the effects and mechanism of action of lapatinib on several human leukemia cells lines, including acute myeloid leukemia (AML, chronic myeloid leukemia (CML, and acute lymphoblastic leukemia (ALL cells. We found that lapatinib inhibited the growth of human AML U937, HL-60, NB4, CML KU812, MEG-01, and ALL Jurkat T cells. Among these leukemia cell lines, lapatinib induced apoptosis in HL-60, NB4, and Jurkat cells, but induced nonapoptotic cell death in U937, K562, and MEG-01 cells. Moreover, lapatinib treatment caused autophagic cell death as shown by positive acridine orange staining, the massive formation of vacuoles as seen by electronic microscopy, and the upregulation of LC3-II, ATG5, and ATG7 in AML U937 cells. Furthermore, autophagy inhibitor 3-methyladenine and knockdown of ATG5, ATG7, and Beclin-1 using short hairpin RNA (shRNA partially rescued lapatinib-induced cell death. In addition, the induction of phagocytosis and ROS production as well as the upregulation of surface markers CD14 and CD68 was detected in lapatinib-treated U937 cells, suggesting the induction of

  19. Frequency and significance of feline leukemia virus infection in necropsied cats.

    Science.gov (United States)

    Reinacher, M; Theilen, G

    1987-06-01

    Feline leukemia virus (FeLV) infection was diagnosed immunohistologically on paraffin-embedded tissues obtained from 1,095 necropsied cats. Significant association of FeLV infection was demonstrated by chi 2 and Fisher's tests with various conditions and diseases (ie, anemia, tumors of the leukemia/lymphoma complex, feline infectious peritonitis, bacterial infections, emaciation, FeLV-associated enteritis, lymphatic hyperplasia, and hemorrhage). Unexpected findings associated with FeLV infection were icterus, several types of hepatitis, and liver degeneration. A negative association with FeLV infection was found for most parasitic and viral infections, including feline panleukopenia. Neither positive nor negative associations were established for FeLV infection and most forms of nephritis, including severe glomerulonephritis. Feline leukemia virus-infected cats were significantly (Kruskal-Wallis test) older than were FeLV-negative cats with the same nonneoplastic FeLV-associated diseases. PMID:3037951

  20. Transgene stability for three replication-competent murine leukemia virus vectors

    DEFF Research Database (Denmark)

    Duch, Mogens R.; Carrasco, Maria L; Hansen, Bettina Dencker;

    2004-01-01

    cassette consisting of an internal ribosome entry site followed by the enhanced green fluorescent protein coding sequence inserted in different configurations into murine leukemia virus genomes. In two of the constructs, the insert was located in the upstream part of the U3 region while in the third...

  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. Subacute herpes simplex virus type 1 encephalitis as an initial presentation of chronic lymphocytic leukemia and multiple sclerosis: a case report

    Directory of Open Access Journals (Sweden)

    Corman Lourdes C

    2011-02-01

    Full Text Available Abstract Introduction Herpes simplex virus type 1 encephalitis presents acutely in patients who are immunocompetent. We report what we believe to be the first published case of a subacute course of herpes simplex virus type 1 encephalitis in a patient with asymptomatic chronic lymphocytic leukemia who subsequently developed multiple sclerosis. Case presentation A 49-year-old Caucasian woman with a history of fever blisters presented to the emergency department with a history of left temporal headache for four weeks, and numbness of the left face and leg for two weeks. A complete blood count revealed white blood cell count of 11,820 cells/mL, with an absolute lymphocyte count of 7304 cells/mL. The cerebrospinal fluid contained 6 white blood cells/μL, 63 red blood cells/μL, 54 mg glucose/dL, and 49 mg total protein/dL. Magnetic resonance imaging of the brain revealed meningoencephalitis and bilateral ventriculitis. Cerebrospinal fluid polymerase chain reaction for herpes simplex virus type 1 was positive, and the patient's symptoms resolved after ten days of treatment with parenteral aciclovir. Incidental findings on peripheral blood smear and flow cytometry testing confirmed chronic lymphocytic leukemia. One month later, she developed bilateral numbness of the hands and feet; a repeat cerebrospinal fluid polymerase chain reaction for herpes simplex virus type 1 at this time was negative. A repeat magnetic resonance imaging scan showed an expansion of the peri-ventricular lesions, and the cerebrospinal fluid contained elevated oligoclonal bands and myelin basic protein. A brain biopsy revealed gliosis consistent with multiple sclerosis, and the patient responded to treatment with high-dose parenteral steroids. Conclusion Herpes simplex virus type 1 encephalitis is a rare presentation of chronic lymphocytic leukemia. Our patient had an atypical, subacute course, presumably due to immunosuppression from chronic lymphocytic leukemia. This unusual

  3. A Unique Hairy Cell Leukemia Variant.

    Science.gov (United States)

    Jian, Charles; Hsia, Cyrus C

    2016-01-01

    A 65-year-old woman presented with easy bruising, left upper quadrant pain, decreased appetite, and weight loss. She had splenomegaly and lymphocytosis (lymphocyte count of 11.6 × 10(9)/l), with remarkably abnormal appearing morphology. Her hemoglobin and platelet counts were normal. Peripheral blood flow cytometry revealed a monoclonal B-cell population expressing CD11c, CD25, CD19, CD20, and CD103. An initial diagnosis of hairy cell leukemia (HCL) was made, and the patient was treated with a standard 5-day course of cladribine. However, her lymphocytosis improved transiently, with a relapse 4 months later. There was no improvement in her splenomegaly. An HCL variant (HCL-v) was considered based on her resistance to treatment with a purine nucleoside analog. A subsequent splenectomy improved symptoms. Two years after, the patient suffered a relapse and underwent 6 cycles of CHOP-R (cyclophosphamide, hydroxydaunomycin, oncovin, prednisone, and rituximab), achieving partial remission. While under observation, she progressed with lymphocytosis 6 months later and was treated with pentostatin. There was no significant improvement in her disease, and she died 8 weeks following treatment initiation. HCL-v is a clinically more aggressive mature B-cell lymphoma than HCL with worse splenomegaly, higher lymphocyte counts, and resistance to typical HCL therapy with purine nucleoside analogs. Early recognition of HCL-v in the history, physical examination, and investigations with morphology and flow cytometry is key to patient management. Further, as in our case of HCL-v, cell morphology can be distinctly atypical, with large nucleoli and extremely convoluted nuclei. The distinction between HCL and HCL-v is important as HCL-v patients require more aggressive therapy and closer follow-up. PMID:27462230

  4. Mutations that abrogate transactivational activity of the feline leukemia virus long terminal repeat do not affect virus replication

    International Nuclear Information System (INIS)

    The U3 region of the LTR of oncogenic Moloney murine leukemia virus (Mo-MuLV) and feline leukemia viruses (FeLV) have been previously reported to activate expression of specific cellular genes in trans, such as MHC class I, collagenase IV, and MCP-1, in an integration-independent manner. It has been suggested that transactivation of these specific cellular genes by leukemia virus U3-LTR may contribute to the multistage process of leukemogenesis. The U3-LTR region, necessary for gene transactivational activity, also contains multiple transcription factor-binding sites that are essential for normal virus replication. To dissect the promoter activity and the gene transactivational activity of the U3-LTR, we conducted mutational analysis of the U3-LTR region of FeLV-A molecular clone 61E. We identified minimal nucleotide substitution mutants on the U3 LTR that did not disturb transcription factor-binding sites but abrogated its ability to transactivate the collagenase gene promoter. To determine if these mutations actually have altered any uncharacterized important transcription factor-binding site, we introduced these U3-LTR mutations into the full-length infectious molecular clone 61E. We demonstrate that the mutant virus was replication competent but could not transactivate cellular gene expression. These results thus suggest that the gene transactivational activity is a distinct property of the LTR and possibly not related to its promoter activity. The cellular gene transactivational activity-deficient mutant FeLV generated in this study may also serve as a valuable reagent for testing the biological significance of LTR-mediated cellular gene activation in the tumorigenesis caused by leukemia viruses

  5. Epstein-Barr virus DNA load in chronic lymphocytic leukemia is an independent predictor of clinical course and survival

    OpenAIRE

    Visco, Carlo; Falisi, Erika; Young, Ken H; Pascarella, Michela; Perbellini, Omar; Carli, Giuseppe; Novella, Elisabetta; Rossi, Davide; Giaretta, Ilaria; Cavallini, Chiara; Scupoli, Maria Teresa; De Rossi, Anita; D'Amore, Emanuele Stefano Giovanni; Rassu, Mario; Gaidano, Gianluca

    2015-01-01

    The relation between Epstein-Barr virus (EBV) DNA load and clinical course of patients with chronic lymphocytic leukemia (CLL) is unknown. We assessed EBV DNA load by quantitative PCR at CLL presentation in mononuclear cells (MNC) of 220 prospective patients that were enrolled and followed-up in two major Institutions. In 20 patients EBV DNA load was also assessed on plasma samples. Forty-one age-matched healthy subjects were tested for EBV DNA load on MNC. Findings were validated in an indep...

  6. CML Mouse Model Generated from Leukemia Stem Cells.

    Science.gov (United States)

    Hu, Yiguo

    2016-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder with a high number of well-differentiated neutrophils in peripheral blood and myeloid cells in bone marrow (BM). CML is derived from the hematopoietic stem cells (HSCs) with the Philadelphia chromosome (Ph(+), t(9;22)-(q34;q11)), resulting in generating a fusion oncogene, BCR/ABL1. HSCs with Ph(+) are defined as leukemia stem cells (LSCs), a subpopulation cell at the apex of hierarchies in leukemia cells and responsible for the disease continuous propagation. Several kinds of CML models have been developed to reveal the mechanism of CML pathogenesis and evaluate therapeutic drugs in the past three decades. Here, we describe the procedures to generate a CML mouse model by introducing BCR/ABL1 into Lin(-)Sca1(+) cKit(+) population cells purified from mouse bone marrow. In CML retroviral transduction/transplantation mouse models, this modified model can mimic CML pathogenesis on high fidelity. PMID:27581136

  7. Quantitation of specific antibodies bound to feline leukemia virus in the plasma of pet cats.

    Science.gov (United States)

    Snyder, H W; Singhal, M C; Yoshida, L H; Jones, F R

    1985-08-01

    A method is described for determining levels of circulating immune complexes (CIC) composed of feline leukemia virus (FeLV) antigens and corresponding antibodies in plasma of persistently-infected pet cats. The procedure is based on the ability of high-titered heterologous anti-FeLV serum to chase cat anti-FeLV IgG from dissociated CIC by successfully competing for binding of free antigen. The eluted cat antibody is then collected and quantitated. In a study of cats in the process of clearing persistent FeLV infections, measured levels of FeLV-specific CIC correlated well with fluctuating levels of free FeLV antigen and antibody. The Raji cell assay for CIC in those cats was of comparatively little value in following the clearance of the virus, presumably because that assay does not distinguish between CIC containing viral and those containing non-viral antigens. The method described can be adapted to studies of specific immune complexes associated with a variety of syndromes, provided that the antigen eliciting the immune response is known. PMID:2995795

  8. Comprehensive mapping of receptor-functioning domains in feline leukemia virus subgroup C receptor FLVCR1.

    Science.gov (United States)

    Brown, Jennifer K; Fung, Claire; Tailor, Chetankumar S

    2006-02-01

    Infection of cells by the highly anemogenic feline leukemia virus subgroup C (FeLV-C) is mediated by the heme exporter FLVCR1, a cell surface protein containing 12 potential transmembrane segments with six presumptive extracellular loops (ECLs). To identify FLVCR1 residues critical for mediating FeLV-C infection, we first independently isolated a human cDNA encoding the FLVCR2 protein that shares 52% identity to human FLVCR1, and we show that FLVCR2 does not function as a receptor for FeLV-C. Then, by generating specific hybrids between FLVCR1 and FLVCR2 and testing susceptibility of mouse cells expressing these hybrids to beta-galactosidase encoding FeLV-C, we identify FLVCR1 ECLs 1 and 6 as critical for mediating FeLV-C infection. Mouse cells expressing a hybrid protein containing FLVCR2 backbone with the ECL6 sequence from FLVCR1 were highly susceptible to FeLV-C infection. Using site-directed mutagenesis, we show that a single mutation of Asn463 in FLVCR2 ECL6 to an acidic Asp residue (a residue present in the corresponding position 487 in FLVCR1 ECL6) is sufficient to render FLVCR2 functional as an FeLV-C receptor. However, an Asp487Asn mutation in FLVCR1 ECL6 or substitution of the entire FLVCR1 ECL6 sequence for FLVCR2 ECL6 sequence does not disrupt receptor function. Subsequent substitutions show that residues within FLVCR1 ECL1 also contribute to mediating FeLV-C infection. Furthermore, our results suggest that FLVCR1 regions that mediate FeLV-C surface unit binding are distinct from ECL1 and ECL6. Our results are consistent with previous conclusions that infection of cells by gammaretroviruses involves interaction of virus with multiple receptor regions. PMID:16439531

  9. Determinants of the Bovine Leukemia Virus Envelope Glycoproteins Involved in Infectivity, Replication and Pathogenesis

    Science.gov (United States)

    de Brogniez, Alix; Mast, Jan; Willems, Luc

    2016-01-01

    Interaction of viral envelope proteins with host cell membranes has been extensively investigated in a number of systems. However, the biological relevance of these interactions in vivo has been hampered by the absence of adequate animal models. Reverse genetics using the bovine leukemia virus (BLV) genome highlighted important functional domains of the envelope protein involved in the viral life cycle. For example, immunoreceptor tyrosine-based activation motifs (ITAM) of the envelope transmembrane protein (TM) are essential determinants of infection. Although cell fusion directed by the aminoterminal end of TM is postulated to be essential, some proviruses expressing fusion-deficient envelope proteins unexpectedly replicate at wild-type levels. Surprisingly also, a conserved N-linked glycosylation site of the extracellular envelope protein (SU) inhibits cell-to-cell transmission suggesting that infectious potential has been limited during evolution. In this review, we summarize the knowledge pertaining to the BLV envelope protein in the context of viral infection, replication and pathogenesis. PMID:27023592

  10. Determinants of the Bovine Leukemia Virus Envelope Glycoproteins Involved in Infectivity, Replication and Pathogenesis

    Directory of Open Access Journals (Sweden)

    Alix de Brogniez

    2016-03-01

    Full Text Available Interaction of viral envelope proteins with host cell membranes has been extensively investigated in a number of systems. However, the biological relevance of these interactions in vivo has been hampered by the absence of adequate animal models. Reverse genetics using the bovine leukemia virus (BLV genome highlighted important functional domains of the envelope protein involved in the viral life cycle. For example, immunoreceptor tyrosine-based activation motifs (ITAM of the envelope transmembrane protein (TM are essential determinants of infection. Although cell fusion directed by the aminoterminal end of TM is postulated to be essential, some proviruses expressing fusion-deficient envelope proteins unexpectedly replicate at wild-type levels. Surprisingly also, a conserved N-linked glycosylation site of the extracellular envelope protein (SU inhibits cell-to-cell transmission suggesting that infectious potential has been limited during evolution. In this review, we summarize the knowledge pertaining to the BLV envelope protein in the context of viral infection, replication and pathogenesis.

  11. Primary Plasma Cell Leukemia: Identity Card 2016.

    Science.gov (United States)

    Musto, Pellegrino; Simeon, Vittorio; Todoerti, Katia; Neri, Antonino

    2016-04-01

    Primary plasma cell leukemia (PPCL) is an aggressive and rare variant of multiple myeloma (MM), characterized by peculiar adverse clinical and biological features. Though the poor outcome of PPCL has been slightly improved by novel treatments during the last 10 years, due to the limited number of available studies in this uncommon disease, optimal therapy remains a classic unmet clinical need. Anyway, in the real-life practice, induction with a bortezomib-based three-drug combination, including dexamethasone and, possibly, lenalidomide, or, alternatively, thalidomide, cyclophosphamide, or doxorubicin, is a reasonable first-line option. This approach may be particularly advisable for patients with adverse cytogenetics, hyperleucocytosis, and rapidly progressive disease, in whom a fast response is required, or for those with suboptimal renal function, where, however, lenalidomide should be used with caution until renal activity is restored. In younger subjects, leukemia/lymphoma-like more intensive regimens, including hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone or continue-infusion cisplatin, doxorubicin, cyclophosphamide, and etoposide, may be also combined with bortezomib +/- thalidomide. Treatment must be started immediately after a diagnosis of PPCL is made to avoid the risk of irreversible disease complications and, in such a context, the prevention of tumor lysis syndrome is mandatory. In patients eligible for autologous stem cell transplantation (AuSCT), other alkylating agents, in particular melphalan, should be initially avoided in order to allow adequate collections of CD34+ peripheral blood stem cells (PBSC). A combination of lenalidomide and dexamethasone may be a valuable alternative option to manage older or unfit patients or those with slower disease evolution or with signs of neuropathy, contraindicating the use of bortezomib. Patients not suitable for transplant procedures should continue the treatment, if a

  12. [Hypercalcemia of T-cell leukemia in adults].

    Science.gov (United States)

    Jean-Baptiste, G; Arfi, S; Plumelle, Y; Panelatti, G; Mangin, J L; Pascaline, N

    1993-04-01

    A retrospective study of 26 adults with acute T-cell leukemia showed that 14 patients (54%) had hypercalcemia at some point of the disease. Hypercalcemia was found at presentation in nine patients and revealed the disease in one. Eight patients had hypercalcemia at the time of death. Serum phosphorus and parathyroid hormone levels were normal. All patients with hypercalcemia tested positive for the HTLV-1 by Elisa and Western blot. Six patients had focalized or diffuse lytic roentgenographic bone lesions. Hypercalcemia in acute T-cell leukemia may involve production of interleukin-1-alpha and parathyroid hormone-related protein by HTLV-1-infected cells. PMID:8167627

  13. Inhibition of poly(ADP-ribose) polymerase 1 protects against acute myeloid leukemia by suppressing the myeloproliferative leukemia virus oncogene

    OpenAIRE

    Wang, Lingbo; Cai, Weili; Zhang, Wei; Chen, Xueying; Dong, Wenqian; Tang, Dongqi; Zhang, Yun; Ji, Chunyan; Zhang, Mingxiang

    2015-01-01

    An abnormal expression of poly(ADP-ribose) polymerase 1 (PARP-1) has been described in many tumors. PARP-1 promotes tumorigenesis and cancer progression by acting on different molecular pathways. PARP-1 inhibitors can be used with radiotherapy or chemotherapy to enhance the susceptibility of tumor cells to the treatment. However, the specific mechanism of PARP-1 in acute myeloid leukemia (AML) remains unknown. Our study showed that expression of PARP-1 was upregulated in AML patients. PARP-1 ...

  14. Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus infection

    Directory of Open Access Journals (Sweden)

    Okagawa Tomohiro

    2012-05-01

    Full Text Available Abstract The immunoinhibitory receptor T cell immunoglobulin domain and mucin domain-3 (Tim-3 and its ligand, galectin-9 (Gal-9, are involved in the immune evasion mechanisms for several pathogens causing chronic infections. However, there is no report concerning the role of Tim-3 in diseases of domestic animals. In this study, cDNA encoding for bovine Tim-3 and Gal-9 were cloned and sequenced, and their expression and role in immune reactivation were analyzed in bovine leukemia virus (BLV-infected cattle. Predicted amino acid sequences of Tim-3 and Gal-9 shared high homologies with human and mouse homologues. Functional domains, including tyrosine kinase phosphorylation motif in the intracellular domain of Tim-3 were highly conserved among cattle and other species. Quantitative real-time PCR analysis showed that bovine Tim-3 mRNA is mainly expressed in T cells such as CD4+ and CD8+ cells, while Gal-9 mRNA is mainly expressed in monocyte and T cells. Tim-3 mRNA expression in CD4+ and CD8+ cells was upregulated during disease progression of BLV infection. Interestingly, expression levels for Tim-3 and Gal-9 correlated positively with viral load in infected cattle. Furthermore, Tim-3 expression level closely correlated with up-regulation of IL-10 in infected cattle. The expression of IFN-γ and IL-2 mRNA was upregulated when PBMC from BLV-infected cattle were cultured with Cos-7 cells expressing Tim-3 to inhibit the Tim-3/Gal-9 pathway. Moreover, combined blockade of the Tim-3/Gal-9 and PD-1/PD-L1 pathways significantly promoted IFN-γ mRNA expression compared with blockade of the PD-1/PD-L1 pathway alone. These results suggest that Tim-3 is involved in the suppression of T cell function during BLV infection.

  15. [Novelties in the diagnostics and therapy of hairy cell leukemia].

    Science.gov (United States)

    Sári, Eszter; Rajnai, Hajnalka; Dénes, Kitti; Bödör, Csaba; Csomor, Judit; Körösmezey, Gábor; Tárkányi, Ilona; Eid, Hanna; Nagy, Zsolt; Demeter, Judit

    2016-06-01

    Differential diagnosis of hairy cell leukemia (HCL) and related disorders (hairy cell leukemia variant and splenic marginal zone lymphoma) is of utmost importance since the treatment and prognosis of these lymphomas differ. Since 2011 diagnosis of hairy cell leukemia has been easier because of discovery of the disease defining somatic mutation BRAF V600E mutation, which has been also known as driver mutation in malignant melanoma. The presence of this mutation enabled targeted molecular therapy in HCL as well. As first line therapy purine nucleoside analogues are the gold standard, but refractory/relapsed patient are candidates for targeted BRAF-inhibitor therapy. This manuscript serves as guidance in making diagnosis and standard treatment of HCL, and summarizes newest data about molecular therapy, including our single center experience collected from 75 patients. PMID:27275640

  16. Detection of bovine leukemia virus in cattle by the polymerase chain reaction.

    Science.gov (United States)

    Murtaugh, M P; Lin, G F; Haggard, D L; Weber, A F; Meiske, J C

    1991-06-01

    Bovine leukemia virus (BLV) is widely distributed in U.S. cattle herds. It infects B lymphocytes and causes neoplastic disease in 5-10% of infected animals. Direct economic losses are incurred as a result of death, reduced milk production and condemnation at slaughter. Thus the identification of cattle infected with BLV is of significant concern to the U.S. cattle industry. For this reason, polymerase chain reaction (PCR) amplification was used to examine seropositive and seronegative cattle for the presence of BLV DNA in peripheral blood mononuclear cells. Using an amplification protocol able to detect 1 viral genome in 100,000 cells, BLV was not detected in 7 seronegative cattle in an infected herd. BLV sequences were detected in 13 of 18 seropositive animals with various levels of infection as determined by in vitro lymphocyte culture and electron microscopy. An active infection was demonstrated in one animal, based on the presence of viral RNA. These findings indicate that PCR is a sensitive method for the detection of BLV in cattle and provides new information regarding the dynamics of the infection. PMID:1658030

  17. Seroepidemiological Survey of Infection by Feline Leukemia Virus and Immunodeficiency Virus in Madrid and Correlation with Some Clinical Aspects

    OpenAIRE

    Arjona, Alvaro; Escolar, Elena; Soto, Iria; Barquero, Nuria; Martin, Daniel; Gomez-Lucia, Esperanza

    2000-01-01

    A study of 180 healthy cats found that 15.6% were feline leukemia virus (FeLV) positive, 8.3% were feline immunodeficiency virus (FIV) positive, and 1.1% were FIV and FeLV positive, which corresponded to 30.4, 13.8, and 2.6, of 115 cats with FIV- and FeLV-related symptoms, respectively. Differences were seen in the sexes and ages of the populations studied. Anemia, leukopenia, and lymphopenia were the most frequent hematological abnormalities in infected cats.

  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. Mutated primer binding sites interacting with different tRNAs allow efficient murine leukemia virus replication

    DEFF Research Database (Denmark)

    Lund, Anders Henrik; Duch, M; Lovmand, J;

    1993-01-01

    Two Akv murine leukemia virus-based retroviral vectors with primer binding sites matching tRNA(Gln-1) and tRNA(Lys-3) were constructed. The transduction efficiency of these mutated vectors was found to be comparable to that of a vector carrying the wild-type primer binding site matching t......RNA(Pro). Polymerase chain reaction amplification and sequence analysis of transduced proviruses confirmed the transfer of vectors with mutated primer binding sites and further showed that tRNA(Gln-2) may act efficiently in conjunction with the tRNA(Gln-1) primer binding site. We conclude that murine leukemia virus...... can replicate by using various tRNA molecules as primers and propose primer binding site-tRNA primer interactions to be of major importance for tRNA primer selection. However, efficient primer selection does not require perfect Watson-Crick base pairing at all 18 positions of the primer binding site....

  20. Identification and targeting leukemia stem cells: The path to the cure for acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    Jianbiao; Zhou; Wee-Joo; Chng

    2014-01-01

    Accumulating evidence support the notion that acute myeloid leukemia(AML) is organized in a hierarchical system, originating from a special proportion of leukemia stem cells(LSC). Similar to their normal counterpart, hematopoietic stem cells(HSC), LSC possess selfrenewal capacity and are responsible for the continued growth and proliferation of the bulk of leukemia cells in the blood and bone marrow. It is believed that LSC are also the root cause for the treatment failure and relapse of AML because LSC are often resistant to chemotherapy. In the past decade, we have made significant advancement in identification and understanding the molecular biology of LSC, but it remains a daunting task to specifically targeting LSC, while sparing normalHSC. In this review, we will first provide a historical overview of the discovery of LSC, followed by a summary of identification and separation of LSC by either cell surface markers or functional assays. Next, the review will focus on the current, various strategies for eradicating LSC. Finally, we will highlight future directions and challenges ahead of our ultimate goal for the cure of AML by targeting LSC.

  1. Cordycepin Regulates GSK-3β/β-Catenin Signaling in Human Leukemia Cells

    OpenAIRE

    Ko, Bor-Sheng; Lu, Yi-Jhu; Yao, Wen-Ling; Liu, Tzu-An; Tzean, Shean-Shong; Shen, Tang-Long; Liou, Jun-Yang

    2013-01-01

    Background Leukemia stem cells (LSCs) are a limitless cell source for the initiation and maintenance of leukemia. Activation of the Wnt/β-catenin pathway is required for the survival and development of LSCs. Therefore, targeting β-catenin is considered a therapeutic strategy for the treatment of leukemia. The goal of this study was to explore whether cordycepin, an active component of the traditional medicine Cordyceps sinensis, regulates β-catenin expression in leukemia cells. Methodology an...

  2. Sequencing and phylogenetic analysis of the gp51 gene from Korean bovine leukemia virus isolates

    OpenAIRE

    Lee, Eunjung; Kim, Eun-Ju; Joung, Ha-Kyung; Kim, Bo-hye; SONG, Jae-Young; Cho, In-Soo; Lee, Kyoung-Ki; Shin, Yeun-Kyung

    2015-01-01

    Background Bovine Leukemia virus (BLV) infection of cattle has been reported in Korea for more than three decades. However, to date, there have been few studies regarding Korean BLV since 1980s. Thus, the purpose of this study is to perform a diagnosis and molecular characterization of BLV strains circulating in Korea and to estimate genetic diversity of different genotypes of BLV. Method To investigate the distribution of BLV variants in the world and assess the evolutionary history of Korea...

  3. Bovine Leukemia Virus Small Noncoding RNAs Are Functional Elements That Regulate Replication and Contribute to Oncogenesis In Vivo

    Science.gov (United States)

    Hamaidia, Malik; de Brogniez, Alix; Gutiérrez, Gerónimo; Renotte, Nathalie; Reichert, Michal; Trono, Karina; Willems, Luc

    2016-01-01

    Retroviruses are not expected to encode miRNAs because of the potential problem of self-cleavage of their genomic RNAs. This assumption has recently been challenged by experiments showing that bovine leukemia virus (BLV) encodes miRNAs from intragenomic Pol III promoters. The BLV miRNAs are abundantly expressed in B-cell tumors in the absence of significant levels of genomic and subgenomic viral RNAs. Using deep RNA sequencing and functional reporter assays, we show that miRNAs mediate the expression of genes involved in cell signaling, cancer and immunity. We further demonstrate that BLV miRNAs are essential to induce B-cell tumors in an experimental model and to promote efficient viral replication in the natural host. PMID:27123579

  4. Pathogenicity Induced by Feline Leukemia Virus, Rickard Strain, Subgroup A Plasmid DNA (pFRA)

    OpenAIRE

    Chen, Hang; Bechtel, Marta K.; Shi, Yan; Phipps, Andrew; Mathes, Lawrence E.; Hayes, Kathleen A.; Roy-Burman, Pradip

    1998-01-01

    A new provirus clone of feline leukemia virus (FeLV), which we named FeLV-A (Rickard) or FRA, was characterized with respect to viral interference group, host range, complete genome sequence, and in vivo pathogenicity in specific-pathogen-free newborn cats. The in vitro studies indicated the virus to be an ecotropic subgroup A FeLV with 98% nucleotide sequence homology to another FeLV-A clone (F6A/61E), which had also been fully sequenced previously. Since subgroup B polytropic FeLVs (FeLV-B)...

  5. Serological and molecular detection of bovine leukemia virus in cattle in Iraq.

    Science.gov (United States)

    Khudhair, Yahia Ismail; Hasso, Saleem Amin; Yaseen, Nahi Y; Al-Shammari, Ahmed Majeed

    2016-01-01

    Bovine leukemia virus (BLV) is highly endemic in many countries, including Iraq, and it impacts the beef and dairy industries. The current study sought to determine the percentage of BLV infection and persistent lymphocytosis (PL) in cattle in central Iraq. Hematological, serological, and molecular observations in cross breeds and local breeds of Iraqi cattle naturally infected with BLV were conducted in the peripheral blood mononuclear cells of 400 cattle (340 cross breed and 60 local breed) using enzyme-linked immunosorbent assay and polymerase chain reaction (PCR). On the basis of the absolute number of lymphocytes, five of the 31 positive PCR cases had PL. Among these leukemic cattle, one case exhibited overt neutrophilia. Serum samples were used to detect BLV antibodies, which were observed in 28 (7%) samples. PCR detected BLV provirus in 31 samples (7.75%). All 28 of the seropositive samples and the 3 seronegative samples were positive using PCR. Associations were observed between bovine leukosis and cattle breed, age and sex. Age-specific analysis showed that the BLV percentage increased with age in both breeds. Female cattle (29 animals; 7.34%) exhibited significantly higher infectivity than male cattle (two animals; 4.34%). In conclusion, comprehensive screening for all affected animals is needed in Iraq; programs that segregate cattle can be an effective and important method to control and/or eliminate the BLV. PMID:27273225

  6. Interaction between Bovine leukemia virus (BLV) infection and age on telomerase misregulation.

    Science.gov (United States)

    Hemmatzadeh, Farhid; Keyvanfar, Hadi; Hasan, Noor Haliza; Niap, Faustina; Bani Hassan, Ebrahim; Hematzade, Azar; Ebrahimie, Esmaeil; McWhorter, Andrea; Ignjatovic, Jagoda

    2015-06-01

    Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis (EBL). BLV can interact with telomerase and inhibits telomere shortening, contributing in leukemogenesis and tumour induction. The role of telomerase in BLV-induced lymphosarcoma and aging has been extensively studied. To date, the interaction of both BLV and aging on telomerase mis-regulation have, however, not been investigated. In the present study, telomerase activity in BLV positive and negative cows was compared over a wide range of ages (11-85 months). Lymphocyte counts were also measured in both BLV positive and negative groups. Telomerase activity was detected in all BLV infected animals with persistent lymphocytosis (PL), especially in older individuals. This study revealed that the cells undergo the natural telomerase shortening even in the presence of an existing viral infection. We also show that viral infection, especially during the PL phase of the disease, increases telomerase activity. A statistically significant interaction between age and viral infection was observed for telomere shortening during BLV infection. Older animals with BLV infection, especially those with persistent lymphocytosis or visible tumors, exhibited a sharp increase in telomerase activity. This study demonstrates that there is a significant interaction between BLV infection and telomerase up-regulation and lymphocytosis. PMID:25665900

  7. Functional dissection of the Moloney murine leukemia virus envelope protein gp70.

    Science.gov (United States)

    Bae, Y; Kingsman, S M; Kingsman, A J

    1997-03-01

    The envelope protein of Moloney murine leukemia virus (Mo-MLV) is a complex glycoprotein that mediates receptor binding and entry via fusion with cell membranes. By using a series of substitution mutations and truncations in the Mo-MLV external envelope surface protein gp70, we have identified regions important for these processes. Firstly, truncations of gp70 revealed that the minimal continuous receptor-binding region is amino acids 9 to 230, in broad agreement with other studies. Secondly, within this region there are two key basic amino acids, Arg-83 and Arg-95, that are essential for receptor binding and may interact with a negatively charged residue(s) or with the pi electrons of the aromatic ring on a hydrophobic residue(s) in the basic amino acid transporter protein that is the Mo-MLV ecotropic receptor. Finally, we showed that outside the minimal receptor-binding region at amino acids 2 to 8, there is a region that is essential for postbinding fusion events. PMID:9032341

  8. Association of feline leukemia virus with lymphosarcoma and other disorders in the cat.

    Science.gov (United States)

    Cotter, S M; Hardy, W D; Essex, M

    1975-03-01

    Two hundred fifty Boston cats with disorders such as lymphosarcoma, myeloproliferative disease, anemia, glomerulonephritis, pregnancy abnormalities, feline infectious peritonitis, toxoplasmosis, and various bacterial infections were examined for feline leukemia virus (FeLV) by immunofluorescence. Antibody titers against feline oncornavirus-associated cell membrane antigen (FOCMA) were tested in 133 of these cats. The tests for FeLV and FOCMA antibody were also conducted among healthy cats not known to have been exposed to FeLV, as well as among healthy cats from households where FeLV was known to be present. Most of the cats with lymphosarcoma and the other aforementioned disorders were infected with FeLV and low FOCMA antibody titers. Healthy cats known to have been exposed to FeLV were often viremic, but those that remained healthy were able to develop high FOCMA antibody titers. Healthy cats without known prior exposure to FeLV were unlikely to be viremic but often had detectable FOCMA antibody titers, indicating that some exposure occurs under natural conditions in the Boston area. The association of FeLV with infections other than lymphosarcoma was assumed to be caused by the immunosuppresive effect of FeLV, thus allowing development of disease. PMID:163223

  9. Advanced Data Mining of Leukemia Cells Micro-Arrays

    Directory of Open Access Journals (Sweden)

    Ryan M. Pierce

    2009-12-01

    Full Text Available This paper provides continuation and extensions of previous research by Segall and Pierce (2009a that discussed data mining for micro-array databases of Leukemia cells for primarily self-organized maps (SOM. As Segall and Pierce (2009a and Segall and Pierce (2009b the results of applying data mining are shown and discussed for the data categories of microarray databases of HL60, Jurkat, NB4 and U937 Leukemia cells that are also described in this article. First, a background section is provided on the work of others pertaining to the applications of data mining to micro-array databases of Leukemia cells and micro-array databases in general. As noted in predecessor article by Segall and Pierce (2009a, micro-array databases are one of the most popular functional genomics tools in use today. This research in this paper is intended to use advanced data mining technologies for better interpretations and knowledge discovery as generated by the patterns of gene expressions of HL60, Jurkat, NB4 and U937 Leukemia cells. The advanced data mining performed entailed using other data mining tools such as cubic clustering criterion, variable importance rankings, decision trees, and more detailed examinations of data mining statistics and study of other self-organized maps (SOM clustering regions of workspace as generated by SAS Enterprise Miner version 4. Conclusions and future directions of the research are also presented.

  10. IFN-γ promotes graft-versus-leukemia effects without directly interacting with leukemia cells in mice after allogeneic hematopoietic cell transplantation

    OpenAIRE

    Yang, Yanping; Wang, Hui; Yu, Hui; Yeap, Beow Yong; Liang, Tingting; Wang, Guanjun; Cheng, Tao; Yang, Yong-Guang

    2011-01-01

    The ability of IFN-γ to enhance graft-versus-leukemia (GVL) activity without direct interaction with leukemia cells was examined by comparing GVL effects against IFN-γ receptor-deficient (GRKO) leukemia between wild-type (WT) and IFN-γ–deficient (GKO) allogeneic hematopoietic cell transplantation (allo-HCT). We established a primary IFN-γ–unresponsive T-cell leukemia model using virally-transduced GRKO B6 mouse bone marrow cells overexpressing Notch1. We first assessed GVL effects in lethally...

  11. NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells

    NARCIS (Netherlands)

    S.W. Paugh (Steven); E.J. Bonten (Erik J.); D. Savic (Daniel); L.B. Ramsey (Laura B.); W.E. Thierfelder (William E.); P. Gurung (Prajwal); R.K.S. Malireddi (R. K. Subbarao); M. Actis (Marcelo); A. Mayasundari (Anand); J. Min (Jaeki); D.R. Coss (David R.); L.T. Laudermilk (Lucas T.); J.C. Panetta (John); J.R. McCorkle (J. Robert); Y. Fan (Yiping); K.R. Crews (Kristine R.); G. Stocco (Gabriele); M.R. Wilkinson (Mark R.); A.M. Ferreira (Antonio M.); C. Cheng (Cheng); W. Yang (Wenjian); S.E. Karol (Seth E.); C.A. Fernandez (Christian A.); B. Diouf (Barthelemy); C. Smith (Colton); J.K. Hicks (J Kevin); A. Zanut (Alessandra); A. Giordanengo (Audrey); D.J. Crona; J.J. Bianchi (Joy J.); L. Holmfeldt (Linda); C.G. Mullighan (Charles); M.L. den Boer (Monique); R. Pieters (Rob); S. Jeha (Sima); T.L. Dunwell (Thomas L.); F. Latif (Farida); D. Bhojwani (Deepa); W.L. Carroll (William L.); C.-H. Pui (Ching-Hon); R.M. Myers (Richard M.); R.K. Guy (R Kiplin); T.-D. Kanneganti (Thirumala-Devi); M.V. Relling (Mary); W.E. Evans (William)

    2015-01-01

    textabstractGlucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and resistance to glucocorticoids in leukemia cells confers poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the prednisolone sensitivity of primary leukemia ce

  12. Childhood Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. It is the most common type of childhood cancer. ... blood cells help your body fight infection. In leukemia, the bone marrow produces abnormal white blood cells. ...

  13. Serological analysis of cell surface antigens of null cell acute lymphocytic leukemia by mouse monoclonal antibodies.

    OpenAIRE

    Ueda, R; Tanimoto, M; Takahashi, T.; Ogata, S; Nishida, K; Namikawa, R.; Nishizuka, Y; Ota, K.

    1982-01-01

    Nine antigens systems were defined. Two were related to HLA-A,B,C and to Ia-like antigens; the others could be grouped into three categories. (i) NL-22, NL-1: NL-22 antibody reacted with leukemia cells from 12 to 16 cases of null cell acute lymphocytic leukemia (null-ALL) but not with any other type of leukemia tested or with lymphoid cells of various origins. Among cultured cell lines tested, one (NALM-6) of three null-ALL cell lines was positive, the others were negative. Absorption analysi...

  14. Serological survey of Toxoplasma gondii, Dirofilaria immitis, Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) infections in pet cats in Bangkok and vicinities, Thailand

    Science.gov (United States)

    The seroprevalence of Toxoplasma gondii, Dirofilaria immitis (heartworm), feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) infections was examined using serum or plasma samples from 746 pet cats collected between May and July 2009 from clinics and hospitals located in and around ...

  15. Seroprevalence of antibodies against bovine leukemia virus, bovine viral diarrhea virus, Mycobacterium avium subspecies paratuberculosis, and Neospora caninum in dairy cattle in Saskatchewan

    OpenAIRE

    Vanleeuwen, John A.; Forsythe, LeeAnn; Tiwari, Ashwani; Chartier, Renee

    2005-01-01

    Blood was drawn from 1530 dairy cows in 51 herds. For antibodies against bovine leukemia virus, Mycobacterium avium subspecies paratuberculosis, and Neospora caninum, 37.4%, 2.7%, and 5.6% of cows were test positive, respectively, while 29.2% of herds had unvaccinated animals with ≥ 1:64 for bovine viral diarrhea virus.

  16. Increased risk for lymphoma and glomerulonephritis in a closed population of cats exposed to feline leukemia virus.

    Science.gov (United States)

    Francis, D P; Essex, M; Jakowski, R M; Cotter, S M; Lerer, T J; Hardy, W D

    1980-03-01

    Feline leukemia virus (FeLV)-associated diseases were observed in a household in eastern Connecticut having 134 cats over a period of five and a half years. FeLV-positive cats had a much higher mortality rate (34.6 deaths per 1000 cat-months of follow-up) than did FeLV-negative cats (8.9 deaths per 1000 cat-months of follow-up). The leading cause of death was glomerulonephritis followed by lymphoma. The relative risk for virus-positive cats as compared to virus-negative cats for the two diseases was 9.9 and 9.6, respectively. The major risk factors for the development of lymphoma were virus positivity and low antibody titer to the feline oncornavirus-associated cell membrane antigen (FOCMA). No significant differences in cancer incidence were seen between the two major breeds (Abyssinian and Burmese) in the household. An older age at arrival in the house decreased death rates for all causes in the household, but it did not significantly affect death rates from lymphoma, although there was a positive trend. PMID:6244730

  17. Hemotopoetic radiation damage in mice with the leukemia virus

    International Nuclear Information System (INIS)

    Effect of congenital carriage of tumorgenic viruses on the radioresistance of mice exposed to ionizing radiation is studied. Mice were irradiated by γ-rays of 137Cs source at 0.5-8.0 Gy doses and 1.5 Gy/min dose rate. It is shown that mice-carriers of virus (T-leukosis) are more radiosensitive according to survival rate and hemopoiesis state. It is supposed that the decrease in leukosal mice ability to repair postradiation damages is the basis of these regularities

  18. Oncogenic Kras initiates leukemia in hematopoietic stem cells.

    OpenAIRE

    Amit J Sabnis; Cheung, Laurene S.; Monique Dail; Hio Chung Kang; Marianne Santaguida; Hermiston, Michelle L.; Emmanuelle Passegué; Kevin Shannon; Braun, Benjamin S.

    2009-01-01

    Author Summary Ras proteins act as molecular switches that relay growth signals from outside the cell. This mechanism is often subverted in cancer, and Ras proteins are activated directly by RAS gene mutations in approximately one-third of human malignancies. We have modeled this in mice engineered to have a Ras mutation. These mice develop a disease similar to chronic leukemias in humans called myeloproliferative disorders. It is marked by a fatal accumulation of mature and immature cells in...

  19. Oncogenic Kras Initiates Leukemia in Hematopoietic Stem Cells

    OpenAIRE

    Sabnis, Amit J; Cheung, Laurene S.; Dail, Monique; Kang, Hio Chung; Santaguida, Marianne; Hermiston, Michelle L.; Passegué, Emmanuelle; Shannon, Kevin; Braun, Benjamin S.

    2009-01-01

    Author Summary Ras proteins act as molecular switches that relay growth signals from outside the cell. This mechanism is often subverted in cancer, and Ras proteins are activated directly by RAS gene mutations in approximately one-third of human malignancies. We have modeled this in mice engineered to have a Ras mutation. These mice develop a disease similar to chronic leukemias in humans called myeloproliferative disorders. It is marked by a fatal accumulation of mature and immature cells in...

  20. Mantle cell leukemia as a cause of leukostasis

    Directory of Open Access Journals (Sweden)

    Rappaport E

    2011-04-01

    Full Text Available Daniel Smith1, Christian Cable2, Cary Chisholm1, Walter Linz1, William Koss1, Sheila Dobin1, Edward Rappaport11Department of Pathology, 2Internal Medicine, Scott and White Healthcare/Texas A & M Health Science Center College of Medicine, Temple, TX, USAAbstract: A 72-year-old man was admitted with hypoxemic respiratory distress. Given a white blood cell count of 600 × 109/L and symptoms of leukostasis, emergency leukapheresis was initiated. The white blood cell count immediately after the first leukapheresis was paradoxically increased to over 700 × 109/L. Peripheral blood smear findings showed morphologically immature mononuclear cells and numerous circulating mitotic figures. Initial flow cytometry results showed a lambda light chain-restricted B lymphoid population positive for CD20, CD19, CD5, and FMC-7, and negative for TdT, CD10, CD23, CD34, CD117, and myeloid markers, suggesting classification as a blastoid variant of mantle cell lymphoma in a leukemic phase. Subsequent testing using DNA fluorescence in situ hybridization was positive for t(11;14, confirming the diagnosis of mantle cell leukemia. Although mantle cell lymphoma occasionally transforms or can even present as leukemia (leukocytes >40 × 109/L, it is rare for it to present with such profound leukocytosis and an overwhelming number of pleomorphic/blastoid forms. Although morphology suggested acute lymphoblastic leukemia, a more specific diagnosis of blastoid variant mantle cell lymphoma was obtained in 12 hours by applying complementary techniques of flow cytometry and rapid cytogenetics.Keywords: mantle cell lymphoma, chemotherapy, leukapheresis, lymphocytic leukemia

  1. Short communication: Relationship between the level of bovine leukemia virus antibody and provirus in blood and milk of cows from a naturally infected herd.

    Science.gov (United States)

    Jaworski, Juan P; Porta, Natalia G; Gutierrez, Geronimo; Politzki, Romina P; Álvarez, Irene; Galarza, Roxana; Abdala, Alejandro; Calvinho, Luis; Trono, Karina G

    2016-07-01

    We explored the relationship between the level of bovine leukemia virus antibodies and provirus load during natural infection. For that purpose, a set of 50 blood and milk paired samples were analyzed for the presence of bovine leukemia virus provirus and antibodies. Additionally, provirus load and antibody titers were measured and the relationship between these variables was investigated. Bovine leukemia provirus was detected in 59% of milk samples and a negative correlation was observed between the level of milk provirus load and milk antibody titers. By the consumption of raw milk, calves might be exposed to bovine leukemia virus favoring the perinatal transmission of this disease. PMID:27132093

  2. Role for elevated H-2 antigen expression in resistance to neoplasia caused by radiation-induced leukemia virus. Enhancement of effective tumor surveillance by killer lymphocytes

    International Nuclear Information System (INIS)

    Resistance to neoplasia caused by radiation-induced leukemia virus (RadLV) is mediated by gene(s) in the H-2D region of the major histocompatibility complex. The previous observation that rapid increases in cellular synthesis and cell-surface expression of H-2 antigens are detectable immediately after virus inoculation has suggested that altered expression of H-2 antigens may play a significant role in the mechanism(s) of host defense to virus infection. This concept is supported by the following observations. First, cell-mediated immunity against RadLV transformed or infected cells can be detected with ease when H-2-positive target cells are used in the cell-mediated lympholysis (CML) assay. Second, resistant mice develop greater numbers of effectors when infected with RadLV than do susceptible mice. Third, injection of normal (uninfected) thymocytes into syngeneic recipients of resistant or susceptible H-2 type does not stimulate a CML response. However, injection of RadLV infected thymocytes from resistant mice produces a vigorous CMI response, and such thymocytes elicit the strongest response at a time when both H-2 and viral antigen expression is elevated. By contrast, injection of infected thymocytes from susceptible mice, which express viral antigens, but low levels of H-2 antigens, does not stimulate a CML reaction. These findings may explain the easier induction of leukemia found by many investigators when virus is inoculated into neonatal mice and the preferential thymus tropism of some oncogenic type-C RNA virus. Cells expressing very low levels of H-2, such as thymocytes, may serve as permissive targets for virus infection because they lack an important component (H-2 antigens) of the dual or altered recognition signal required to trigger a defensive host immune response

  3. Splicing of Friend Murine Leukemia Virus env-mRNA Enhances Its Ability to Form Polysomes.

    Science.gov (United States)

    Machinaga, Akihito; Ishihara, Syuhei; Shirai, Akiko; Takase-Yoden, Sayaka

    2016-01-01

    Friend murine leukemia virus (MLV) belongs to the gamma retroviruses of the Retroviridae family. The positive-sense RNA of its genome contains a 5' long terminal repeat (LTR), 5' leader sequence, gag, pol, env, and 3' LTR. Transcription from proviral DNA begins from the R region of the 5' LTR and ends at the polyadenylation signal located at the R region of the other end of the 3' LTR. There is a 5' splice site in the 5' leader sequence and a 3' splice site at the 3' end of the pol region. Both full-length unspliced mRNAs and a singly spliced mRNA (env-mRNA) are produced in MLV-infected cells. The MLV Env protein plays important roles both in viral adsorption to host cells and in neuropathogenic disease in MLV-infected mice and rats. Understanding the regulatory mechanisms controlling Env expression is important for determining the functions of the Env protein. We have previously shown that splicing increases env-mRNA stability and translation efficiency. Generally, mRNA polysome formation correlates with translation efficiency. Therefore, here we investigated the effects of env-mRNA splicing on polysome formation to identify mechanisms for Env up-regulation due to splicing. We performed polysome profile analyses using Env-expression plasmids producing spliced or unspliced env-mRNA and showed that the former formed polysomes more efficiently than the latter. Thus, splicing of env-mRNA facilitated polysome formation, suggesting that this contributes to up-regulation of Env expression. We replaced the env region of the expression plasmids with a luciferase (luc) gene, and found that in this case both unspliced and spliced luc-mRNA formed polysomes to a similar extent. Thus, we conclude that whether mRNA polysome formation is affected by splicing depends on the structure of gene in question. PMID:26909075

  4. Detection and molecular characterization of bovine leukemia virus in Philippine cattle.

    Science.gov (United States)

    Polat, Meripet; Ohno, Ayumu; Takeshima, Shin-Nosuke; Kim, Jiyun; Kikuya, Mari; Matsumoto, Yuki; Mingala, Claro Niegos; Onuma, Misao; Aida, Yoko

    2015-01-01

    Bovine leukemia virus (BLV) is the etiological agent of enzootic bovine leukosis, which is the most common neoplastic disease of cattle. BLV infects cattle worldwide, imposing a severe economic impact on the dairy cattle industry. However, there are no comprehensive studies on the distribution of BLV in the Philippines, and the genetic characteristics of Philippine BLV strains are unknown. Therefore, the aim of this study was to detect BLV infections in the Philippines and determined their genetic variability. Blood samples were obtained from 1116 cattle from different farms on five Philippine islands, and BLV provirus was detected by BLV-CoCoMo-qPCR-2 and nested PCR targeting BLV long terminal repeats. Out of 1116 samples, 108 (9.7 %) and 54 (4.8 %) were positive for BLV provirus, as determined by BLV-CoCoMo-qPCR-2 and nested PCR, respectively. Of the five islands, Luzon Island showed the highest prevalence of BLV infection (23.1 %). Partial env gp51 genes from 43 samples, which were positive for BLV provirus by both methods, were sequenced for phylogenetic analysis. Phylogenetic analysis based on a 423-bp fragment of the env gene revealed that Philippine BLV strains clustered into either genotype 1 or genotype 6. Substitutions were mainly found in antigenic determinants, such as the CD4(+) T-cell epitope, the CD8(+) T-cell epitope, the second neutralizing domain, B and E epitopes, and these substitutions varied according to genotype. This study provides comprehensive information regarding BLV infection levels in the Philippines and documents the presence of two BLV genotypes, genotypes 1 and 6, in this population. PMID:25399399

  5. Preventive and therapeutic strategies for bovine leukemia virus: lessons for HTLV.

    Science.gov (United States)

    Rodríguez, Sabrina M; Florins, Arnaud; Gillet, Nicolas; de Brogniez, Alix; Sánchez-Alcaraz, María Teresa; Boxus, Mathieu; Boulanger, Fanny; Gutiérrez, Gerónimo; Trono, Karina; Alvarez, Irene; Vagnoni, Lucas; Willems, Luc

    2011-07-01

    Bovine leukemia virus (BLV) is a retrovirus closely related to the human T-lymphotropic virus type 1 (HTLV-1). BLV is a major animal health problem worldwide causing important economic losses. A series of attempts were developed to reduce prevalence, chiefly by eradication of infected cattle, segregation of BLV-free animals and vaccination. Although having been instrumental in regions such as the EU, these strategies were unsuccessful elsewhere mainly due to economic costs, management restrictions and lack of an efficient vaccine. This review, which summarizes the different attempts previously developed to decrease seroprevalence of BLV, may be informative for management of HTLV-1 infection. We also propose a new approach based on competitive infection with virus deletants aiming at reducing proviral loads. PMID:21994777

  6. Preventive and Therapeutic Strategies for Bovine Leukemia Virus: Lessons for HTLV

    Directory of Open Access Journals (Sweden)

    Lucas Vagnoni

    2011-07-01

    Full Text Available Bovine leukemia virus (BLV is a retrovirus closely related to the human T-lymphotropic virus type 1 (HTLV-1. BLV is a major animal health problem worldwide causing important economic losses. A series of attempts were developed to reduce prevalence, chiefly by eradication of infected cattle, segregation of BLV-free animals and vaccination. Although having been instrumental in regions such as the EU, these strategies were unsuccessful elsewhere mainly due to economic costs, management restrictions and lack of an efficient vaccine. This review, which summarizes the different attempts previously developed to decrease seroprevalence of BLV, may be informative for management of HTLV-1 infection. We also propose a new approach based on competitive infection with virus deletants aiming at reducing proviral loads.

  7. Preventive and Therapeutic Strategies for Bovine Leukemia Virus: Lessons for HTLV

    Science.gov (United States)

    Rodríguez, Sabrina M.; Florins, Arnaud; Gillet, Nicolas; de Brogniez, Alix; Sánchez-Alcaraz, María Teresa; Boxus, Mathieu; Boulanger, Fanny; Gutiérrez, Gerónimo; Trono, Karina; Alvarez, Irene; Vagnoni, Lucas; Willems, Luc

    2011-01-01

    Bovine leukemia virus (BLV) is a retrovirus closely related to the human T-lymphotropic virus type 1 (HTLV-1). BLV is a major animal health problem worldwide causing important economic losses. A series of attempts were developed to reduce prevalence, chiefly by eradication of infected cattle, segregation of BLV-free animals and vaccination. Although having been instrumental in regions such as the EU, these strategies were unsuccessful elsewhere mainly due to economic costs, management restrictions and lack of an efficient vaccine. This review, which summarizes the different attempts previously developed to decrease seroprevalence of BLV, may be informative for management of HTLV-1 infection. We also propose a new approach based on competitive infection with virus deletants aiming at reducing proviral loads. PMID:21994777

  8. Cannabinoids induce incomplete maturation of cultured human leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Murison, G.; Chubb, C.B.H.; Maeda, S.; Gemmell, M.A.; Huberman, E.

    1987-08-01

    Monocyte maturation markers were induced in cultured human myeloblastic ML-2 leukemia cells after treatment for 1-6 days with 0.03-30 ..mu..M ..delta../sup 9/-tetrahydrocannabinol (THC), the major psychoactive component of marijuana. After a 2-day or longer treatment, 2- to 5-fold increases were found in the percentages of cells exhibiting reactivity with either the murine OKM1 monoclonal antibody of the Leu-M5 monoclonal antibody, staining positively for nonspecific esterase activity, and displaying a promonocyte morphology. The increases in these differentiation markers after treatment with 0.03-1 ..mu..M THC were dose dependent. At this dose range, THC did not cause an inhibition of cell growth. The THC-induced cell maturation was also characterized by specific changes in the patterns of newly synthesized proteins. The THC-induced differentiation did not, however, result in cells with a highly developed mature monocyte phenotype. However, treatment of these incompletely matured cells with either phorbol 12-myristate 13-acetate of 1..cap alpha..,25-dihydroxycholecalciferol, which are inducers of differentiation in myeloid leukemia cells (including ML-2 cells), produced cells with a mature monocyte morphology. The ML-2 cell system described here may be a useful tool for deciphering critical biochemical events that lead to the cannabinoid-induced incomplete cell differentiation of ML-2 cells and other related cell types. Findings obtained from this system may have important implications for studies of cannabinoid effects on normal human bone-marrow progenitor cells.

  9. 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

  10. Altered plasma concentrations of sex hormones in cats infected by feline immunodeficiency virus or feline leukemia virus.

    Science.gov (United States)

    Tejerizo, G; Doménech, A; Illera, J-C; Silván, G; Gómez-Lucía, E

    2012-02-01

    Gender differences may affect human immunodeficiency virus (HIV) infection in humans and may be related to fluctuations in sex hormone concentration. The different percentage of male and female cats observed to be infected by feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) has been traditionally explained through the transmission mechanisms of both viruses. However, sexual hormones may also play a role in this different distribution. To study this possibility, 17β-estradiol, progesterone, testosterone, and dehydroepiandrosterone (DHEA) concentrations were analyzed using a competitive enzyme immunoassay in the plasma of 258 cats naturally infected by FIV (FIV(+)), FeLV (FeLV(+)), or FeLV and FIV (F(-)F(+)) or negative for both viruses, including both sick and clinically healthy animals. Results indicated that the concentrations of 17β-estradiol and testosterone were significantly higher in animals infected with FIV or FeLV (P FIV(+) females had higher DHEA concentrations than the corresponding males (P FIV and FeLV infections are associated with an important deregulation of steroids, possibly from early in the infection process, which might have decisive consequences for disease progression. PMID:22177694

  11. Targeting Leukemia Stem Cells in vivo with AntagomiR-126 Nanoparticles in Acute Myeloid Leukemia

    Science.gov (United States)

    Dorrance, Adrienne M.; Neviani, Paolo; Ferenchak, Greg J.; Huang, Xiaomeng; Nicolet, Deedra; Maharry, Kati S.; Ozer, Hatice G; Hoellarbauer, Pia; Khalife, Jihane; Hill, Emily B.; Yadav, Marshleen; Bolon, Brad N.; Lee, Robert J.; Lee, L.James; Croce, Carlo M.; Garzon, Ramiro; Caligiuri, Michael A.; Bloomfield, Clara D.; Marcucci., Guido

    2015-01-01

    Current treatments for acute myeloid leukemia (AML) are designed to target rapidly dividing blast populations with limited success in eradicating the functionally distinct leukemia stem cell (LSC) population, which is postulated to be responsible for disease resistance and relapse. We have previously reported high miR-126 expression levels to be associated with a LSC-gene expression profile. Therefore, we hypothesized that miR-126 contributes to “stemness” and is a viable target for eliminating the LSC in AML. Here we first validate the clinical relevance of miR-126 expression in AML by showing that higher expression of this microRNA (miR) is associated with worse outcome in a large cohort of older (≥60 years) cytogenetically normal AML patients treated with conventional chemotherapy. We then show that miR-126 overexpression characterizes AML LSC-enriched cell subpopulations and contributes to LSC long-term maintenance and self-renewal. Finally, we demonstrate the feasibility of therapeutic targeting of miR-126 in LSCs with novel targeting nanoparticles (NP) containing antagomiR-126 resulting in in vivo reduction of LSCs likely by depletion of the quiescent cell subpopulation. Our findings suggest that by targeting a single miR, i.e., miR-126, it is possible to interfere with LSC activity, thereby opening potentially novel therapeutic approaches to treat AML patients. PMID:26055302

  12. TRAIL-mediated killing of acute lymphoblastic leukemia by plasmacytoid dendritic cell-activated natural killer cells

    OpenAIRE

    Lelaidier, Martin; Dìaz-Rodriguez, Yildian; Cordeau, Martine; Cordeiro, Paulo; Haddad, Elie; Herblot, Sabine; Duval, Michel

    2015-01-01

    Acute lymphoblastic leukemia (ALL) still frequently recurs after hematopoietic stem cell transplantation (HSCT), underscoring the need to improve the graft-versus-leukemia (GvL) effect. Natural killer (NK) cells reconstitute in the first months following HSCT when leukemia burden is at its lowest, but ALL cells have been shown to be resistant to NK cell-mediated killing. We show here that this resistance is overcome by NK cell stimulation with TLR-9-activated plasmacytoid dendritic cells (pDC...

  13. Evidence of feline immunodeficiency virus, feline leukemia virus, and Toxoplasma gondii in feral cats on Mauna Kea, Hawaii

    Science.gov (United States)

    Danner, R.M.; Goltz, Dan M.; Hess, S.C.; Banko, P.C.

    2007-01-01

    We determined prevalence to feline immunodeficiency virus (FIV) antibodies, feline leukemia virus (FeLV) antigen, and Toxoplasma gondii antibodies in feral cats (Felis catus) on Mauna Kea Hawaii from April 2002 to May 2004. Six of 68 (8.8%) and 11 of 68 (16.2%) cats were antibody positive to FIV and antigen positive for FeLV, respectively; 25 of 67 (37.3%) cats were seropositive to T. gondii. Antibodies to FeLV and T. gondii occurred in all age and sex classes, but FIV occurred only in adult males. Evidence of current or previous infections with two of these infectious agents was detected in eight of 64 cats (12.5%). Despite exposure to these infectious agents, feral cats remain abundant throughout the Hawaiian Islands. ?? Wildlife Disease Association 2007.

  14. The "putative" leucine zipper region of murine leukemia virus transmembrane protein (P15e) is essential for viral infectivity.

    Science.gov (United States)

    Ramsdale, E E; Kingsman, S M; Kingsman, A J

    1996-06-01

    In order to determine the role of the putative leucine zipper region of murine leukemia virus (MLV) transmembrane protein p15E, nine mutations in this region were introduced by site-directed mutagenesis. None of these mutations affected the expression or transport of the envelope protein or incorporation into virions. The mutants were analyzed for their ability to infect NIH3T3 cells and to induce cell fusion in a rat XC cell fusion assay. Mutations removing the charge of the hydrophilic residues reduced infectivity in NIH3T3 cells but had either no effect or a minor effect on envelope-induced XC cell fusion. Six mutations of hydrophobic residues of the putative leucine zipper region were constructed; four completely abolished the ability to infect NIH3T3 cells and these mutant envelopes were also unable to induce cell fusion in the XC cell fusion assay. These data demonstrate the absolute requirement for the putative leucine zipper region for both fusion and infection of MLV. PMID:8659102

  15. Allogeneic stem cell transplantation in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Natasha Ali

    2012-11-01

    Full Text Available We report a case series of 12 patients with acute myeloid leukemia who underwent allogeneic stem cell transplant with a matched related donor. Male to female ratio was 1:1. The main complication post-transplant was graft-versus-host disease (n=7 patients. Transplant-related mortality involved one patient; cause of death was multi-organ failure. After a median follow up of 36.0±11.3 months, overall survival was 16%.

  16. RESULTS OF HEMATOPOIETIC CELL TRANSPLANTATION IN PEDIATRIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    A. Mousavi

    2008-05-01

    Full Text Available Hematopoietic cell transplantation (HCT is an accepted treatment for acute myeloid leukemia (AML in first remission, the treatment of choice for chronic myeloid leukemia (CML and high risk groups of ALL who relapse with conventional chemotherapy. We assessed results of HCT for pediatric leukemia in our center. A total of 92 children, 63 with diagnose of AML, 23 with ALL and 6 with CML received allogeneic transplantation from HLA full matched siblings (57.6% and autologous transplantation (42.4%. Source of hematopoietic cells were peripheral blood 83.7%, bone marrow 15.2% and cord blood 1.6%. The median transplanted nucleated cells were 6.4 ± 4.7 ×108 /Kg (body weight of patients and mononuclear cells were 5.5 ± 2.9×108/Kg. The most common conditioning regimens were cyclophosphamide + busulfan. Prophylaxis regimen for GVHD was cyclosporin ± methotrexate. GVHD occurred in 50 (54.3% patients. Eighty five of children had engraftment, 26 (28.6% relapsed and 57 (62% are alive. The most common cause of death was relapse (68.6%. Five years overall survival of patients with AML and ALL were 49% and 44% respectively and disease free survival of them were 52% and 49%. One year overall survival and disease free survival of CML was 57%. Overall survival increased with increasing age of patients at transplantation time (P = 0.06. Longer survival significantly related to earlier WBC and platelet recovery (P < 0.0001 and P = 0.006 respectively. Considering acceptable overall and disease free survival of patients after HCT, we concluded that is a good modality in treatment of leukemia of children.

  17. Long Terminal Repeat Regions from Exogenous but Not Endogenous Feline Leukemia Viruses Transactivate Cellular Gene Expression

    OpenAIRE

    Ghosh, Sajal K.; Roy-Burman, Pradip; Faller, Douglas V.

    2000-01-01

    We have previously reported that the long terminal repeat (LTR) region of feline leukemia viruses (FeLVs) can enhance expression of certain cellular genes such as the collagenase IV gene and MCP-1 in trans (S. K. Ghosh and D. V. Faller, J. Virol. 73:4931–4940, 1999). Genomic DNA of all healthy feline species also contains LTR-like sequences that are related to exogenous FeLV LTRs. In this study, we evaluated the cellular gene transactivational potential of these endogenous FeLV LTR sequences....

  18. B-cell leukemia/lymphoma panel

    Science.gov (United States)

    B lymphocyte cell surface markers ... sample is needed. In some cases, white blood cells are removed during a bone marrow biopsy . The ... to a laboratory, where a specialist checks the cell type and characteristics. This procedure is called immunophenotyping. ...

  19. Acute myeloid leukemia arising from a donor derived premalignant hematopoietic clone: A possible mechanism for the origin of leukemia in donor cells

    OpenAIRE

    Dickson, Mark A.; Papadopoulos, Esperanza B.; Hedvat, Cyrus V.; Jhanwar, Suresh C.; Brentjens, Renier J.

    2014-01-01

    During recent years, it has become increasingly evident that donor leukemia following allogeneic transplant may be more common then realized in the past. We identified five cases of potential donor leukemia cases during past five years. The precise mechanism of the origin of such leukemias, however, remains poorly defined. In this short communication, we report a well documented case of donor-derived de novo acute myeloid leukemia (AML) that developed fourteen years after allogeneic stem cell...

  20. Mitochondrial DNA sequence variation in single cells from leukemia patients

    OpenAIRE

    Yao, Yong-Gang; Ogasawara, Yoji; Kajigaya, Sachiko; Molldrem, Jeffrey J.; Falcão, Roberto P; Pintão, Maria-Carolina; McCoy, J. Philip; Rizzatti, Edgar Gil; Young, Neal S

    2007-01-01

    A high frequency of mtDNA somatic mutation has been observed in many tumors as well as in aging tissues. In this study, we analyzed the mtDNA control region sequence variation in 3534 single normal cells and individual blasts from 18 patients with leukemia and 10 healthy donors, to address the mutation process in leukemic cells. We found significant differences in mtDNA sequence, as represented by the number of haplotypes and the mean number of cells with each nonaggregate haplotype in a popu...

  1. Notch1-induced T cell leukemia can be potentiated by microenvironmental cues in the spleen

    OpenAIRE

    Ma, Shihui; Shi, Yingxu; Pang, Yakun; Dong, Fang; Cheng, Hui; Hao, Sha; Xu, Jing; Zhu, Xiaofan; Yuan, Weiping; Cheng, Tao; Zheng, Guoguang

    2014-01-01

    Background Leukemia is a systemic malignancy originated from hematopoietic cells. The extracellular environment has great impacts on the survival, proliferation and dissemination of leukemia cells. The spleen is an important organ for extramedullary hematopoiesis and a common infiltration site in lymphoid malignancies. Splenomegaly, frequently observed in T cell acute lymphoblastic leukemia (T-ALL), is associated with poor prognosis. However, how the spleen microenvironment distinctly affects...

  2. Feline leukemia virus and feline immunodeficiency virus infections in a cat with lymphoma.

    Science.gov (United States)

    Shelton, G H; McKim, K D; Cooley, P L; Dice, P F; Russell, R G; Grant, C K

    1989-01-15

    Lymphoma was diagnosed in a 7-year-old domestic cat found to be infected with FeLV and feline immunodeficiency virus (FIV). The cat was affected by chronic disorders suggestive of immunosuppression, including gingivitis, periodontitis, keratitis, and abscesses. Despite treatment, peripheral keratitis of the left eye progressed, resulting in uveitis, chronic glaucoma, and eventual corneal rupture. Microscopic retinal and optic disk pathologic processes also were suspected. Abnormal jaw movements that were believed to be indicative of neurologic disease were observed. Approximately 17 months later, the cat developed generalized lymphadenopathy, hepatosplenomegaly, and bilateral renomegaly. Lymphoblastic lymphoma and glomerulonephritis were diagnosed histologically. Manganese- and magnesium-dependent reverse transcriptase activity were detected in supernatants from lymph node and spleen mononuclear cell cultures, suggesting T-lymphocyte infection with FeLV and FIV. PMID:2537274

  3. Efficiency of AUY922 in mice with adult T-cell leukemia/lymphoma

    Science.gov (United States)

    ISHIKAWA, CHIE; SENBA, MASACHIKA; MORI, NAOKI

    2016-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). ATLL is associated with poor prognosis mainly due to resistance to chemotherapy, which highlights the requirement for alternative therapies. The chaperone heat shock protein (HSP) 90 assist proteins involved in the onset and progression of ATLL. In the present study, the efficacy of a second generation HSP90 inhibitor termed AUY922 was investigated in ATLL. In vitro, AUY922 induced marked inhibition of cell viability in the HTLV-1-infected T-cell lines HUT-102 and MT-4. In immunodeficient mice bearing HUT-102 xenotransplants, AUY922 markedly retarded tumor growth, compared with the control group. Apoptosis was evident in hematoxylin and eosin stained- and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling-labeled tissue sections from AUY922-treated mice. In addition, AUY922 significantly reduced the serum levels of the surrogate tumor markers soluble interleukin-2 receptor and soluble cluster of differentiation 30. Overall, the present results demonstrate that AUY922 has potent anti-ATLL activity, thus providing a rationale for continuing the clinical development of HSP90 inhibitors in clinical trials for the treatment of patients with ATLL. PMID:27347156

  4. Inhibition of Moloney murine leukemia virus-induced leukemia in transgenic mice expressing antisense RNA complementary to the retroviral packaging sequences.

    OpenAIRE

    Han, L.; Yun, J S; Wagner, T E

    1991-01-01

    Recombinant plasmids pLP psi as and pCP psi as were constructed by positioning the Moloney murine leukemia virus (M-MuLV) proviral packaging (psi) sequences in reverse orientation under the transcriptional regulation of lymphotropic promoter/regulatory elements from the M-MuLV long terminal repeat or the cytomegalovirus immediate-early region. Linear fragments containing the antisense psi and the appropriate transcriptional regulatory sequences from these plasmids were introduced into the mou...

  5. IGFBP7 induces apoptosis of acute myeloid leukemia cells and synergizes with chemotherapy in suppression of leukemia cell survival

    OpenAIRE

    Verhagen, H JMP; de Leeuw, D C; Roemer, M GM; Denkers, F; Pouwels, W; Rutten, A; Celie, P H; Ossenkoppele, G. J.; Schuurhuis, G. J.; Smit, L.

    2014-01-01

    Despite high remission rates after chemotherapy, only 30–40% of acute myeloid leukemia (AML) patients survive 5 years after diagnosis. This extremely poor prognosis of AML is mainly caused by treatment failure due to chemotherapy resistance. Chemotherapy resistance can be caused by various features including activation of alternative signaling pathways, evasion of cell death or activation of receptor tyrosine kinases such as the insulin growth factor-1 receptor (IGF-1R). Here we have studied ...

  6. Removal of xenotropic murine leukemia virus by nanocellulose based filter paper.

    Science.gov (United States)

    Asper, M; Hanrieder, T; Quellmalz, A; Mihranyan, A

    2015-11-01

    The removal of xenotrpic murine leukemia virus (xMuLV) by size-exclusion filter paper composed of 100% naturally derived cellulose was validated. The filter paper was produced using cellulose nanofibers derived from Cladophora sp. algae. The filter paper was characterized using atomic force microscopy, scanning electron microscopy, helium pycnometry, and model tracer (100 nm latex beads and 50 nm gold nanoparticles) retention tests. Following the filtration of xMuLV spiked solutions, LRV ≥5.25 log10 TCID50 was observed, as limited by the virus titre in the feed solution and sensitivity of the tissue infectivity test. The results of the validation study suggest that the nanocellulose filter paper is useful for removal of endogenous rodent retroviruses and retrovirus-like particles during the production of recombinant proteins. PMID:26328471

  7. [Typing of cattle leukemia virus circulating in the Ukraine].

    Science.gov (United States)

    Limanskiĭ, A P; Geue, L; Limanskaia, O Iu; Beier, D

    2004-01-01

    Bovine leucosis virus (BLV), circulating in the Ukrainian territory, was characterized through the definition of its subspecies affiliation. The pro-viral BLV DNA was isolated from peripheral-blood lymphocytes of naturally-HIV-infected black-variegate animals taken from leucosis-affected farms in the Kharkov Region. The env-gene fragment of pro-viral DNA was amplified, sequenced and analyzed after the amplicon had been treated by three restriction enzymes, i.e. BamH I, Bcl I and Pvu II. According to the analysis of restriction-fragments' length polymorphism, the Ukrainian BLV isolate can be classified as belonging to the Australian subspecies, i.e. to one of the 3 known subspecies. Multiple alignment and phylogenetic analysis of the env-gene fragment of BLV isolates from the EMBL database showed that evolutionally the Ukrainian isolate is distantly located from the isolates' clusters of the Belgian, Japanese and Australian subspecie and has the biggest quantity (4) of non-coinciding nucleotides for the analyzed highly conservative locus of the BLV env-gene with a length of 444 pair of nucleotides. PMID:15017853

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-11-15

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

  9. 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

  10. Sodium-Dependent myo-Inositol Transporter 1 Is a Cellular Receptor for Mus cervicolor M813 Murine Leukemia Virus

    Science.gov (United States)

    Hein, Sibyll; Prassolov, Vladimir; Zhang, Yuanming; Ivanov, Dmitry; Löhler, Jürgen; Ross, Susan R.; Stocking, Carol

    2003-01-01

    Retrovirus infection is initiated by binding of the surface (SU) portion of the viral envelope glycoprotein (Env) to specific receptors on cells. This binding triggers conformational changes in the transmembrane portion of Env, leading to membrane fusion and cell entry, and is thus a major determinant of retrovirus tissue and species tropism. The M813 murine leukemia virus (MuLV) is a highly fusogenic gammaretrovirus, isolated from Mus cervicolor, whose host range is limited to mouse cells. To delineate the molecular mechanisms of its restricted host range and its high fusogenic potential, we initiated studies to characterize the cell surface protein that mediates M813 infection. Screening of the T31 mouse-hamster radiation hybrid panel for M813 infectivity localized the receptor gene to the distal end of mouse chromosome 16. Expression of one of the likely candidate genes (slc5a3) within this region in human cells conferred susceptibility to both M813 infection and M813-induced fusogenicity. slc5a3 encodes sodium myo-inositol transporter 1 (SMIT1), thus adding another sodium-dependent transporter to the growing list of proteins used by MuLVs for cell entry. Characterization of SMIT1 orthologues in different species identified several amino acid variations within two extracellular loops that may restrict susceptibility to M813 infection. PMID:12719585

  11. Seroprevalence of feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) in shelter cats on the island of Newfoundland, Canada

    OpenAIRE

    Munro, Hannah J.; Berghuis, Lesley; Lang, Andrew S.; Rogers, Laura; Whitney, Hugh

    2014-01-01

    Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are retroviruses found within domestic and wild cat populations. These viruses cause severe illnesses that eventually lead to death. Housing cats communally for long periods of time makes shelters at high risk for virus transmission among cats. We tested 548 cats from 5 different sites across the island of Newfoundland for FIV and FeLV. The overall seroprevalence was 2.2% and 6.2% for FIV and FeLV, respectively. Two sites ha...

  12. Ethyl Pyruvate Combats Human Leukemia Cells but Spares Normal Blood Cells.

    Science.gov (United States)

    Birkenmeier, Gerd; Hemdan, Nasr Y A; Kurz, Susanne; Bigl, Marina; Pieroh, Philipp; Debebe, Tewodros; Buchold, Martin; Thieme, Rene; Wichmann, Gunnar; Dehghani, Faramarz

    2016-01-01

    Ethyl pyruvate, a known ROS scavenger and anti-inflammatory drug was found to combat leukemia cells. Tumor cell killing was achieved by concerted action of necrosis/apoptosis induction, ATP depletion, and inhibition of glycolytic and para-glycolytic enzymes. Ethyl lactate was less harmful to leukemia cells but was found to arrest cell cycle in the G0/G1 phase. Both, ethyl pyruvate and ethyl lactate were identified as new inhibitors of GSK-3β. Despite the strong effect of ethyl pyruvate on leukemia cells, human cognate blood cells were only marginally affected. The data were compiled by immune blotting, flow cytometry, enzyme activity assay and gene array analysis. Our results inform new mechanisms of ethyl pyruvate-induced cell death, offering thereby a new treatment regime with a high therapeutic window for leukemic tumors. PMID:27579985

  13. Microenvironmental cues for T-cell acute lymphoblastic leukemia development.

    Science.gov (United States)

    Passaro, Diana; Quang, Christine Tran; Ghysdael, Jacques

    2016-05-01

    Intensive chemotherapy regimens have led to a substantial improvement in the cure rate of patients suffering from T-cell acute lymphoblastic leukemia (T-ALL). Despite this progress, about 15% and 50% of pediatric and adult cases, respectively, show resistance to treatment or relapse with dismal prognosis, calling for further therapeutic investigations. T-ALL is an heterogeneous disease, which presents intrinsic alterations leading to aberrant expression of transcription factors normally involved in hematopoietic stem/progenitor cell development and mutations in genes implicated in the regulation of cell cycle progression, apoptosis, and T-cell development. Gene expression profiling allowed the classification of T-ALL into defined molecular subgroups that mostly reflects the stage of their differentiation arrest. So far this knowledge has not translated into novel, targeted therapy. Recent evidence points to the importance of extrinsic signaling cues in controlling the ability of T-ALL to home, survive, and proliferate, thus offering the perspective of new therapeutic options. This review summarizes the present understanding of the interactions between hematopoietic cells and bone marrow/thymic niches during normal hematopoiesis, describes the main signaling pathways implicated in this dialog, and finally highlights how malignant T cells rely on specific niches to maintain their ability to sustain and propagate leukemia. PMID:27088913

  14. Reversal by Dithiothreitol Treatment of the Block in Murine Leukemia Virus Maturation Induced by Disulfide Cross-Linking

    OpenAIRE

    Campbell, Stephen; Oshima, Masamichi; Mirro, Jane; Nagashima, Kunio; Rein, Alan

    2002-01-01

    We previously reported that if murine leukemia virus particles are produced in the presence of the mild oxidizing agent disulfide-substituted benzamide-2, they fail to undergo the normal process of virus maturation. We now show that treatment of these immature particles with a reducing agent (dithiothreitol) induces their maturation in vitro, as evidenced by proteolytic cleavage of Gag, Gag-Pol, and Env proteins and by their morphology. The identification of partial cleavage products in these...

  15. Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia

    OpenAIRE

    Guenther, Matthew G.; Lawton, Lee N.; Rozovskaia, Tatiana; Frampton, Garrett M.; Levine, Stuart S.; Thomas L Volkert; Croce, Carlo M.; Nakamura, Tatsuya; Canaani, Eli; Young, Richard A.

    2008-01-01

    Mixed-lineage leukemia (MLL) fusion proteins are potent inducers of leukemia, but how these proteins generate aberrant gene expression programs is poorly understood. Here we show that the MLL-AF4 fusion protein occupies developmental regulatory genes important for hematopoietic stem cell identity and self-renewal in human leukemia cells. These MLL-AF4-bound regions have grossly altered chromatin structure, with histone modifications catalyzed by trithorax group proteins and DOT1 extending acr...

  16. Unrelated Hematopoietic Stem Cell Transplantation for Children with Acute Leukemia: Experience at a Single Institution

    OpenAIRE

    Lee, Jae Hee; Yoon, Hoi Soo; Song, Joon Sup; Choi, Eun Seok; Moon, Hyung Nam; Seo, Jong Jin; Im, Ho Joon

    2009-01-01

    We evaluate the outcomes in children with acute leukemia who received allogeneic hematopoietic stem cell transplantation (HCT) using unrelated donor. Fifty-six children in complete remission (CR) received HCT from unrelated donors between 2000 and 2007. Thirty-five had acute myeloid leukemia, and 21 had acute lymphoid leukemia. Stem cell sources included bone marrow in 38, peripheral blood in 4, and cord blood (CB) in 14. Four patients died before engraftment and 52 engrafted. Twenty patients...

  17. Epidemiology, infection dynamics and effective control of Bovine Leukemia virus within dairy herds of Argentina: a quantitative approach

    NARCIS (Netherlands)

    Monti, G.E.

    2005-01-01

    Bovine Leukemia Virus (BLV) is a retrovirus that causes lymphomas (leucosis) and other disorders in cattle and it has a large economical impact on the livestock sector of many countries around the world. BovineParameters of disease progression in long-term experimental feline retrovirus (feline immunodeficiency virus and feline leukemia virus) infections: hematology, clinical chemistry, and lymphocyte subsets.

    OpenAIRE

    Hofmann-Lehmann, R.; Holznagel, E; Ossent, P.; Lutz, H.

    1997-01-01

    After several years of latency, feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) cause fatal disease in the cat. The aim of this study was to determine laboratory parameters characteristic of disease progression which would allow a better description of the asymptomatic phase and a better understanding of the pathogenesis of the two infections. Therefore, experimentally infected cats (FIV and/or FeLV positive) and control animals were observed over a period of 6.5 years un...

  18. Comparison of the geographical distribution of feline immunodeficiency virus and feline leukemia virus infections in the United States of America (2000–2011)

    OpenAIRE

    Chhetri Bimal K; Berke Olaf; Pearl David L; Bienzle Dorothee

    2013-01-01

    Abstract Background Although feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) have similar risk factors and control measures, infection rates have been speculated to vary in geographic distribution over North America. Since both infections are endemic in North America, it was assumed as a working hypothesis that their geographic distributions were similar. Hence, the purpose of this exploratory analysis was to investigate the comparative geographical distribution of both v...

  19. Feline leukemia virus infection as a potentiating cofactor for the primary and secondary stages of experimentally induced feline immunodeficiency virus infection.

    OpenAIRE

    Pedersen, N C; Torten, M.; Rideout, B; Sparger, E; Tonachini, T; Luciw, P A; Ackley, C; Levy, N.; Yamamoto, J.

    1990-01-01

    Preexistent feline leukemia virus (FeLV) infection greatly potentiated the severity of the transient primary and chronic secondary stages of feline immunodeficiency virus (FIV) infection. Of 10 FeLV-FIV carrier cats, 5 died of experimentally induced FIV infection, compared with 2 deaths in 10 cats infected only with FeLV and 1 death in 7 cats infected only with FIV. FIV-infected cats with preexistent FeLV infections developed severe depression, anorexia, fever, diarrhea, dehydration, weight l...

  1. Comparison of risk factors for seropositivity to feline immunodeficiency virus and feline leukemia virus among cats: a case-case study

    OpenAIRE

    Chhetri, Bimal K.; Berke, Olaf; Pearl, David L.; Bienzle, Dorothee

    2015-01-01

    Background Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are reported to have similar risk factors and similar recommendations apply to manage infected cats. However, some contrasting evidence exists in the literature with regard to commonly reported risk factors. In this study, we investigated whether the known risk factors for FIV and FeLV infections have a stronger effect for either infection. This retrospective study included samples from 696 cats seropositive for F...

  2. Seroprevalences of antibodies against bovine leukemia virus, bovine viral diarrhea virus, Mycobacterium avium subspecies paratuberculosis, and Neospora caninum in beef and dairy cattle in Manitoba

    OpenAIRE

    Vanleeuwen, John A.; Tiwari, Ashwani; Plaizier, Jan C; Whiting, Terry L.

    2006-01-01

    Of 1204 dairy cows and 1425 beef cows sampled, 60.8% and 10.3% were seropositive for Bovine leukemia virus, 4.5% and 1.7% were seropositive for Mycobacterium avium subspecies paratuberculosis, and 8.3% and 9.1% were seropositive for Neospora caninum, respectively, while 28.1% of dairy herds had unvaccinated animals with titres ≥ 1:64 for Bovine viral diarrhea virus.

  3. Murine leukemia virus-based Tat-inducible long terminal repeat replacement vectors: a new system for anti-human immunodeficiency virus gene therapy.

    Science.gov (United States)

    Cannon, P M; Kim, N; Kingsman, S M; Kingsman, A J

    1996-11-01

    We have constructed new murine leukemia virus (MLV)-based vectors (TIN vectors) which, following integration, contain human immunodeficiency virus (HIV) type 1 U3 and R sequences in place of the MLV U3 and R regions. This provides, for the first time, single transcriptional unit retroviral vectors under the control of Tat. TIN vectors have several advantages for anti-HIV gene therapy applications. PMID:8892960

  4. Murine leukemia virus-based Tat-inducible long terminal repeat replacement vectors: a new system for anti-human immunodeficiency virus gene therapy.

    OpenAIRE

    Cannon, P M; Kim, N.; Kingsman, S M; Kingsman, A J

    1996-01-01

    We have constructed new murine leukemia virus (MLV)-based vectors (TIN vectors) which, following integration, contain human immunodeficiency virus (HIV) type 1 U3 and R sequences in place of the MLV U3 and R regions. This provides, for the first time, single transcriptional unit retroviral vectors under the control of Tat. TIN vectors have several advantages for anti-HIV gene therapy applications.

  5. Characterization of Ebola Virus Entry by Using Pseudotyped Viruses: Identification of Receptor-Deficient Cell Lines

    OpenAIRE

    Wool-Lewis, Rouven J.; Bates, Paul

    1998-01-01

    Studies analyzing Ebola virus replication have been severely hampered by the extreme pathogenicity of this virus. To permit analysis of the host range and function of the Ebola virus glycoprotein (Ebo-GP), we have developed a system for pseudotyping these glycoproteins into murine leukemia virus (MLV). This pseudotyped virus, MLV(Ebola), can be readily concentrated to titers which exceed 5 × 106 infectious units/ml and is effectively neutralized by antibodies specific for Ebo-GP. Analysis of ...

  6. Characterization of xenoantiserum produced against B cell acute lymphoblastic leukemia cell line

    Directory of Open Access Journals (Sweden)

    Akagi,Tadaatsu

    1982-10-01

    Full Text Available Antiserum was produced in white rabbit by intravenously injecting living cells of a B cell acute lymphoblastic leukemia (ALL line (BALL-1. The reactivity of the antiserum against various lymphoid cell lines was examined by membrane immunofluorescence after appropriate absorption. Serum absorbed with non-T, non-B (NALL-1 and T-ALL (TALL-1 cells recognized B cell antigens distinct from Ia-like antigens on both normal and neoplastic B cells. After further absorption with tonsillar cells or normal B cell line (KO-HL-3, it reacted only with BALL-1 cells and did not react with other leukemia/lymphoma and normal B cell lines. The serum absorbed with tonsillar cells reacted only with BALL-1 and some B cell lines. Thus we were able to obtain antisera with specificity to B cell antigen, B-ALL antigen, and B cell line antigen.

  7. B-cell leukemia/lymphoma panel

    Science.gov (United States)

    ... is broken) Alternative Names B lymphocyte cell surface markers Images Blood test References Czuchlewski DR, Viswanatha DS, Larson RS. Molecular diagnosis of hematopoietic neoplasms. In: McPherson RA, Pincus ...

  8. Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol

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    Okudaira Taeko

    2009-01-01

    Full Text Available Abstract Background Adult T-cell leukemia/lymphoma (ATLL is a malignancy derived from T cells infected with human T-cell leukemia virus type 1 (HTLV-1, and it is known to be resistant to standard anticancer therapies. Indole-3-carbinol (I3C, a naturally occurring component of Brassica vegetables such as cabbage, broccoli and Brussels sprout, is a promising chemopreventive agent as it is reported to possess antimutagenic, antitumorigenic and antiestrogenic properties in experimental studies. The aim of this study was to determine the potential anti-ATLL effects of I3C both in vitro and in vivo. Results In the in vitro study, I3C inhibited cell viability of HTLV-1-infected T-cell lines and ATLL cells in a dose-dependent manner. Importantly, I3C did not exert any inhibitory effect on uninfected T-cell lines and normal peripheral blood mononuclear cells. I3C prevented the G1/S transition by reducing the expression of cyclin D1, cyclin D2, Cdk4 and Cdk6, and induced apoptosis by reducing the expression of XIAP, survivin and Bcl-2, and by upregulating the expression of Bak. The induced apoptosis was associated with activation of caspase-3, -8 and -9, and poly(ADP-ribose polymerase cleavage. I3C also suppressed IκBα phosphorylation and JunD expression, resulting in inactivation of NF-κB and AP-1. Inoculation of HTLV-1-infected T cells in mice with severe combined immunodeficiency resulted in tumor growth. The latter was inhibited by treatment with I3C (50 mg/kg/day orally, but not the vehicle control. Conclusion Our preclinical data suggest that I3C could be potentially a useful chemotherapeutic agent for patients with ATLL.

  9. Characterization of xenoantiserum produced against B cell acute lymphoblastic leukemia cell line

    OpenAIRE

    Akagi,Tadaatsu; Sonobe, Hiroshi; Miyoshi, Isao; Yoshimoto,Shizuo

    1982-01-01

    Antiserum was produced in white rabbit by intravenously injecting living cells of a B cell acute lymphoblastic leukemia (ALL) line (BALL-1). The reactivity of the antiserum against various lymphoid cell lines was examined by membrane immunofluorescence after appropriate absorption. Serum absorbed with non-T, non-B (NALL-1) and T-ALL (TALL-1) cells recognized B cell antigens distinct from Ia-like antigens on both normal and neoplastic B cells. After further absorption with tonsillar cells or n...

  10. A human TRIM5α B30.2/SPRY domain mutant gains the ability to restrict and prematurely uncoat B-tropic murine leukemia virus

    OpenAIRE

    Diaz-Griffero, Felipe; Perron, Michel; McGee-Estrada, Kathleen; Hanna, Robert; Maillard, Pierre; Trono, Didier; Sodroski, Joseph

    2008-01-01

    Human TRIM5α restricts N-tropic murine leukemia virus (N-MLV) but not B-tropic MLV (B-MLV) infection. Here we study B30.2/SPRY domain mutants of human TRIM5α that acquire the ability to inhibit B-MLV infection prior to reverse transcription without losing the ability to restrict N-MLV infection. Remarkably, these mutants gain the ability to decrease the amount of particulate B-MLV capsids in the cytosol of infected cells. In addition, these mutants gain the ability to restrict SIVmac and HIV-...

  11. Detection of phosphorylated forms of Moloney murine leukemia virus major capsid protein p30 by immunoprecipitation and two-dimensional gel electrophoresis.

    OpenAIRE

    Ikuta, K.; Luftig, R B

    1988-01-01

    We detected phosphorylation of the major Moloney murine leukemia virus (M-MuLV) capsid polypeptide, p30, by using 32Pi-labeled virions. This was observed both on two-dimensional polyacrylamide gels directly or on one-dimensional gels of viral lysates that had been immunoprecipitated with monospecific goat anti-p30 serum. The phosphorylation event had been difficult to detect because pp12 the major virion phosphoprotein incorporates almost all of the 32P label added to infected cells (Y. Yoshi...

  12. IGF binding protein 2 is a cell-autonomous factor supporting survival and migration of acute leukemia cells

    OpenAIRE

    Chen, Xiaoli; Zheng, Junke; Zou, Yizhou; Song, Chun; Hu, Xuemei; Zhang, Cheng Cheng

    2013-01-01

    Background The role of IGF binding protein 2 (IGFBP2) in cancer development is intriguing. Previously we identified IGFBP2 as an extrinsic factor that supports the activity of hematopoietic stem cells (HSCs). Methods and results Here we investigated the role of IGFBP2 in in human leukemia cells and in the retroviral AML1-ETO9a transplantation acute myeloid leukemia (AML) mouse model. Results IGFBP2 is highly expressed in certain human AML and acute lymphoblastic leukemia (ALL) cells. Inhibiti...

  13. Aberrant Expression of Functional BAFF-System Receptors by Malignant B-Cell Precursors Impacts Leukemia Cell Survival

    OpenAIRE

    Maia, Sara; Pelletier, Marc; Ding, Jixin; Hsu, Yen-Ming; Rao, Sambasiva P.; Cardoso, Angelo A.; Sallan, Stephen Earl; Nadler, Lee Marshall

    2011-01-01

    Despite exhibiting oncogenic events, patient's leukemia cells are responsive and dependent on signals from their malignant bone marrow (BM) microenvironment, which modulate their survival, cell cycle progression, trafficking and resistance to chemotherapy. Identification of the signaling pathways mediating this leukemia/microenvironment interplay is critical for the development of novel molecular targeted therapies. We observed that primary leukemia B-cell precursors aberrantly express recept...

  14. Molecular basis of a unique tumor antigen of radiation leukemia virus-induced leukemia B6RV2: its relation to MuLV gp70 of xenotropic class

    International Nuclear Information System (INIS)

    Hybridomas secreting monoclonal antibodies that reacted with the B6 radiation leukemia virus (RadLV)-induced leukemia B6RV2 were produced by fusion of BALB/c NS-1 myeloma cells with spleen cells from (BALB/c X B6)F1 mice immunized with B6RV2. By direct and absorption analyses with 28 B6 and BALB/c leukemias, the monoclonal antibodies NU7-4 and NU7-99 were shown to react only with B6RV2, indicating that they recognized an individually distinct antigen on B6RV2 that was identified previously with conventional (BALB/c X B6)F1 anti-B6RV2 serum. Another monoclonal antibody, NU1-132, showed relatively restricted reactivity with B6 RadLV leukemias. These three monoclonal antibodies all precipitated material of approximately 80,000 daltons, which is the same size as that precipitated by anti-xenotropic MuLV gp70 serum. Sequential immunoprecipitation analysis revealed that the molecules precipitated by NU7-4 were not removed by pretreatment of NU7-99 or NU1-132 and that the molecules precipitated by NU7-99 were not removed by NU7-4 or NU1-132. The molecules precipitated by NU1-132 were partially removed by pretreatment with NU7-4, but not with NU7-99. The molecules precipitated by these three monoclonal antibodies were removed by pretreatment with anti-xenotropic gp70. These results suggested heterogeneity of the xenotropic MuLV gp70-related molecules expressed on B6RV2 and a possible relation between serologically defined unique tumor antigens and gp70-related molecules

  15. Respiratory syncytial virus infection in infants with acute leukemia: a retrospective survey of the Japanese Pediatric Leukemia/Lymphoma Study Group.

    Science.gov (United States)

    Hatanaka, Michiki; Miyamura, Takako; Koh, Katsuyoshi; Taga, Takashi; Tawa, Akio; Hasegawa, Daisuke; Kajihara, Ryosuke; Adachi, Souichi; Ishii, Eiichi; Tomizawa, Daisuke

    2015-12-01

    Respiratory syncytial virus (RSV) can cause life-threatening complications of lower respiratory tract infection (LRTI) in young children with malignancies, but reports remain limited. We performed a retrospective nationwide survey to clarify the current status of RSV disease among infants with hematological malignancies. Clinical course, treatment, and outcome of patients with hematological malignancies who suffered from RSV infections at the age of Leukemia/Lymphoma Study Group (JPLSG). Twelve patients with acute leukemia were identified as having experienced RSV disease. The primary diseases were acute myeloid leukemia (n = 8) and acute lymphoblastic leukemia (n = 4). RSV infection occurred pre- or during induction therapy (n = 8) and during consolidation therapy (n = 4). Eight patients developed LRTI, four of whom had severe pneumonia or acute respiratory distress syndrome; these four patients died despite receiving intensive care. In our survey, the prognosis of RSV disease in pediatric hematological malignancies was poor, and progression of LRTI in particular was associated with high mortality. In the absence of RSV-specific therapy, effective prevention and treatment strategies for severe RSV disease must be investigated. PMID:26520649

  16. CD117 expression on blast cells in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Goryainova N.V.

    2015-09-01

    Full Text Available The aim of the present work was to analyze the frequency of CD117 (c-KIT antigen expression on the blast cells in acute myeloid leukemia (AML, evaluation of the presence of the relationship between the expression of the c-KIT and leukemia according to the FAB classification and definition of co-expression of the antigen CD117, antigens CD33 and CD34. The data of 47 patients with AML were diagnosed. M0 AML variant was established in 3 (6% patients, M1 – in 2 (4%, M2 – in 9 (20%, M4 – in 22 (47% and M5 – in 11 (23%. For immunophenotypic stu¬dies monoclonal antibodies (mAb that detect antigens of anti-CD34, anti-CD33 and anti-CD117 (Becton Dickinson, USA were used. The presence of the antigen CD117 was detected in 39 people, accounting for 83% of all surveyed. Antigen c-KIT was present in 48.117.0% cells on average: in all 3 cases – AML M0, in2 cases of AML M1, in 6 cases – AML M2, 20 of 22 cases – AML M4 and in 8 of 11 AML M5 cases. Average levels of CD117 in investigated leukemia cases statistically differed significantly (p=0.0067. Among 39 CD117- positive patients in 25 (53% co-expression of CD117+/CD34+ was revealed. Expression of CD117+/CD34- was observed in 14 cases (30%, CD117-/CD34+ – in 4 cases (8,5%, CD117-/CD34- – in 4 cases (8.5%. CD34 had of 64% of cells of myeloid origin. A high positive cor¬relation between expression of CD117 and CD34 (r=+0,5169 was determined, being statistically significant (p0,0067.

  17. Two discrete events, human T-cell leukemia virus type I Tax oncoprotein expression and a separate stress stimulus, are required for induction of apoptosis in T-cells

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    Kasai Takefumi

    2004-05-01

    Full Text Available Abstract Background It is poorly understood why many transforming proteins reportedly enhance both cell growth (transformation and cell death (apoptosis. At first glance, the ability to transform and the ability to engender apoptosis seem to be contradictory. Interestingly, both abilities have been widely reported in the literature for the HTLV-I Tax protein. Results To reconcile these apparently divergent findings, we sought to understand how Tax might cause apoptosis in a Jurkat T-cell line, JPX-9. Tax expression can be induced equally by either cadmium (Cd or zinc (Zn in JPX-9 cells. Surprisingly, when induced by Zn, but not when induced by Cd, Tax-expression produced significant apoptosis. Under our experimental conditions, Zn but not Cd, induced SAPK (stress activated protein kinase/JNK (Jun kinase activation in cells. We further showed that transient over-expression of Tax-alone or Jun-alone did not induce cell death. On the other hand, co-expression of Tax plus Jun did effectively result in apoptosis. Conclusion We propose that Tax-expression alone in a T-cell background insufficiently accounts for apoptosis. On the other hand, Tax plus activation of a stress kinase can induce cell death. Thus, HTLV-I infection/transformation of cells requires two discrete events (i.e. oncoprotein expression and stress to produce apoptosis.

  18. Blocking p55PIK signaling inhibits proliferation and induces differentiation of leukemia cells.

    Science.gov (United States)

    Wang, G; Deng, Y; Cao, X; Lai, S; Tong, Y; Luo, X; Feng, Y; Xia, X; Gong, J; Hu, J

    2012-11-01

    p55PIK, a regulatory subunit of phosphatidylinositol 3-kinases, promotes cell cycle progression by interacting with cell cycle modulators such as retinoblastoma protein (Rb) via its unique amino-terminal 24 amino-acid residue (N24). Overexpression of N24 specifically inhibits these interactions and leads to cell cycle arrest. Herein, we describe the generation of a fusion protein (Tat transactivator protein (TAT)-N24) that contains the protein transduction domain and N24, and examined its effects on the proliferation and differentiation of leukemia cells. TAT-N24 not only blocks cell proliferation but remarkably induces differentiation of leukemia cells in vitro and in vivo. Systemically administered TAT-N24 also significantly decreases growth of leukemia cell tumors in animal models. Furthermore, overexpression of p55PIK in leukemia cells leads to increased proliferation; however, TAT-N24 blocks this effect and concomitantly induces differentiation. There is significant upregulation of p55PIK mRNA and protein expression in leukemia cells from patients. TAT-N24 inhibits cell cycle progression and induces differentiation of bone marrow cells derived from patients with several different types of leukemia. These results show that cell-permeable N24 peptide induces leukemia cell differentiation and suggest that p55PIK may be a novel drug target for the treatment of hematopoetic malignancies. PMID:22722333

  19. A Case Report of Hairy Cell Leukemia Presenting Concomitantly with Sweet Syndrome

    OpenAIRE

    Mohammad Alkayem; Waina Cheng

    2014-01-01

    Hairy cell leukemia and Sweet syndrome are both uncommon hematological diagnoses. We present a patient who was admitted with fevers, pancytopenia, pneumonia, and rash. Diagnostic bone marrow biopsy demonstrates Hairy cell Leukemia and skin biopsy demonstrates neutrophils infiltration consistent with Sweet syndrome. The patient was treated with purine analogs with resolution of the cytopenias, infection, and rash.

  20. A Case Report of Hairy Cell Leukemia Presenting Concomitantly with Sweet Syndrome

    Directory of Open Access Journals (Sweden)

    Mohammad Alkayem

    2014-01-01

    Full Text Available Hairy cell leukemia and Sweet syndrome are both uncommon hematological diagnoses. We present a patient who was admitted with fevers, pancytopenia, pneumonia, and rash. Diagnostic bone marrow biopsy demonstrates Hairy cell Leukemia and skin biopsy demonstrates neutrophils infiltration consistent with Sweet syndrome. The patient was treated with purine analogs with resolution of the cytopenias, infection, and rash.

  1. Advanced lymphoblastic clones detection in T-cell leukemia.

    Science.gov (United States)

    Minervina, A A; Komkov, A Y; Mamedov, I Z; Lebedev, Y B

    2016-03-01

    T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignant neoplasm of the lymphocyte precursors that suffered malignant transformation arresting the lymphoid cell differentiation. Clinical studies revealed monoor, more rarely, oligoclonal nature of the disease. A precise identification of malignant clone markers is both the crucial stage of early diagnostics and the essential prognostic factor for therapeutic treatment. Here we present an improved system for unbiased detection of lymphoblastic clones in bone marrow aspirates of T-ALL patients. The system based on multiplex PCR of rearranged T-cell receptor locus (TRB) and straightforward sequencing of the resulted PCR fragments. Testing of the system on genomic DNA from Jurkat cell line and four clinical bone marrow aspirates revealed a set of unique TRB rearrangements that precisely characterize each of tested samples. Therefore, the outcome of the system produces highly informative molecular genetic markers for further monitoring of minimal residual disease in T-ALL patients. PMID:27193704

  2. 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

  3. Current status of haploidentical stem cell transplantation for leukemia

    Directory of Open Access Journals (Sweden)

    Huang Xiao-jun

    2008-12-01

    Full Text Available Abstract Haploidentical hematopoietic stem cell transplantation has made tremendous progress over the past 20 years and has become a feasible option for leukemia patients without a HLA identical sibling donor. The early complications of severe graft-versus-host disease (GVHD, graft failure and delayed engraftment, as well as disease recurrence have limited the use of this approach. Newer strategies have been applied and overcome some of the problems, including the use of T-cell depleted graft, "mega" dose of stem cells, intensive post-transplant immunosuppression and manipulation of the graft. These have decreased the transplant related mortality and GVHD associated with haploidentical transplantation, however, the major problems of disease relapse and infection, which related to late immune reconstitution, limit the development of haploidentical HSCT. Future challenges remain in improving post-transplant immune reconstitution and finding the best approach to reduce the incidence and severity of GVHD, while preserving graft-versus-leukemia effect to prevent the recurrence of underlying malignancy.

  4. Mutagenesis analysis of the murine leukemia virus matrix protein: identification of regions important for membrane localization and intracellular transport.

    OpenAIRE

    Soneoka, Y; Kingsman, S M; Kingsman, A J

    1997-01-01

    We have created two sets of substitution mutations in the Moloney murine leukemia virus (Mo-MuLV) matrix protein in order to identify domains involved in association with the plasma membrane and in incorporation of the viral envelope glycoproteins into virus particles. The first set of mutations was targeted at putative membrane-associating regions similar to those of the human immunodeficiency virus type 1 matrix protein, which include a polybasic region at the N terminus of the Mo-MuLV matr...

  5. Absence of XMRV and Closely Related Viruses in Primary Prostate Cancer Tissues Used to Derive the XMRV-Infected Cell Line 22Rv1

    OpenAIRE

    Das Gupta, Jaydip; Luk, Ka-Cheung; Tang, Ning; Gaughan, Christina; Klein, Eric A.; Kandel, Eugene S.; Hackett, John; Silverman, Robert H.

    2012-01-01

    The 22Rv1 cell line is widely used for prostate cancer research and other studies throughout the world. These cells were established from a human prostate tumor, CWR22, that was serially passaged in nude mice and selected for androgen independence. The 22Rv1 cells are known to produce high titers of xenotropic murine leukemia virus-related virus (XMRV). Recent studies suggested that XMRV was inadvertently created in the 1990's when two murine leukemia virus (MLV) genomes (pre-XMRV1 and pre-XM...

  6. Cell biological effects of total body irradiation on growth and differentiation of acute myelogenous leukemia cells compared to normal bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Greenberger, J.S.; Weichselbaum, R.R.; Botnick, L.E.; Sakakeeny, M.; Moloney, W.C.

    1979-01-01

    Radiation therapy is used as total body treatment in preparation of the acute myelogenous leukemia (AML) patient for bone marrow transplantation. Many AML patients will have residual leukemia cells at the time of total body irradiation (TBI). In the present study, the effect of TBI on leukemic myeloid cells was compared to the effect on normal marrow granulocytic stem cells (CFUc) in vitro. Little difference from that of normal CFUc was found in the radiosensitivity of two mouse myeloid leukemia cell lines. The effect of TBI on growth of WEHI-3 or J774 cells in millipore diffusion chambers was stimulatory. These AML cell lines as well as others derived from Friend or Abelson virus infected in vitro long term mouse marrow cultures showed some morphologic differentiation by 7 days growth in diffusion chambers in irradiated heterologous rat hosts, but immature cells predominated by day 21. Thus, evidence in murine models of AML indicates that residual AML cells surviving chemotherapy will show no greater susceptibility to radiation killing compared to normal stem cells and will rapidly repopulate the irradiated host.

  7. Mechanism of infectivity of a murine leukemia virus in adult mice

    International Nuclear Information System (INIS)

    Infection of adult BALB/c mice with murine leukemia virus (MuLV) induces typical thymic lymphomas. Expression of virus was measured by using a radioimmunoassay for murine P-30, a virion core protein. Nineteen days after injection of MuLV-S into adult mice, there were 0.3μg P-30/ml of serum. X-irradiation permitted the early expression of high levels of viremia, when given before or after MuLV-S administration, and it also hastened the development of lymphomas. Seventeen to 21 days after injection of MuLV-S into x-irradiated (600 rads) adult mice, there were 2.7 μg of P-30/ml of serum. The virus produced by infected adult mice was infectious and oncogenic when given to newborn mice. Several lines of evidence are presented that suggest the mechanism by which x-irradiation permits early expession of virion proteins and lymphomas is not immunosuppression

  8. Estimation of bovine leukemia virus (BLV) proviral load harbored by lymphocyte subpopulations in BLV-infected cattle at the subclinical stage of enzootic bovine leucosis using BLV-CoCoMo-qPCR

    OpenAIRE

    Panei, Carlos Javier; Takeshima, Shin-nosuke; Omori, Takashi; NUNOYA, Tetsuo; Davis, William C.; Ishizaki, Hiroshi; Matoba, Kazuhiro; Aida, Yoko

    2013-01-01

    Background Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis (EBL), which is the most common neoplastic disease of cattle. BLV infection may remain clinically silent at the aleukemic (AL) stage, cause persistent lymphocytosis (PL), or, more rarely, B cell lymphoma. BLV has been identified in B cells, CD2+ T cells, CD3+ T cells, CD4+ T cells, CD8+ T cells, γ/δ T cells, monocytes, and granulocytes in infected cattle that do not have tumors, although the most consistently i...

  9. Mutational analysis of the putative receptor-binding domain of Moloney murine leukemia virus glycoprotein gp70.

    Science.gov (United States)

    Panda, B R; Kingsman, S M; Kingsman, A J

    2000-07-20

    The entry of Moloney murine leukemia virus (MoMuLV) to murine cells is mediated by the binding of its envelope glycoprotein gp70 to its receptor, the cationic amino acid transporter MCAT-1. The binding property of the envelope protein lies mainly in the N-terminal half of the protein. To identify essential residues involved in the binding of gp70 to its receptor, we have mutated amino acids within the putative receptor-binding domain of MoMuLV gp70. Changes in the residues P94 and W100 resulted in lower viral titers in comparison to the wild-type virions. Single, double, or triple point mutations involving the residue W100 make the envelope protein severely defective in binding to its receptor. Binding studies and cell fusion experiments with murine XC cells suggested that the residue W100 might play an important role in the process of infection by making contact between gp70 and its receptor. PMID:10891411

  10. Cordycepin regulates GSK-3β/β-catenin signaling in human leukemia cells.

    Directory of Open Access Journals (Sweden)

    Bor-Sheng Ko

    Full Text Available BACKGROUND: Leukemia stem cells (LSCs are a limitless cell source for the initiation and maintenance of leukemia. Activation of the Wnt/β-catenin pathway is required for the survival and development of LSCs. Therefore, targeting β-catenin is considered a therapeutic strategy for the treatment of leukemia. The goal of this study was to explore whether cordycepin, an active component of the traditional medicine Cordyceps sinensis, regulates β-catenin expression in leukemia cells. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, we found that cordycepin significantly suppressed cell proliferation in all malignant cancer cells, including U937, K562, A549, HepG2, SK-Hep1 and MCF7 in a dose-dependent manner. However, cordycepin reduced β-catenin levels in U937, K562 and THP1 leukemia cells and had no effect on other solid cancer cells. In addition, treatment with cordycepin significantly suppressed leukemia colony formation in soft agar assay. Cordycepin enhanced proteasome-dependent degradation and inhibited nuclear translocation of β-catenin in leukemia cells. Cordycepin-reduced β-catenin stability was restored by the addition of a pharmacological inhibitor of GSK-3β, indicating that cordycepin-suppressed β-catenin stability is mediated by the activation of GSK-3β. Furthermore, cordycepin abolished the effect of Wnt3a-induced β-catenin in leukemia cells. In addition, cordycepin-impaired β-catenin is regulated by Akt activation but is not significantly influenced by AMPK or mTOR signal pathways. SIGNIFICANCE: Our findings show for the first time that codycepin selectively reduces β-catenin stability in leukemia but not in other solid tumor cells. This suppressive effect is mediated by regulating GSK-3β. A synergistic combination of cordycepin with other treatments should be used as a novel strategy to eradicate leukemia via elimination of LSCs.

  11. Diseases associated with spontaneous feline leukemia virus (FeLV) infection in cats.

    Science.gov (United States)

    Reinacher, M

    1989-05-01

    More than 2000 cats sent for necropsy in order to provide a diagnosis were investigated immunohistologically using paraffin sections for the presence of a persistent infection with feline leukemia virus (FeLV). The spectrum of neoplastic and non-neoplastic diseases associated significantly with FeLV infection was determined statistically. Three-quarters of the cats with persistent FeLV infections died of non-neoplastic diseases and about 23% died of tumors, nearly exclusively those of the leukemia/lymphoma disease complex. A strong association with liver degeneration, icterus and a FeLV-associated enteritis was found in addition to the known association with non-neoplastic diseases and conditions such as anemia, bacterial secondary infections and respiratory tract inflammations due to the immunosuppressive effect of FeLV, hemorrhages and feline infectious peritonitis. Surprisingly, diseases and conditions like feline infectious panleukopenia, enteritis (of other types than FeLV-associated enteritis and feline infectious panleukopenia), glomerulonephritis, uremia and hemorrhagic cystitis were not associated with persistent FeLV infection. Another unexpected finding was that most pathogenic infectious agents demonstrated in the cats were not FeLV-associated either. Thus, immunosuppression due to FeLV infection seems to make the animals susceptible to certain pathogenic infectious agents, but not to the majority. PMID:2549696

  12. Complete suppression of viral gene expression is associated with the onset and progression of lymphoid malignancy: observations in Bovine Leukemia Virus-infected sheep

    Directory of Open Access Journals (Sweden)

    Burny Arsène

    2007-07-01

    Full Text Available Abstract Background During malignant progression, tumor cells need to acquire novel characteristics that lead to uncontrolled growth and reduced immunogenicity. In the Bovine Leukemia Virus-induced ovine leukemia model, silencing of viral gene expression has been proposed as a mechanism leading to immune evasion. However, whether proviral expression in tumors is completely suppressed in vivo was not conclusively demonstrated. Therefore, we studied viral expression in two selected experimentally-infected sheep, the virus or the disease of which had features that made it possible to distinguish tumor cells from their nontransformed counterparts. Results In the first animal, we observed the emergence of a genetically modified provirus simultaneously with leukemia onset. We found a Tax-mutated (TaxK303 replication-deficient provirus in the malignant B-cell clone while functional provirus (TaxE303 had been consistently monitored over the 17-month aleukemic period. In the second case, both non-transformed and transformed BLV-infected cells were present at the same time, but at distinct sites. While there was potentially-active provirus in the non-leukemic blood B-cell population, as demonstrated by ex-vivo culture and injection into naïve sheep, virus expression was completely suppressed in the malignant B-cells isolated from the lymphoid tumors despite the absence of genetic alterations in the proviral genome. These observations suggest that silencing of viral genes, including the oncoprotein Tax, is associated with tumor onset. Conclusion Our findings suggest that silencing is critical for tumor progression and identify two distinct mechanisms-genetic and epigenetic-involved in the complete suppression of virus and Tax expression. We demonstrate that, in contrast to systems that require sustained oncogene expression, the major viral transforming protein Tax can be turned-off without reversing the transformed phenotype. We propose that suppression

  13. Elevation of blood levels of zinc protoporphyrin by radiomimetic drugs and friend leukemia virus

    International Nuclear Information System (INIS)

    Sublethal doses of whole-body irradiation induced the elevation of zinc protoporphyrin (ZPP). Experiments were conducted to determine if recovery from radiomimetic drugs also resulted in elevation of ZPP. Daily injections with hydroxyurea and other cytotoxic drugs for 10 days caused ZPP elevation and a dose of radiation too low to cause ZPP elevation by itself caused ZPP elevation when hydroxyurea was administered prior to irradiation. Friend leukemia virus also brought about an elevation of ZPP. However, not all factors that increased erythropoiesis brought about ZPP elevation. The elevated erythropoiesis in response to hypoxia and the enhanced erythropoiesis that followed administration of folic acid to folic acid-deficient mice was not accompanied by ZPP elevation. (orig.)

  14. Milk and fat yields decline in bovine leukemia virus-infected Holstein cattle with persistent lymphocytosis.

    Science.gov (United States)

    Da, Y; Shanks, R D; Stewart, J A; Lewin, H A

    1993-07-15

    Effects of bovine leukemia virus (BLV) infection on milk and fat yields were studied by using data collected from Holstein cows over a 6-year period. Milk and fat yields in BLV-infected cows with persistent lymphocytosis (PL) declined significantly relative to their BLV-infected non-PL herdmates. Declines were most pronounced in cows older than 6 years. The estimated loss to the dairy industry due to PL is more than $42 million annually. A major histocompatibility complex class I (BoLA-A) allele that has been previously associated with resistance to PL was associated with longevity and realization of milk production potentials, indicating that genetic resistance to PL will have an economic benefit in herds where BLV is endemic. PMID:8341665

  15. Fungal phosphate transporter serves as a receptor backbone for gibbon ape leukemia virus

    DEFF Research Database (Denmark)

    Pedersen, Lene; van Zeijl, Marja; Johann, Stephen V;

    1997-01-01

    Pit1, the receptor for gibbon ape leukemia virus (GALV), is proposed to be an integral membrane protein with five extracellular loops. Chimeras made between Pit1 homologs differing in permissivity for infection and between Pit1 and the related protein Pit2 have shown that the fourth extracellular...... loop plays a critical role in infection. However, further elucidation of the roles of the extracellular loops in infection is hampered by the high level of sequence similarity among these proteins. The sodium-dependent phosphate transporter, Pho-4, from the filamentous fungus Neurospora crassa is...... in a functional GALV receptor. Therefore, the presence of a Pit1 loop 4-specific sequence is sufficient to confer receptor function for the mammalian retrovirus GALV on the fungal phosphate transporter Pho-4...

  16. Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells

    International Nuclear Information System (INIS)

    Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies.

  17. Reducing the serine availability complements the inhibition of the glutamine metabolism to block leukemia cell growth

    Science.gov (United States)

    Polet, Florence; Corbet, Cyril; Pinto, Adan; Rubio, Laila Illan; Martherus, Ruben; Bol, Vanesa; Drozak, Xavier; Grégoire, Vincent; Riant, Olivier; Feron, Olivier

    2016-01-01

    Leukemia cells are described as a prototype of glucose-consuming cells with a high turnover rate. The role of glutamine in fueling the tricarboxylic acid cycle of leukemia cells was however recently identified confirming its status of major anaplerotic precursor in solid tumors. Here we examined whether glutamine metabolism could represent a therapeutic target in leukemia cells and whether resistance to this strategy could arise. We found that glutamine deprivation inhibited leukemia cell growth but also led to a glucose-independent adaptation maintaining cell survival. A proteomic study revealed that glutamine withdrawal induced the upregulation of phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase (PSAT), two enzymes of the serine pathway. We further documented that both exogenous and endogenous serine were critical for leukemia cell growth and contributed to cell regrowth following glutamine deprivation. Increase in oxidative stress upon inhibition of glutamine metabolism was identified as the trigger of the upregulation of PHGDH. Finally, we showed that PHGDH silencing in vitro and the use of serine-free diet in vivo inhibited leukemia cell growth, an effect further increased when glutamine metabolism was blocked. In conclusion, this study identified serine as a key pro-survival actor that needs to be handled to sensitize leukemia cells to glutamine-targeting modalities. PMID:26625201

  18. Seroprevalence of feline leukemia virus, feline immunodeficiency virus and heartworm infection among owned cats in tropical Mexico.

    Science.gov (United States)

    Ortega-Pacheco, Antonio; Aguilar-Caballero, Armando J; Colin-Flores, Rafael F; Acosta-Viana, Karla Y; Guzman-Marin, Eugenia; Jimenez-Coello, Matilde

    2014-06-01

    Several infectious agents may be distributed within a healthy population of cats where diverse risk factors predispose them to come into contact with pathogens. Blood samples from 227 owned cats in Merida, Mexico, were collected with the objective of determining the seroprevalence and associated risk factors of feline leukemia virus (FeLV) and Dirofilaria immitis antigen, and feline immunodeficiency virus (FIV) antibody. Serological detection of FeLV and D immitis antigens, and FIV antibodies was performed using the commercial kit SNAP Feline Triple Test. The prevalence was found to be 7.5% for FeLV, 2.5% for FIV and 0% for D immitis. Adult cats were at a higher risk of coming into contact with FeLV (P FIV. The prevalence of retroviral infections found in this study was low, but within the limits reported in the different geographical areas of the world. Cases of filariosis in the domestic cats of Merida, Mexico, may be absent or very low; however, the low sample size may have influenced these results. PMID:24196568

  19. Crystal structures of the reverse transcriptase-associated ribonuclease H domain of xenotropic murine leukemia-virus related virus

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Dongwen; Chung, Suhman; Miller, Maria; Le Grice, Stuart F.J.; Wlodawer, Alexander (NCI)

    2012-06-19

    The ribonuclease H (RNase H) domain of retroviral reverse transcriptase (RT) plays a critical role in the life cycle by degrading the RNA strands of DNA/RNA hybrids. In addition, RNase H activity is required to precisely remove the RNA primers from nascent (-) and (+) strand DNA. We report here three crystal structures of the RNase H domain of xenotropic murine leukemia virus-related virus (XMRV) RT, namely (i) the previously identified construct from which helix C was deleted, (ii) the intact domain, and (iii) the intact domain complexed with an active site {alpha}-hydroxytropolone inhibitor. Enzymatic assays showed that the intact RNase H domain retained catalytic activity, whereas the variant lacking helix C was only marginally active, corroborating the importance of this helix for enzymatic activity. Modeling of the enzyme-substrate complex elucidated the essential role of helix C in binding a DNA/RNA hybrid and its likely mode of recognition. The crystal structure of the RNase H domain complexed with {beta}-thujaplicinol clearly showed that coordination by two divalent cations mediates recognition of the inhibitor.

  20. Cell Transformation by RNA Viruses: An Overview

    OpenAIRE

    Hung Fan

    2011-01-01

    Studies of oncogenic viruses have made seminal contributions to the molecular biology of cancer. Key discoveries include the identification of viral oncogenes and cellular proto-oncogenes, elucidation of signal transduction pathways, and identification of tumor suppressor genes. The origins of cancer virology began almost exactly one hundred years ago with the discovery of avian sarcoma and acute leukemia viruses—RNA-containing viruses of the retrovirus family. The study of animal cancer viru...

  1. Identification of a feline leukemia virus variant that can use THTR1, FLVCR1, and FLVCR2 for infection.

    Science.gov (United States)

    Shalev, Zvi; Duffy, Simon P; Adema, Karen W; Prasad, Rati; Hussain, Naveen; Willett, Brian J; Tailor, Chetankumar S

    2009-07-01

    The pathogenic subgroup C feline leukemia virus (FeLV-C) arises in infected cats as a result of mutations in the envelope (Env) of the subgroup A FeLV (FeLV-A). To better understand emergence of FeLV-C and potential FeLV intermediates that may arise, we characterized FeLV Env sequences from the primary FY981 FeLV isolate previously derived from an anemic cat. Here, we report the characterization of the novel FY981 FeLV Env that is highly related to FeLV-A Env but whose variable region A (VRA) receptor recognition sequence partially resembles the VRA sequence from the prototypical FeLV-C/Sarma Env. Pseudotype viruses bearing FY981 Env were capable of infecting feline, human, and guinea pig cells, suggestive of a subgroup C phenotype, but also infected porcine ST-IOWA cells that are normally resistant to FeLV-C and to FeLV-A. Analysis of the host receptor used by FY981 suggests that FY981 can use both the FeLV-C receptor FLVCR1 and the feline FeLV-A receptor THTR1 for infection. However, our results suggest that FY981 infection of ST-IOWA cells is not mediated by the porcine homologue of FLVCR1 and THTR1 but by an alternative receptor, which we have now identified as the FLVCR1-related protein FLVCR2. Together, our results suggest that FY981 FeLV uses FLVCR1, FLVCR2, and THTR1 as receptors. Our findings suggest the possibility that pathogenic FeLV-C arises in FeLV-infected cats through intermediates that are multitropic in their receptor use. PMID:19369334

  2. Identification of a Feline Leukemia Virus Variant That Can Use THTR1, FLVCR1, and FLVCR2 for Infection▿

    Science.gov (United States)

    Shalev, Zvi; Duffy, Simon P.; Adema, Karen W.; Prasad, Rati; Hussain, Naveen; Willett, Brian J.; Tailor, Chetankumar S.

    2009-01-01

    The pathogenic subgroup C feline leukemia virus (FeLV-C) arises in infected cats as a result of mutations in the envelope (Env) of the subgroup A FeLV (FeLV-A). To better understand emergence of FeLV-C and potential FeLV intermediates that may arise, we characterized FeLV Env sequences from the primary FY981 FeLV isolate previously derived from an anemic cat. Here, we report the characterization of the novel FY981 FeLV Env that is highly related to FeLV-A Env but whose variable region A (VRA) receptor recognition sequence partially resembles the VRA sequence from the prototypical FeLV-C/Sarma Env. Pseudotype viruses bearing FY981 Env were capable of infecting feline, human, and guinea pig cells, suggestive of a subgroup C phenotype, but also infected porcine ST-IOWA cells that are normally resistant to FeLV-C and to FeLV-A. Analysis of the host receptor used by FY981 suggests that FY981 can use both the FeLV-C receptor FLVCR1 and the feline FeLV-A receptor THTR1 for infection. However, our results suggest that FY981 infection of ST-IOWA cells is not mediated by the porcine homologue of FLVCR1 and THTR1 but by an alternative receptor, which we have now identified as the FLVCR1-related protein FLVCR2. Together, our results suggest that FY981 FeLV uses FLVCR1, FLVCR2, and THTR1 as receptors. Our findings suggest the possibility that pathogenic FeLV-C arises in FeLV-infected cats through intermediates that are multitropic in their receptor use. PMID:19369334

  3. Direct polymerase chain reaction from blood and tissue samples for rapid diagnosis of bovine leukemia virus infection.

    Science.gov (United States)

    Nishimori, Asami; Konnai, Satoru; Ikebuchi, Ryoyo; Okagawa, Tomohiro; Nakahara, Ayako; Murata, Shiro; Ohashi, Kazuhiko

    2016-06-01

    Bovine leukemia virus (BLV) infection induces bovine leukemia in cattle and causes significant financial harm to farmers and farm management. There is no effective therapy or vaccine; thus, the diagnosis and elimination of BLV-infected cattle are the most effective method to eradicate the infection. Clinical veterinarians need a simpler and more rapid method of diagnosing infection, because both nested polymerase chain reaction (PCR) and real-time PCR are labor intensive, time-consuming, and require specialized molecular biology techniques and expensive equipment. In this study, we describe a novel PCR method for amplifying the BLV provirus from whole blood, thus eliminating the need for DNA extraction. Although the sensitivity of PCR directly from whole blood (PCR-DB) samples as measured in bovine blood containing BLV-infected cell lines was lower than that of nested PCR, the PCR-DB technique showed high specificity and reproducibility. Among 225 clinical samples, 49 samples were positive by nested PCR, and 37 samples were positive by PCR-DB. There were no false positive samples; thus, PCR-DB sensitivity and specificity were 75.51% and 100%, respectively. However, the provirus loads of the samples detected by nested PCR and not PCR-DB were quite low. Moreover, PCR-DB also stably amplified the BLV provirus from tumor tissue samples. PCR-DB method exhibited good reproducibility and excellent specificity and is suitable for screening of thousands of cattle, thus serving as a viable alternative to nested PCR and real-time PCR. PMID:26911373

  4. Direct polymerase chain reaction from blood and tissue samples for rapid diagnosis of bovine leukemia virus infection

    Science.gov (United States)

    NISHIMORI, Asami; KONNAI, Satoru; IKEBUCHI, Ryoyo; OKAGAWA, Tomohiro; NAKAHARA, Ayako; MURATA, Shiro; OHASHI, Kazuhiko

    2016-01-01

    Bovine leukemia virus (BLV) infection induces bovine leukemia in cattle and causes significant financial harm to farmers and farm management. There is no effective therapy or vaccine; thus, the diagnosis and elimination of BLV-infected cattle are the most effective method to eradicate the infection. Clinical veterinarians need a simpler and more rapid method of diagnosing infection, because both nested polymerase chain reaction (PCR) and real-time PCR are labor intensive, time-consuming, and require specialized molecular biology techniques and expensive equipment. In this study, we describe a novel PCR method for amplifying the BLV provirus from whole blood, thus eliminating the need for DNA extraction. Although the sensitivity of PCR directly from whole blood (PCR-DB) samples as measured in bovine blood containing BLV-infected cell lines was lower than that of nested PCR, the PCR-DB technique showed high specificity and reproducibility. Among 225 clinical samples, 49 samples were positive by nested PCR, and 37 samples were positive by PCR-DB. There were no false positive samples; thus, PCR-DB sensitivity and specificity were 75.51% and 100%, respectively. However, the provirus loads of the samples detected by nested PCR and not PCR-DB were quite low. Moreover, PCR-DB also stably amplified the BLV provirus from tumor tissue samples. PCR-DB method exhibited good reproducibility and excellent specificity and is suitable for screening of thousands of cattle, thus serving as a viable alternative to nested PCR and real-time PCR. PMID:26911373

  5. Prognostic significance of cell surface phenotype in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Shiek Aejaz Aziz

    2015-01-01

    Full Text Available Context: To find out the phenotypic character of lymphoblasts of acute lymphoblastic leukemia (ALL patients in our study cohort and their possible effect on the prognosis. Aims: To investigate the phenotype in ALL in our demographic population and to prognosticate various upfront current protocols employed in our hospital. Settings and Design: The study spanned over a period of 4 years with retrospective and prospective data of January 2008 through December 2011. Materials and Methods: 159 patients of all age groups were enrolled for the study, of which flow cytometry was done in 144 patients. Statistical Analysis Used: Analysis was done using the variables on SPSS (statistical package for social sciences software on computer. Survival curves were estimated by method of Kaplan-Meir. Results: Majority of the patients were of B-cell (68.1% and 30.6% patients were of T-cell lineage. Of these, 80.6% patients were having cALLa positivity. Complete remission (CR was achieved in 59.1%, 16.4% relapsed, and 20.1% patients died. Conclusions: Phenotyping has become an important and integral part of diagnosis, classification, management and prognosticating in ALL. B-cell has been found to have a better survival over T-cell lymphoblastic leukemia. cALLa antigen positivity has good impact in achieving CR in only B-cell lineage, myeloid coexpression has no significant effect on the outcome. BFM (Berlin-Frankfurt-Münster based protocols though showed a higher CR and survival vis-a-vis UKALL-XII. However, patients enrolled in former group being of low risk category and lesser in numbers cannot be compared statistically with a fair degree of confidence.

  6. High prevalence of Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) in Slovenia

    OpenAIRE

    Tozon Nataša; Svete Nemec A.; Zemljič M.; Zakošek M.; Barlič-Maganja Darja

    2008-01-01

    The purpose of this study was to determine the prevalences of FIV and FeLV infections in domestic cats by the enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). Of the 42 cats examined by the ELISA test, 14 (33.3 %) were seropositive for FIV antibody, 10 (23.8 %) for FeLV antigen, 1 (2.4 %) was positive for both viruses and 17 were negative for infection with either virus. In the PCR assay, 17 cats (40.5 %) were positive for FeLV, 11 (26.2%) for FIV, 9 (21.4%) for ...

  7. L233P mutation of the Tax protein strongly correlated with leukemogenicity of bovine leukemia virus.

    Science.gov (United States)

    Inoue, Emi; Matsumura, Keiko; Soma, Norihiko; Hirasawa, Shintaro; Wakimoto, Mayuko; Arakaki, Yoshihiro; Yoshida, Takashi; Osawa, Yoshiaki; Okazaki, Katsunori

    2013-12-27

    The bovine leukemia virus (BLV) Tax protein is believed to play a crucial role in leukemogenesis by the virus. BLV usually causes asymptomatic infections in cattle, but only one-third develop persistent lymphocytosis that rarely progress after a long incubation period to lymphoid tumors, namely enzootic bovine leucosis (EBL). In the present study, we demonstrated that the BLV tax genes could be divided into two alleles and developed multiplex PCR detecting an L233P mutation of the Tax protein. Then, in order to define the relationship between the Tax protein and leukemogenicity, we examined 360 tumor samples randomly collected from dairy or breeding cattle in Japan, of which Tax proteins were categorized, for age at the time of diagnosis of EBL. The ages of 288 animals (80.0%) associated with L233-Tax and those of 70 animals (19.4%) with P233-Tax individually followed log-normal distributions. Only the two earliest cases (0.6%) with L233-Tax disobeyed the log-normal distribution. These findings suggest that the animals affected by EBL were infected with the virus at a particular point in life, probably less than a few months after birth. Median age of those with P233-Tax was 22 months older than that with L233-Tax and geometric means exhibited a significant difference (P<0.01). It is also quite unlikely that viruses carrying the particular Tax protein infect older cattle. Here, we conclude that BLV could be divided into two categories on the basis of amino acid at position 233 of the Tax protein, which strongly correlated with leukemogenicity. PMID:24139177

  8. Friend leukemia virus integration 1 activates the Rho GTPase pathway and is associated with metastasis in breast cancer.

    Science.gov (United States)

    Song, Wei; Li, Wei; Li, Lingyu; Zhang, Shilin; Yan, Xu; Wen, Xue; Zhang, Xiaoying; Tian, Huimin; Li, Ailing; Hu, Ji-Fan; Cui, Jiuwei

    2015-09-15

    Breast cancer is the most prevalent malignant disease in women worldwide. In patients with breast cancer, metastasis to distant sites directly determines the survival outcome. However, the molecular mechanism underlying metastasis in breast cancer remains to be defined. In this report, we found that Friend leukemia virus integration 1 (FLI1) proto-oncogene was differentially expressed between the aggressive MDA-MB231 and the non-aggressive MCF-7 breast cancer cells. Congruently, immunohistochemical staining of clinical samples revealed that FLI1 was overexpressed in breast cancers as compared with the adjacent tissues. The abundance of FLI1 protein was strongly correlated with the advanced stage, poor differentiation, and lymph node metastasis in breast cancer patients. Knockdown of FLI1 with small interfering RNAs significantly attenuated the potential of migration and invasion in highly metastatic human breast cancer cells. FLI1 oncoprotein activated the Rho GTPase pathway that is known to play a role in tumor metastasis. This study for the first time identifies FLI1 as a clinically and functionally important target gene of metastasis, providing a rationale for developing FLI1 inhibitors in the treatment of breast cancer. PMID:26156017

  9. Retinoic acid. Inhibition of the clonal growth of human myeloid leukemia cells.

    OpenAIRE

    Douer, D; Koeffler, H P

    1982-01-01

    Vitamin A and its analogues (retinoids) affect normal and malignant hematopoietic cells. We examined the effect of retinoids on the clonal growth in vitro of myeloid leukemia cells. Retinoic acid inhibited the clonal growth of the KG-1, acute myeloblastic leukemia, and the HL-60, acute promyelocytic leukemia, human cell lines. The KG-1 cells were extremely sensitive to retinoic acid, with 50% of the colonies inhibited by 2.4-nM concentrations of the drug. A 50% growth inhibition of HL-60 was ...

  10. Aptamer-Functionalized Fluorescent Silica Nanoparticles for Highly Sensitive Detection of Leukemia Cells

    Science.gov (United States)

    Tan, Juntao; Yang, Nuo; Hu, Zixi; Su, Jing; Zhong, Jianhong; Yang, Yang; Yu, Yating; Zhu, Jianmeng; Xue, Dabin; Huang, Yingying; Lai, Zongqiang; Huang, Yong; Lu, Xiaoling; Zhao, Yongxiang

    2016-06-01

    A simple, highly sensitive method to detect leukemia cells has been developed based on aptamer-modified fluorescent silica nanoparticles (FSNPs). In this strategy, the amine-labeled Sgc8 aptamer was conjugated to carboxyl-modified FSNPs via amide coupling between amino and carboxyl groups. Sensitivity and specificity of Sgc8-FSNPs were assessed using flow cytometry and fluorescence microscopy. These results showed that Sgc8-FSNPs detected leukemia cells with high sensitivity and specificity. Aptamer-modified FSNPs hold promise for sensitive and specific detection of leukemia cells. Changing the aptamer may allow the FSNPs to detect other types of cancer cells.

  11. Aptamer-Functionalized Fluorescent Silica Nanoparticles for Highly Sensitive Detection of Leukemia Cells.

    Science.gov (United States)

    Tan, Juntao; Yang, Nuo; Hu, Zixi; Su, Jing; Zhong, Jianhong; Yang, Yang; Yu, Yating; Zhu, Jianmeng; Xue, Dabin; Huang, Yingying; Lai, Zongqiang; Huang, Yong; Lu, Xiaoling; Zhao, Yongxiang

    2016-12-01

    A simple, highly sensitive method to detect leukemia cells has been developed based on aptamer-modified fluorescent silica nanoparticles (FSNPs). In this strategy, the amine-labeled Sgc8 aptamer was conjugated to carboxyl-modified FSNPs via amide coupling between amino and carboxyl groups. Sensitivity and specificity of Sgc8-FSNPs were assessed using flow cytometry and fluorescence microscopy. These results showed that Sgc8-FSNPs detected leukemia cells with high sensitivity and specificity. Aptamer-modified FSNPs hold promise for sensitive and specific detection of leukemia cells. Changing the aptamer may allow the FSNPs to detect other types of cancer cells. PMID:27299653

  12. Prolonged treatment response in aggressive natural killer cell leukemia.

    Science.gov (United States)

    Osuji, N; Matutes, E; Morilla, A; Del Giudice, I; Wotherspoon, A; Catovsky, D

    2005-05-01

    We describe a case of natural killer (NK) cell leukemia with acute presentation, systemic symptoms and hepatosplenomegaly. The uniform and aberrant phenotype of NK cells with infiltration of bone marrow and spleen was in keeping with a malignant diagnosis. Aggressive presentation was demonstrated by marked constitutional symptoms and significant tumor burden (liver, spleen, blood, bone marrow). The subsequent clinical course has been indolent, but this may have been influenced by treatment. Treatment consisted sequentially of splenectomy, intravenous pentostatin and the combination of cyclosporine A and recombinant human erythropoietin and has resulted in survival of over 48 months. We discuss the difficulties in the diagnosis of this condition, explore possible causes of cytopenia(s), and highlight the role of immunosuppression in controlling disease manifestations in large granular lymphocyte proliferative disorders. PMID:16019515

  13. A rare case of plasma cell leukemia in a 35 year old

    OpenAIRE

    Dosi, Rupal V; Annirudh Ambaliya; Patell, Rushad D.; Harshal J Joshi

    2010-01-01

    Plasma cell leukemia is a rare, aggressive form of multiple myeloma. A 35-year-old male presented with backache, generalized weakness, and facial puffiness. His complete blood count showed anemia and a high WBC count with atypical cells on peripheral smear. Bone marrow examination showed more than 90% of atypical plasma cells, confirming a diagnosis of plasma cell leukemia. Patient also had azotemia, hypercalcemia, and hyperuricemia. The patient was started on chemotherapy along with supporti...

  14. Distinctive receptor binding properties of the surface glycoprotein of a natural Feline Leukemia Virus isolate with unusual disease spectrum

    Directory of Open Access Journals (Sweden)

    Albritton Lorraine M

    2011-05-01

    Full Text Available Abstract Background Feline leukemia virus (FeLV-945, a member of the FeLV-A subgroup, was previously isolated from a cohort of naturally infected cats. An unusual multicentric lymphoma of non-T-cell origin was observed in natural and experimental infection with FeLV-945. Previous studies implicated the FeLV-945 surface glycoprotein (SU as a determinant of disease outcome by an as yet unknown mechanism. The present studies demonstrate that FeLV-945 SU confers distinctive properties of binding to the cell surface receptor. Results Virions bearing the FeLV-945 Env protein were observed to bind the cell surface receptor with significantly increased efficiency, as was soluble FeLV-945 SU protein, as compared to the corresponding virions or soluble protein from a prototype FeLV-A isolate. SU proteins cloned from other cohort isolates exhibited increased binding efficiency comparable to or greater than FeLV-945 SU. Mutational analysis implicated a domain containing variable region B (VRB to be the major determinant of increased receptor binding, and identified a single residue, valine 186, to be responsible for the effect. Conclusions The FeLV-945 SU protein binds its cell surface receptor, feTHTR1, with significantly greater efficiency than does that of prototype FeLV-A (FeLV-A/61E when present on the surface of virus particles or in soluble form, demonstrating a 2-fold difference in the relative dissociation constant. The results implicate a single residue, valine 186, as the major determinant of increased binding affinity. Computational modeling suggests a molecular mechanism by which residue 186 interacts with the receptor-binding domain through residue glutamine 110 to effect increased binding affinity. Through its increased receptor binding affinity, FeLV-945 SU might function in pathogenesis by increasing the rate of virus entry and spread in vivo, or by facilitating entry into a novel target cell with a low receptor density.

  15. A Good Manufacturing Practice procedure to engineer donor virus-specific T cells into potent anti-leukemic effector cells.

    Science.gov (United States)

    van Loenen, Marleen M; de Boer, Renate; van Liempt, Ellis; Meij, Pauline; Jedema, Inge; Falkenburg, J H Frederik; Heemskerk, Mirjam H M

    2014-04-01

    A sequential, two-step procedure in which T-cell-depleted allogeneic stem cell transplantation is followed by treatment with donor lymphocyte infusion at 6 months can significantly reduce the risk and severity of graft-versus-host disease, with postponed induction of the beneficial graft-versus-leukemia effect. However, patients with high-risk leukemia have a substantial risk of relapse early after transplantation, at a time when administration of donor lymphocytes has a high likelihood of resulting in graft-versus-host disease, disturbing a favorable balance between the graft-versus-leukemia effect and graft-versus-host disease. New therapeutic modalities are, therefore, required to allow early administration of T cells capable of exerting a graft-versus-leukemia effect without causing graft-versus-host disease. Here we describe the isolation of virus-specific T cells using Streptamer-based isolation technology and subsequent transfer of the minor histocompatibility antigen HA-1-specific T-cell receptor using retroviral vectors. Isolation of virus-specific T cells and subsequent transduction with HA-1-T-cell receptor resulted in rapid in vitro generation of highly pure, dual-specific T cells with potent anti-leukemic reactivity. Due to the short production procedure of only 10-14 days and the defined specificity of the T cells, administration of virus-specific T cells transduced with the HA-1-T-cell receptor as early as 8 weeks after allogeneic stem cell transplantation is feasible. (This clinical trial is registered at www.clinicaltrialsregister.eu as EudraCT number 2010-024625-20). PMID:24334296

  16. 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

  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. Current and emerging treatment options for hairy cell leukemia

    Directory of Open Access Journals (Sweden)

    López-Rubio M

    2015-08-01

    Full Text Available Montserrat López-Rubio,1 Jose Antonio Garcia-Marco2 1Department of Hematology, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, 2Department of Hematology, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Spain Abstract: Hairy cell leukemia (HCL is a lymphoproliferative B-cell disorder characterized by pancytopenia, splenomegaly, and characteristic cytoplasmic hairy projections. Precise diagnosis is essential in order to differentiate classic forms from HCL variants, such as the HCL-variant and VH4-34 molecular variant, which are more resistant to available treatments. The current standard of care is treatment with purine analogs (PAs, such as cladribine or pentostatin, which provide a high rate of long-lasting clinical remissions. Nevertheless, ~30%–40% of the patients relapse, and moreover, some of these are difficult-to-treat refractory cases. The use of the monoclonal antibody rituximab in combination with PA appears to produce even higher responses, and it is often employed to minimize or eliminate residual disease. Currently, research in the field of HCL is focused on identifying novel therapeutic targets and potential agents that are safe and can universally cure the disease. The discovery of the BRAF mutation and progress in understanding the biology of the disease has enabled the scientific community to explore new therapeutic targets. Ongoing clinical trials are assessing various treatment strategies such as the combination of PA and anti-CD20 monoclonal antibodies, recombinant immunotoxins targeting CD22, BRAF inhibitors, and B-cell receptor signal inhibitors. Keywords: hairy cell leukemia, purine analogs, rituximab, immunotoxins, vemurafenib, ibrutinib

  19. Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia in Adults.

    Science.gov (United States)

    Speziali, Craig; Paulson, Kristjan; Seftel, Matthew

    2016-06-01

    The majority of adults with acute lymphoblastic leukemia will achieve a first complete remission (CR). However relapse is the most common cause of treatment failure. Outcomes after relapse remain poor, with long-term survival in the order of 10 %. Treatment decisions made at the time of first complete remission are thus critical to ensuring long-term survival. Allogeneic hematopoietic cell transplant (HCT) is effective at preventing relapse in many transplant recipients but is also associated with significant treatment related morbidity and mortality. Alternatively, ongoing systemic chemotherapy offers lower toxicity at the expense of increased relapse rates. Over the past decades, both the safety of transplant and the efficacy of non-transplant chemotherapy have improved. Emerging data show substantially improved outcomes for young adults treated with pediatric-inspired chemotherapy regimens that question the role of HCT in the upfront setting. In this review, we review the data supporting the role of allogeneic transplantation in adult acute lymphoblastic leukemia (ALL), and we propose a therapeutic algorithm for upfront therapy of adults with ALL. PMID:26984203

  20. 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)

  1. Adult T-cell lymphoma/leukemia presenting as isolated central nervous system T-cell lymphoma.

    Science.gov (United States)

    Ma, Wei-Li; Li, Chi-Cheng; Yu, Shan-Chi; Tien, Hwei-Fang

    2014-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a T-cell neoplasm, associated with infection by the retrovirus human T-lymphotropic virus type 1 (HTLV-1). Central nervous system (CNS) involved by ATLL is often occurred in advanced disease, such as acute and lymphomatous variants. On the other hand, isolated CNS lymphoma is rare. We repot a 50-year-old woman who presented with multiple infiltrative brain lesions on the magnetic resonance (MR) imaging. Results of initial biopsy of brain tumor indicated CNS vasculitis. The patient received one course of high-dose methotrexate and MR imaging of brain revealed remission of infiltrative lesions. Two years later, new brain lesions were detected. Histopathologic examination of specimens via craniotomy revealed T-cell lymphoma. The patient responded poorly to subsequent chemotherapy, and salvage whole-brain irradiation was performed. Six months later, the patient had hepatosplenomegaly, hypercalcemia, and multiple lymphocytes with a cloverleaf appearance in circulation. Results of flow cytometry analysis of peripheral blood indicated ATLL and antibodies to human T-lymphotropic virus type 1 (HTLV-1) were detected. Clinicians should screen HTLV-1 infection when patients are diagnosed with peripheral T-cell lymphoma. Combined antiviral therapy and intensive chemotherapy may improve the outcomes of ATLL. PMID:25587470

  2. Adult T-Cell Lymphoma/Leukemia Presenting as Isolated Central Nervous System T-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Wei-Li Ma

    2014-01-01

    Full Text Available Adult T-cell leukemia/lymphoma (ATLL is a T-cell neoplasm, associated with infection by the retrovirus human T-lymphotropic virus type 1 (HTLV-1. Central nervous system (CNS involved by ATLL is often occurred in advanced disease, such as acute and lymphomatous variants. On the other hand, isolated CNS lymphoma is rare. We repot a 50-year-old woman who presented with multiple infiltrative brain lesions on the magnetic resonance (MR imaging. Results of initial biopsy of brain tumor indicated CNS vasculitis. The patient received one course of high-dose methotrexate and MR imaging of brain revealed remission of infiltrative lesions. Two years later, new brain lesions were detected. Histopathologic examination of specimens via craniotomy revealed T-cell lymphoma. The patient responded poorly to subsequent chemotherapy, and salvage whole-brain irradiation was performed. Six months later, the patient had hepatosplenomegaly, hypercalcemia, and multiple lymphocytes with a cloverleaf appearance in circulation. Results of flow cytometry analysis of peripheral blood indicated ATLL and antibodies to human T-lymphotropic virus type 1 (HTLV-1 were detected. Clinicians should screen HTLV-1 infection when patients are diagnosed with peripheral T-cell lymphoma. Combined antiviral therapy and intensive chemotherapy may improve the outcomes of ATLL.

  3. Differential multimerization of Moloney murine leukemia virus integrase purified under nondenaturing conditions

    International Nuclear Information System (INIS)

    Retroviral integrases (IN) catalyze the integration of the reverse-transcribed viral DNA into the host genome, an essential process leading to virus replication. For Moloney murine leukemia virus (M-MuLV) IN, the limited solubility of the recombinant protein has restricted the development of biophysical and structural analyses. Herein, recombinant M-MuLV IN proteins, either full length or two nonoverlapping domain constructs, were purified under non-denaturing conditions from solubilized bacterial extracts by Ni2+-NTA resins. Additionally, WT IN was further purified by heparin chromatography. All of the purified proteins were shown to be active and stable. WT M-MuLV IN chromatographed with a peak corresponding with a dimer by gel filtration chromatography. In contrast, the single point mutant C209A IN migrated predominantly as a tetramer. For both proteins, fractions in equilibrium between dimers and tetramers were competent to assemble concerted two-end integrations and yielded a unique strand-transfer profile in the presence of a 28-mer U5 oligonucleotide substrate, indicative of a distinct conformation within the synaptic complex. This specific target-site selection was not observed with a shorter 20-mer U5 substrate. These studies provide the foundation for biophysical and structural analysis on M-MuLV IN and the mechanism of retroviral integration

  4. Murine leukemia virus in organs of senescence-prone and -resistant mouse strains.

    Science.gov (United States)

    Carp, R I; Meeker, H C; Chung, R; Kozak, C A; Hosokawa, M; Fujisawa, H

    2002-03-31

    A series of inbred strains of mice have been developed that are either prone (SAMP) or resistant (SAMR) to accelerated senescence. All of these strains originated from an inadvertent cross or crosses between the AKR/J mouse strain and an unknown strain(s). The characteristics of the nine senescence-prone lines differ, with all strains showing generalized aspects of accelerated aging but with each line having a specific aging-related change that is emphasized, e.g. learning and memory deficits, osteoporosis and senile amyloidosis. The senescence-resistant strains have normal patterns of aging and do not show the specific aging-related changes seen in SAMP strains. The fact that AKR mice have high levels of endogenous, ecotropic murine leukemia virus (MuLV) prompted an examination of the expression levels of MuLV in SAM strains. Analysis of brain, spleen and thymus samples revealed that seven of nine SAMP strains had high levels of MuLV and contained the Emv11 provirus (previously termed Akv1) that encodes the predominant MuLV found in AKR mice. In contrast, none of the SAMR strains had Emv11 or significant amounts of virus. The current findings represent an initial step in determining the role of MuLV in the accelerated senescence seen in SAMP strains. PMID:11850021

  5. Leukemia cutis

    Directory of Open Access Journals (Sweden)

    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. Evaluating enzootic bovine leukemia virus infection by means of molecular probe compared with the results of serological tests

    International Nuclear Information System (INIS)

    The present studies were aimed at determining the relation between the finding obtained by means of serological tests and the specific molecular probe. Serological tests were performed according to the methods recommended by the Polish Ministry of Agriculture; ELISA was run with ''Bioveta'' and ''Rhone Merieux'' kits and the AGID test was performed with EBL antigen made in our laboratory. The molecular probe was prepared from the previously cloned provirus DNA of EBL virus. The EBL provirus was detected in 28 samples taken from 44 randomly selected cows in three herds on which a leukemia eradication programme was in process. Three sera out of 28 positive reacting animals were negative in AGID test and only one serum in ELISA. The results indicate that the use of a specific molecular probe has some advantages in the diagnosis of latent virus infections. Besides, it can be applied in the studies on the pathogenesis of enzootic bovine leukemia. (author). 13 refs, 1 fig., 1 tab

  7. Establishment and genetic characterization of a novel mixed-phenotype acute leukemia cell line with EP300-ZNF384 fusion

    OpenAIRE

    Ping, Nana; Qiu, Huiying; Wang, Qian; Dai, Haiping; Ruan, Changgeng; Ehrentraut, Stefan; Drexler, Hans G.; MacLeod, Roderick A. F.; Chen, Suning

    2015-01-01

    Herein, we describe the establishment and characterization of the first mixed-phenotype acute leukemia cell line (JIH-5). The JIH-5 cell line was established from leukemia cells with B lymphoid/myeloid phenotype from a female mixed-phenotype acute leukemia patient. JIH-5 cells exhibit an immunophenotype comprised of myeloid and B lymphoid antigens. Whole-exome sequencing revealed somatic mutations in nine genes in JIH-5 cells. Transcriptional sequencing of JIH-5 cells identified EP300-ZNF384 ...

  8. High prevalence of Feline Immunodeficiency Virus (FIV and Feline Leukemia Virus (FeLV in Slovenia

    Directory of Open Access Journals (Sweden)

    Tozon Nataša

    2008-01-01

    Full Text Available The purpose of this study was to determine the prevalences of FIV and FeLV infections in domestic cats by the enzyme-linked immunosorbent assay (ELISA and polymerase chain reaction (PCR. Of the 42 cats examined by the ELISA test, 14 (33.3 % were seropositive for FIV antibody, 10 (23.8 % for FeLV antigen, 1 (2.4 % was positive for both viruses and 17 were negative for infection with either virus. In the PCR assay, 17 cats (40.5 % were positive for FeLV, 11 (26.2% for FIV, 9 (21.4% for both viruses and 5 cats (11.9% were negative for the presence of viral DNA. The average age of FIV positive cats was 6 and of FeLV 7 years. Infections were more common in outdoor cats (65% FIV, 61.1% FeLV positive and in male cats (71.4% FIV, 80% FeLV. The results of both tests used in this study have shown high prevalence of both infections among cats in Slovenia. The ELISA method was found useful as a screening test for fast detection of FIV and FeLV infections, but additional testing with PCR was shown to be more effective in the characterization and progression of both infections.

  9. Prognostic relevance of RUNX1 mutations in T-cell acute lymphoblastic leukemia

    OpenAIRE

    Grossmann, Vera; Kern, Wolfgang; Harbich, Stefan; Alpermann, Tamara; Jeromin, Sabine; Schnittger, Susanne; Haferlach, Claudia; Haferlach, Torsten; Kohlmann, Alexander

    2011-01-01

    The runt-related transcription factor 1, RUNX1, is crucial in the development of myeloid and lymphoid cell lineages and has been reported to be mutated in myeloid malignancies in approximately 30% of cases. In this study, the mutational status of RUNX1 was investigated in 128 acute lymphoblastic leukemia patients. We detected a mutation rate of 18.3% (13 of 71) in patients with T-cell acute lymphoblastic leukemia, 3.8% (2 of 52) in patients with B-cell acute lymphoblastic leukemia and no muta...

  10. Acute myelogenous leukemia cells with the MLL-ELL translocation convert morphologically and functionally into adherent myofibroblasts

    International Nuclear Information System (INIS)

    Bone marrow-myofibroblasts, a major component of bone marrow-stroma, are reported to originate from hematopoietic stem cells. We show in this paper that non-adherent leukemia blasts can change into myofibroblasts. When myeloblasts from two cases of acute myelogenous leukemia with a fusion product comprising mixed lineage leukemia and RNA polymerase II elongation factor, were cultured long term, their morphology changed to that of myofibroblasts with similar molecular characteristics to the parental myeloblasts. The original leukemia blasts, when cultured on the leukemia blast-derived myofibroblasts, grew extensively. Leukemia blasts can create their own microenvironment for proliferation.

  11. Receptor-Triggered but Alkylation-Arrested Env of Murine Leukemia Virus Reveals the Transmembrane Subunit in a Prehairpin Conformation

    OpenAIRE

    Wallin, Michael; Ekström, Maria; Garoff, Henrik

    2006-01-01

    A central feature of the prevailing model for retrovirus fusion is conversion of the transmembrane (TM) subunit from a prehairpin to a hairpin-like structure. The fusion inhibition of many retroviruses, except murine leukemia virus (MLV), with peptides corresponding to interacting regions in the hairpin supports the model. MLV fusion is controlled by isomerization of the intersubunit disulfide in Env. We show here that TM peptides bind to MLV Env that has been arrested at an intermediate stag...

  12. Effects of Limiting Homology at the Site of Intermolecular Recombinogenic Template Switching during Moloney Murine Leukemia Virus Replication

    OpenAIRE

    Pfeiffer, Julie K.; Telesnitsky, Alice

    2001-01-01

    A Moloney murine leukemia virus-based single-replication-cycle assay was developed to study the effects of limiting the extent of template and primer strand complementarity on recombinogenic template switching. This system mimicked forced copy choice recombination in which nascent DNA transfers from the end of a donor template to an acceptor position on the other copackaged RNA. When acceptor target regions with different extents of complementarity to the transferring DNA were tested, efficie...

  13. Application of a sepharose bead immunofluorescence assay and a solid-phase radioimmunoassay to the bovine leukemia virus system

    International Nuclear Information System (INIS)

    Several fluorescence assays with bovine leukemia virus (BLV) conjugated to activated Sepharose 4B were used for the detection of BLV and anti-BLV antibodies. These tests were compared with a solid-phase radioimmunoassay and found to be in the same sensitivity range. Sepharose bead immunofluorescence assay and solid-phase radioimmunoassay can be applied to the diagnosis of BLV infection in cattle. (author)

  14. Using a Herd Profile to Determine Age-Specific Prevalence of Bovine Leukemia Virus in Michigan Dairy Herds

    OpenAIRE

    Catherine Febvay; Chelsea L. Render; Byrem, Todd M.; Bartlett, Paul C.; Erskine, Ronald J.; Jessica T. Houseman

    2012-01-01

    Enzootic bovine leukosis is a contagious disease of cattle caused by the retrovirus, bovine leukemia virus (BLV) and is the most common cause of malignant neoplasm in cattle. In order to facilitate surveillance of this disease in dairy herds, we developed a method to combine ELISA of milk collected during routine production testing with a prescribed sampling of cows that is independent of the proportion of cows within each lactation. In 113 Michigan dairy herds, milk samples from ten cows in ...

  15. Risk factors associated with within-herd transmission of bovine leukemia virus on dairy farms in Japan

    OpenAIRE

    Konishi Misako; Kameyama Ken-ichiro; Hayama Yoko; Yamamoto Takehisa; Tsutsui Toshiyuki; Kobayashi Sota; Murakami Kenji

    2010-01-01

    Abstract Background Although several attempts have been made to control enzootic bovine leukosis (EBL) at the local level, a nationwide control program has not been implemented in Japan, except for passive surveillance. Effective control of EBL requires that the transmission routes of bovine leukemia virus (BLV) infection should be identified and intercepted based on scientific evidence. In this cross-sectional study, we examined the risk factors associated with within-herd transmission of BL...

  16. Iron and Ferritin Levels in the Serum and Milk of Bovine Leukemia Virus-Infected Dairy Cows

    OpenAIRE

    Schnell, Star A.; Ohtsuka, Hiromichi; Kakinuma, Seiichi; Yoshikawa, Yasunaga; Watanabe, Kiyotaka; Orino, Koichi

    2015-01-01

    Iron metabolism was examined in 15 bovine leukemia virus (BLV)-infected dairy cows (2.6–7.8 years old). BLV infection was detected by measuring serum antibody titer against BLV virus antigen (gp51). The anti-BLV antibody titers of the BLV-infected cows were significantly higher in serum than in milk; a single serum-positive animal lacked detectable anti-BLV antibodies in its milk. Iron and ferritin concentrations also were significantly higher in serum than in milk. Although most of the BLV-i...

  17. 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.

  18. Flow cytometric and radioisotopic determinations of platelet survival time in normal cats and feline leukemia virus-infected cats

    International Nuclear Information System (INIS)

    This study demonstrates the potential usefulness of a flow cytometric technique to measure platelet survival time in cats utilizing autologous platelets labeled in vitro with fluorescein isothiocyanate (FITC). When compared with a 51Cr method, no significant differences in estimated survival times were found. Both the 51Cr and FITC-labeling procedures induced similar changes in platelet shape and collagen-induced aggregation. Platelets labeled with FITC had significantly greater volumes compared with those of glutaraldehyde-fixed platelets. These changes were primarily related to the platelet centrifugation and washing procedures rather than the labels themselves. This novel technique potentially has wide applicability to cell circulation time studies as flow cytometry equipment becomes more readily available. Problems with the technique are discussed. In a preliminary study of the platelet survival time in feline leukemia virus (FeLV)-infected cats, two of three cats had significantly reduced survival times using both flow cytometric and radioisotopic methods. These data suggest increased platelet turnover in FeLV-infected cats

  19. Epstein-Barr virus DNA load in chronic lymphocytic leukemia is an independent predictor of clinical course and survival.

    Science.gov (United States)

    Visco, Carlo; Falisi, Erika; Young, Ken H; Pascarella, Michela; Perbellini, Omar; Carli, Giuseppe; Novella, Elisabetta; Rossi, Davide; Giaretta, Ilaria; Cavallini, Chiara; Scupoli, Maria Teresa; De Rossi, Anita; D'Amore, Emanuele Stefano Giovanni; Rassu, Mario; Gaidano, Gianluca; Pizzolo, Giovanni; Ambrosetti, Achille; Rodeghiero, Francesco

    2015-07-30

    The relation between Epstein-Barr virus (EBV) DNA load and clinical course of patients with chronic lymphocytic leukemia (CLL) is unknown. We assessed EBV DNA load by quantitative PCR at CLL presentation in mononuclear cells (MNC) of 220 prospective patients that were enrolled and followed-up in two major Institutions. In 20 patients EBV DNA load was also assessed on plasma samples. Forty-one age-matched healthy subjects were tested for EBV DNA load on MNC. Findings were validated in an independent retrospective cohort of 112 patients with CLL. EBV DNA load was detectable in 59%, and high (≥2000 copies/µg DNA) in 19% of patients, but it was negative in plasma samples. EBV DNA load was significantly higher in CLL patients than in healthy subjects (P variables, except for 11q deletion (P = .004), CD38 expression (P = .003), and NOTCH1 mutations (P = .05). High EBV load led to a 3.14-fold increase in the hazard ratio of death and to a shorter overall survival (OS; P = .001). Poor OS was attributable, at least in part, to shorter time-to-first-treatment (P = .0008), with no higher risk of Richter's transformation or second cancer. Multivariate analysis selected high levels of EBV load as independent predictor of OS after controlling for confounding clinical and biological variables. EBV DNA load at presentation is an independent predictor of OS in patients with CLL. PMID:26087198

  20. Maintenance of leukemia-initiating cells is regulated by the CDK inhibitor Inca1.

    Directory of Open Access Journals (Sweden)

    Nicole Bäumer

    Full Text Available Functional differences between healthy progenitor and cancer initiating cells may provide unique opportunities for targeted therapy approaches. Hematopoietic stem cells are tightly controlled by a network of CDK inhibitors that govern proliferation and prevent stem cell exhaustion. Loss of Inca1 led to an increased number of short-term hematopoietic stem cells in older mice, but Inca1 seems largely dispensable for normal hematopoiesis. On the other hand, Inca1-deficiency enhanced cell cycling upon cytotoxic stress and accelerated bone marrow exhaustion. Moreover, AML1-ETO9a-induced proliferation was not sustained in Inca1-deficient cells in vivo. As a consequence, leukemia induction and leukemia maintenance were severely impaired in Inca1-/- bone marrow cells. The re-initiation of leukemia was also significantly inhibited in absence of Inca1-/- in MLL-AF9- and c-myc/BCL2-positive leukemia mouse models. These findings indicate distinct functional properties of Inca1 in normal hematopoietic cells compared to leukemia initiating cells. Such functional differences might be used to design specific therapy approaches in leukemia.

  1. Bone marrow niche-mediated survival of leukemia stem cells in acute myeloid leukemia: Yin and Yang

    Science.gov (United States)

    Zhou, Hong-Sheng; Carter, Bing Z.; Andreeff, Michael

    2016-01-01

    Acute myeloid leukemia (AML) is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity to apoptosis. Accumulating evidence shows the bone marrow (BM) niche is critical to the maintenance and retention of hematopoietic stem cells (HSC), including leukemia stem cells (LSC), and an increasing number of studies have demonstrated that crosstalk between LSC and the stromal cells associated with this niche greatly influences leukemia initiation, progression, and response to therapy. Undeniably, stromal cells in the BM niche provide a sanctuary in which LSC can acquire a drug-resistant phenotype and thereby evade chemotherapy-induced death. Yin and Yang, the ancient Chinese philosophical concept, vividly portrays the intricate and dynamic interactions between LSC and the BM niche. In fact, LSC-induced microenvironmental reprogramming contributes significantly to leukemogenesis. Thus, identifying the critical signaling pathways involved in these interactions will contribute to target optimization and combinatorial drug treatment strategies to overcome acquired drug resistance and prevent relapse following therapy. In this review, we describe some of the critical signaling pathways mediating BM niche-LSC interaction, including SDF1/CXCL12, Wnt/β-catenin, VCAM/VLA-4/NF-κB, CD44, and hypoxia as a newly-recognized physical determinant of resistance, and outline therapeutic strategies for overcoming these resistance factors.

  2. Ayanin diacetate-induced cell death is amplified by TRAIL in human leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Marrero, Maria Teresa; Estevez, Sara; Negrin, Gledy; Quintana, Jose [Departamento de Bioquimica, Unidad Asociada al Consejo Superior de Investigaciones Cientificas, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria (Spain); Lopez, Mariana; Perez, Francisco J.; Triana, Jorge [Departamento de Quimica, Universidad de Las Palmas de Gran Canaria, Instituto Canario de Investigacion del Cancer, 35017 Las Palmas de Gran Canaria (Spain); Leon, Francisco [Instituto de Productos Naturales y Agrobiologia, Consejo Superior de Investigaciones Cientificas, Avda. Astrofisico F. Sanchez 3, 38206 La Laguna, Tenerife (Spain); Estevez, Francisco, E-mail: festevez@dbbf.ulpgc.es [Departamento de Bioquimica, Unidad Asociada al Consejo Superior de Investigaciones Cientificas, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria (Spain)

    2012-11-09

    Highlights: Black-Right-Pointing-Pointer Ayanin diacetate as apoptotic inducer in leukemia cells. Black-Right-Pointing-Pointer Cell death was prevented by caspase inhibitors and by the overexpression of Bcl-x{sub L}. Black-Right-Pointing-Pointer The intrinsic and the extrinsic pathways are involved in the mechanism of action. Black-Right-Pointing-Pointer Death receptors are up-regulated and TRAIL enhances apoptotic cell death. -- Abstract: Here we demonstrate that the semi-synthetic flavonoid ayanin diacetate induces cell death selectively in leukemia cells without affecting the proliferation of normal lymphocytes. Incubation of human leukemia cells with ayanin diacetate induced G{sub 2}-M phase cell cycle arrest and apoptosis which was prevented by the non-specific caspase inhibitor z-VAD-fmk and reduced by the overexpression of Bcl-x{sub L}. Ayanin diacetate-induced cell death was found to be associated with: (i) loss of inner mitochondrial membrane potential, (ii) the release of cytochrome c, (iii) the activation of multiple caspases, (iv) cleavage of poly(ADP-ribose) polymerase and (v) the up-regulation of death receptors for TRAIL, DR4 and DR5. Moreover, the combined treatment with ayanin diacetate and TRAIL amplified cell death, compared to single treatments. These results provide a basis for further exploring the potential applications of this combination for the treatment of cancer.

  3. 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

  4. ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias.

    Science.gov (United States)

    Ishibashi, Tomohiko; Yokota, Takafumi; Tanaka, Hirokazu; Ichii, Michiko; Sudo, Takao; Satoh, Yusuke; Doi, Yukiko; Ueda, Tomoaki; Tanimura, Akira; Hamanaka, Yuri; Ezoe, Sachiko; Shibayama, Hirohiko; Oritani, Kenji; Kanakura, Yuzuru

    2016-04-01

    Reliable markers are essential to increase our understanding of the biological features of human hematopoietic stem cells and to facilitate the application of hematopoietic stem cells in the field of transplantation and regenerative medicine. We previously identified endothelial cell-selective adhesion molecule (ESAM) as a novel functional marker of hematopoietic stem cells in mice. Here, we found that ESAM can also be used to purify human hematopoietic stem cells from all the currently available sources (adult bone marrow, mobilized peripheral blood, and cord blood). Multipotent colony-forming units and long-term hematopoietic-reconstituting cells in immunodeficient mice were found exclusively in the ESAM(High) fraction of CD34(+)CD38(-) cells. The CD34(+)CD38(-) fraction of cord blood and collagenase-treated bone marrow contained cells exhibiting extremely high expression of ESAM; these cells are likely to be related to the endothelial lineage. Leukemia cell lines of erythroid and megakaryocyte origin, but not those of myeloid or lymphoid descent, were ESAM positive. However, high ESAM expression was observed in some primary acute myeloid leukemia cells. Furthermore, KG-1a myeloid leukemia cells switched from ESAM negative to ESAM positive with repeated leukemia reconstitution in vivo. Thus, ESAM is a useful marker for studying both human hematopoietic stem cells and leukemia cells. PMID:26774386

  5. Seroprevalence of feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) in shelter cats on the island of Newfoundland, Canada.

    Science.gov (United States)

    Munro, Hannah J; Berghuis, Lesley; Lang, Andrew S; Rogers, Laura; Whitney, Hugh

    2014-04-01

    Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are retroviruses found within domestic and wild cat populations. These viruses cause severe illnesses that eventually lead to death. Housing cats communally for long periods of time makes shelters at high risk for virus transmission among cats. We tested 548 cats from 5 different sites across the island of Newfoundland for FIV and FeLV. The overall seroprevalence was 2.2% and 6.2% for FIV and FeLV, respectively. Two sites had significantly higher seroprevalence of FeLV infection than the other 3 sites. Analysis of sequences from the FeLV env gene (envelope gene) from 6 positive cats showed that 4 fell within the FeLV subtype-A, while 2 sequences were most closely related to FeLV subtype-B and endogenous feline leukemia virus (en FeLV). Varying seroprevalence and the variation in sequences at different sites demonstrate that some shelters are at greater risk of FeLV infections and recombination can occur at sites of high seroprevalence. PMID:24688176

  6. Human Lyb-2 homolog CD72 is a marker for progenitor B-cell leukemias.

    Science.gov (United States)

    Schwarting, R; Castello, R; Moldenhauer, G; Pezzutto, A; von Hoegen, I; Ludwig, W D; Parnes, J R; Dörken, B

    1992-11-01

    S-HCL 2 is the prototype antibody of the recently defined CD72 cluster (human Lyb-2). Under nonreducing conditions, S-HCL 2 monoclonal antibody (mAb) precipitates a glycoprotein of 80-86 kDa. Under reducing conditions, a dimer of 43 and 39 kDa, with core proteins of 40 and 36 kDa, is precipitated. CD72 expression in normal and malignant tissues is different from expression of all other previously described human B-cell antigens. In peripheral blood and bone marrow, the antigen appears to be present on all B lymphocytes, with the exception of plasma cells. In tissue, immunohistochemical staining revealed positivity for all known B-cell compartments; however, pulpa macrophages of the spleen and von Kupffer cells exhibited distinct positivity for CD72 also. Among 83 malignant non-Hodgkin's lymphomas examined by immunohistochemistry (alkaline phosphatase anti-alkaline phosphatase technique), all 54 B-cell lymphomas, including precursor B-cell lymphomas, Burkitt's lymphomas, germinal center lymphomas, chronic lymphocytic leukemias, and hairy cell leukemias, were CD72 positive, but no T-cell lymphomas were. Flow cytometry study of more than 80 mainly acute leukemias (52 B-cell leukemias) showed reactivity with S-HCL 2 mAb over the full range of B-cell differentiation. In particular, very early B cells in cytoplasmic Ig (cIg)-negative, CD19-positive pre-pre-B-cell leukemias and hybrid leukemias (mixed myeloid and B-cell type) were consistently positive for CD72 on the cell surface. Therefore, CD72 may become an important marker for progenitor B-cell leukemias. PMID:1384316

  7. Cell killing by avian leukosis viruses.

    OpenAIRE

    Weller, S K; Temin, H M

    1981-01-01

    Infection of chicken cells with a cytopathic avian leukosis virus resulted in the detachment of killed cells from the culture dish. The detached, dead cells contained more unintegrated viral DNA than the attached cells. These results confirm the hypothesis that cell killing after infection with a cytopathic avian leukosis virus is associated with accumulation of large amounts of unintegrated viral DNA. No accumulation of large amounts of integrated viral DNA was found in cells infected with c...

  8. Use of different but overlapping determinants in a retrovirus receptor accounts for non-reciprocal interference between xenotropic and polytropic murine leukemia viruses

    Directory of Open Access Journals (Sweden)

    Van Hoeven Neal S

    2005-12-01

    Full Text Available Abstract Background Retrovirus infection depends on binding of the retroviral envelope (Env protein to specific cell-surface protein receptors. Interference, or superinfection resistance, is a frequent consequence of retroviral infection, and occurs when newly-synthesized Env binds to receptor proteins resulting in a block to entry by retroviruses that use the same receptors. Three groups of viruses demonstrate a non-reciprocal pattern of interference (NRI, which requires the existence of both a common receptor utilized by all viruses within the group, and a specific receptor that is used by a subset of viruses. In the case of amphotropic and 10A1 murine leukemia viruses (MLV, the common and specific receptors are the products of two related genes. In the case of avian sarcoma and leukosis virus types B, D, and E, the two receptors are distinct protein products of a single gene. NRI also occurs between xenotropic and polytropic MLV. The common receptor, Xpr1, has been identified, but a specific receptor has yet to be described. Results Using chimeric receptor proteins and interference studies, we have identified a region of Xpr1 that is uniquely utilized by xenotropic MLV and show that this receptor domain is required for non-reciprocal interference. Conclusion We propose a novel pattern of receptor usage by xenotropic and polytropic MLV to explain the NRI observed between these viruses. We propose that the specific and common receptor determinants for xenotropic and polytropic viruses are simultaneously present in discreet domains of a single Xpr1 protein.

  9. Synergistic interactions between HDAC and sirtuin inhibitors in human leukemia cells.

    Directory of Open Access Journals (Sweden)

    Michele Cea

    Full Text Available Aberrant histone deacetylase (HDAC activity is frequent in human leukemias. However, while classical, NAD(+-independent HDACs are an established therapeutic target, the relevance of NAD(+-dependent HDACs (sirtuins in leukemia treatment remains unclear. Here, we assessed the antileukemic activity of sirtuin inhibitors and of the NAD(+-lowering drug FK866, alone and in combination with traditional HDAC inhibitors. Primary leukemia cells, leukemia cell lines, healthy leukocytes and hematopoietic progenitors were treated with sirtuin inhibitors (sirtinol, cambinol, EX527 and with FK866, with or without addition of the HDAC inhibitors valproic acid, sodium butyrate, and vorinostat. Cell death was quantified by propidium iodide cell staining and subsequent flow-cytometry. Apoptosis induction was monitored by cell staining with FITC-Annexin-V/propidium iodide or with TMRE followed by flow-cytometric analysis, and by measuring caspase3/7 activity. Intracellular Bax was detected by flow-cytometry and western blotting. Cellular NAD(+ levels were measured by enzymatic cycling assays. Bax was overexpressed by retroviral transduction. Bax and SIRT1 were silenced by RNA-interference. Sirtuin inhibitors and FK866 synergistically enhanced HDAC inhibitor activity in leukemia cells, but not in healthy leukocytes and hematopoietic progenitors. In leukemia cells, HDAC inhibitors were found to induce upregulation of Bax, a pro-apoptotic Bcl2 family-member whose translocation to mitochondria is normally prevented by SIRT1. As a result, leukemia cells become sensitized to sirtuin inhibitor-induced apoptosis. In conclusion, NAD(+-independent HDACs and sirtuins cooperate in leukemia cells to avoid apoptosis. Combining sirtuin with HDAC inhibitors results in synergistic antileukemic activity that could be therapeutically exploited.

  10. A novel cell growth-promoting factor identified in a B cell leukemia cell line, BALL-1

    International Nuclear Information System (INIS)

    A novel leukemia cell growth-promoting activity has been identified in the culture supernatant from a human B cell leukemia cell line, BALL-1. The supernatant from unstimulated cultures of the BALL-1 cells significantly promoted the growth of 16 out of 24 leukemia/lymphoma cell lines of different lineages (T, B and non-lymphoid) in a minimal concentration of fetal bovine serum (FBS), and 5 out of 12 cases of fresh leukemia cells in FBS-free medium. The growth-promoting sieve filtration and dialysis. The MW of the factor was less than 10 kDa. The growth-promoting activity was heat and acid stable and resistant to trypsin treatment. The factor isolated from the BALL-1 supernatant was distinct from known polypeptide growth factors with MW below 10 kDa, such as epidermal growth factor, transforming growth factor α, insulin-like growth factor I (IGF-I), IGF-II and insulin, as determine by specific antibodies and by cell-growth-promoting tests. The factor is the BALL-1 supernatant did not promote the proliferation of normal human fresh peripheral blood lymphocytes or mouse fibroblast cell line, BALB/C 3T3. In addition to the BALL-1 supernatant, a similar growth-promoting activity was found in the culture supernatant from 13 of 17 leukemia/lymphoma cell lines tested. The activity in these culture supernatant promoted the growth of leukemia/lymphoma cell lines in autocrine and/or paracrine fashions. These observations suggest that the low MW cell growth-promoting activity found in the BALL-1 culture supernatant is mediated by a novel factor which may be responsible for the clonal expansion of particular leukemic clones. (author)

  11. Leukemia Inhibitory Factor Decreases the Arylamine N-Acetyltransferase Activity in Human Cumulus Granulosa Cells

    OpenAIRE

    Chang, Chi-Chen; Hsieh, Yao-Yuan; CHUNG, JING-GUNG; Tsai, Horng-Der; Tsai, Chang-Hai

    2001-01-01

    Purpose: To evaluate the activities of acetyl coenzyme A (AcCoA): arylamine N-acetyltransferase (NAT) of intact cumulus granulosa cells and the role of leukemia inhibitory factor (LIF) upon their NAT activities.

  12. Simple solid-phase radioimmunoassay for human leukemia-associated cell membrane antigens

    International Nuclear Information System (INIS)

    In the present study, a simple solid-phase radioimmunoassay was developed to determine detergent-extracted human leukemia-associated cell membrane antigens. In the assay, 96-well microtiter plates are coated with human leukemia cell membrane antigens containing a T cell leukemia or a non-T cell leukemia antigen in the presence of a detergent, and treated with 1.6% bovine serum albumin solution. The coated antigens were reacted with an appropriate murine monoclonal antibody (mAb). The bound mAb is determined by a second reaction with 125I-labeled F(ab')2 of goat anti-mouse Ig. The best antigen dose-dependent antibody binding results were obtained using the plates coated with antigens in the presence of taurocholate. In addition, the usefulness of the present assay with taurocholate during the purification of the antigens was demonstrated. (Auth.)

  13. Ginseng Extract Enhances Anti-cancer Effect of Cytarabine on Human Acute Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Yiju Hou

    2015-02-01

    Full Text Available Ginseng as a traditional medicine is well known to exhibit various pharmacological effects. Ginsenoside Rg3 is the active ingredient extracted from ginseng. The pharmacological modulatory effects of Rg3 on multidrug resistant cancer cells are reported in the present study. Cytarabine is a chemotherapeutic agent for the treatment of acute leukemia. However, this compound has serious side effects at high doses, for example hematopoiesis depression. In this study, using hl60 human leukemia cells, we investigated the possible synergistic anti-cancer effects between ginseng extract Rg3 and cytarabine on acute myeloid leukemia cells. Results of this study demonstrate that Rg3 can enhance the anti-proliferation effect of cytarabine on hl60 cells and may decrease the dosage of cytarabine needed for acute myeloid leukemia treatment.

  14. Characterisation of the Leukemic Stem Cell in a Murine Model of CALM/AF10 Positive Myeloid Leukemia

    OpenAIRE

    Deshpande, Aniruddha

    2006-01-01

    We have demonstrated, that an acute leukemia with a predominantly myeloid phenotype can be propagated by a progenitor with lymphoid characteristics in a mouse model of the t(10;11) (p13;q14) translocation. Mice transplanted with bone marrow retrovirally engineered to express the leukemia specific CALM/AF10 fusion gene consistently developed an acute leukemia with a short latency. The leukemia showed characteristic myeloid features such as the presence of myeloid marker positive cells infilt...

  15. Mogamulizumab for the treatment of adult T-cell leukemia/lymphoma

    Directory of Open Access Journals (Sweden)

    Yoshimitsu M

    2014-12-01

    Full Text Available Makoto Yoshimitsu, Naomichi Arima Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan Abstract: Adult T-cell leukemia/lymphoma (ATLL is a peripheral T-cell lymphoma caused by latent infection of human T-cell lymphotropic virus type 1. The outcome for ATLL is very poor, with a 3-year overall survival of approximately 24% with conventional chemotherapy; thus, there is an unmet need for developing new treatment options. Defucosylated humanized anti-CC chemokine receptor 4 (CCR4 antibody (KW-0761, mogamulizumab has been clinically available for the treatment of relapsed or refractory ATLL in Japan since 2012, and a Phase II study of mogamulizumab for patients with relapsed CCR4+ ATLL demonstrated a 50% objective response, a 30.8% complete response, and an acceptable safety profile. Allogeneic hematopoietic stem cell transplantation has been used to treat patients with ATLL, and mogamulizumab in combination with allogeneic hematopoietic stem cell transplantation has been used successfully in a limited number of patients to treat refractory or relapsed ATLL. The efficacy of combining mogamulizumab with standard chemotherapy (mLSG15 for patients with ATLL has also been examined, and the results have shown higher rates of complete response with the combined therapy (52% compared with for chemotherapy alone (33%. Mogamulizumab also has potential application in the treatment of human T-cell lymphotropic virus type 1-associated myelopathy/tropical paraparesis, Epstein–Barr virus-associated T-cell and natural killer-cell lymphoproliferative diseases, and peripheral and cutaneous T-cell lymphomas. Possible adverse events of mogamulizumab have been reported, such as cutaneous adverse reactions (including Stevens–Johnson syndrome, diffuse panbronchiolitis, reactivation of hepatitis B, and opportunistic infections. The treatment outcome of patients

  16. Natural resistance in mice against Friend leukemia cells. II. Studies with in vivo passaged interferon-sensitive and interferon-resistant cell clones

    International Nuclear Information System (INIS)

    Experiments were designed to test the presence of antitumor natural resistance (NR) in DBA/2 mice against highly oncogenic in vivo passaged histocompatible Friend leukemia cells (FLC-V). NR was measured in vivo as rapid clearance of radiolabeled cells from different organs or as growth inhibition in lethally irradiated mice. Interferon-sensitive (745) or interferon-resistant (3C18) lines were used. Organ clearance studies showed that young recipients eliminate cells more rapidly than old mice. Moreover, depressive (e.g., cyclophosphamide or carrageenen) or enhancing (e.g., poly (I:C) or Friend leukemia virus infection) agents of NR function modulate accordingly leukemia cell clearance. Similar results were obtained testing tumor growth in lethally irradiated hosts, although modulating agents were substantially less effective in this system. Both FLC-745-V and FLC-3C18-V lines were equally susceptible to NR. Therefore, these data provide further support to the hypothesis that exogenous IFN capable of suppressing the growth of both lines could act via enhancement of the NR function

  17. 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)

  18. Acute lymphoblastic leukemia cells that survive combination chemotherapy in vivo remain sensitive to allogeneic immune effects

    OpenAIRE

    Jansson, Johan; Hsu, Yu-Chiao; Kuzin, Igor I.; Campbell, Andrew; Mullen, Craig A.

    2010-01-01

    Allogeneic hematopoietic stem cell transplantation is often performed for patients with acute lymphoblastic leukemia (ALL) whose disease has relapsed after chemotherapy treatment. However, graft versus leukemia (GVL) effects in ALL are generally weak and the mechanisms of this weakness are unknown. These studies tested the hypothesis that ALL cells that have survived conventional chemotherapy in vivo acquire relative resistance to the allogeneic GVL effect. C57BL/6 mice were injected with mur...

  19. Ginseng Extract Enhances Anti-cancer Effect of Cytarabine on Human Acute Leukemia Cells

    OpenAIRE

    Yiju Hou; Xiaodong Liu; Zhonghai Yuan; Yan Li

    2015-01-01

    Ginseng as a traditional medicine is well known to exhibit various pharmacological effects. Ginsenoside Rg3 is the active ingredient extracted from ginseng. The pharmacological modulatory effects of Rg3 on multidrug resistant cancer cells are reported in the present study. Cytarabine is a chemotherapeutic agent for the treatment of acute leukemia. However, this compound has serious side effects at high doses, for example hematopoiesis depression. In this study, using hl60 human leukemia cells...

  20. Induced transdifferentiation of human B-leukemia/lymphoma cell lines and inhibition of leukemogenicity

    OpenAIRE

    Rapino, Francesca

    2013-01-01

    B-cell malignancies encompass a wide variety of distinct diseases including Non Hodgkin lymphoma (NHL) and leukemia. Currently, chemotherapy, radiation and anti-CD20 antibody treatment are the mainstays of B-cell lymphoma and leukemia therapy. However, the fact that a large number of patients are eventually not cured justifies the search for novel and more effective therapeutic approaches. Although induction of differentiation has been shown to be effective in several tum...

  1. Flow cytometric immunophenotypic characteristics of plasma cell leukemia

    Directory of Open Access Journals (Sweden)

    Barbara Kruk

    2011-04-01

    Full Text Available The aim of this prospective study was to define the flow cytometric characteristics of simultaneously investigated bone marrow and peripheral blood plasma cells antigens expression in 36 plasma cell leukemia (PCL patients. The immunophenotypic profile of plasma cells was determined with a panel of monoclonal antibodies. The antigen expression intensity was calculated as relative fluorescence intensity (RFI. Bone marrow plasma cells showed expression of particular antigens in the following proportion of cases: CD49d 100%, CD29 94%, CD54 93%, CD44 83%, CD56 60%, CD18 26%, CD11b 29%, CD11a 19%, CD117 27%, CD71 30%, CD126 100% and CD19 0%, while the expression of those antigens on peripheral blood plasma cells was present in the following percentage of patients: CD49d 100%, CD29 96%, CD54 93%, CD44 95%, CD56 56%, CD18 50%, CD11b 53%, CD11a 29%, CD117 26%, CD71 28%, CD126 100% and CD19 0%. The expression of CD54 was significantly higher than that of adhesion molecules belonging to the integrin b2 family: CD11a, CD18 and CD11b, on both bone marrow and peripheral blood cells (p < 0.01. Expression of CD18, CD11a and CD11b was differential between two cell compartments: lower on bone marrow and higher on peripheral blood cells. We found that plasma cells in the bone marrow of patients with plasma cell leukaemia showed significantly greater granularity and size than those in the peripheral blood (p = 0.0001 and p = 0.04, respectively. However, no differences in cell size or granularity were revealed between bone marrow plasma cells from patients with PCL and multiple myeloma. In conclusion, impaired expression of adhesion molecules such as CD11a/CD18 (LFA-1 or CD56 may explain hematogenic dissemination characterizing PCL. The following pattern of adhesion molecule expression according to the proportion of plasma cells expressing a given antigen in peripheral blood and bone marrow and arranged in diminishing order may be established: CD49d > CD44 > CD54

  2. 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. ...

  3. 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. ...

  4. Susceptibility of cell lines to avian viruses

    Directory of Open Access Journals (Sweden)

    Simoni Isabela Cristina

    1999-01-01

    Full Text Available The susceptibility of the five cell lines - IB-RS-2, RK-13, Vero, BHK-21, CER - to reovirus S1133 and infectious bursal disease virus (IBDV vaccine GBV-8 strain was studied to better define satisfactory and sensitive cell culture systems. Cultures were compared for presence of CPE, virus titers and detection of viral RNA. CPE and viral RNA were detected in CER and BHK-21 cells after reovirus inoculation and in RK-13 cell line after IBDV inoculation and with high virus titers. Virus replication by production of low virus titers occurred in IB-RS-2 and Vero cells with reovirus and in BHK-21 cell line with IBDV.

  5. Oncogenes and RNA splicing of human tumor viruses

    OpenAIRE

    Ajiro, Masahiko; Zheng, Zhi-Ming

    2014-01-01

    Approximately 10.8% of human cancers are associated with infection by an oncogenic virus. These viruses include human papillomavirus (HPV), Epstein–Barr virus (EBV), Merkel cell polyomavirus (MCV), human T-cell leukemia virus 1 (HTLV-1), Kaposi's sarcoma-associated herpesvirus (KSHV), hepatitis C virus (HCV) and hepatitis B virus (HBV). These oncogenic viruses, with the exception of HCV, require the host RNA splicing machinery in order to exercise their oncogenic activities, a strategy that a...

  6. Resistance to cyclopentenylcytosine in murine leukemia L1210 cells.

    Science.gov (United States)

    Zhang, H; Cooney, D A; Zhang, M H; Ahluwalia, G; Ford, H; Johns, D G

    1993-12-01

    Cyclopentenyl cytosine (CPEC) exhibits oncological activity in murine and human tumor cells and has now entered Phase I clinical trials. Its mode of action as an antitumor agent appears to be inhibition by its triphosphate (CPEC-TP) of CTP synthase, the enzyme which converts UTP to CTP. In an attempt to elucidate the mechanism of resistance to CPEC, a murine leukemia cell line resistant to CPEC (L1210/CPEC) was developed by N-methyl-N-nitro-N-nitrosoguanidine-induced mutagenesis and subsequent selection by cultivation of the L1210 cells in the presence of 2 microM CPEC. Resistant clones were maintained in CPEC-free medium for 6 generations before biochemical studies were performed. The resistant clone selected for further studies was approximately 13,000-fold less sensitive to growth inhibition by CPEC than the parental cells, and the concentration of CPEC required to deplete CTP in the resistant cells was 50-fold higher than in the sensitive cells. A comparison of the kinetic properties of CTP synthase from sensitive and resistant cells indicated alteration in the properties of the enzyme from the latter; the median inhibitory concentration for CPEC-TP increased from 2 to 14 microM, Km for UTP decreased from 126 to 50 microM, and Vmax increased 12-fold from 0.2 to 2.3 nmol/mg/min. Northern blot analyses of polyadenylated RNA from the resistant and sensitive cells indicated a 3-fold increase in transcripts of the CTP synthase gene in the resistant line. Consistent with these alterations in the properties of the enzyme, the resistant cells exhibited significantly expanded CTP and dCTP pools (4- 5-fold) when compared with the sensitive cells. No change was observed, however, in the properties of uridine-cytidine kinase, the enzyme responsible for the initial phosphorylation of CPEC; despite this, however, cellular uptake of CPEC was greatly decreased, and phosphorylation of CPEC and its incorporation into RNA were 10-fold less than in the parental cells. These latter

  7. Evolutionary dynamics of endogenous feline leukemia virus proliferation among species of the domestic cat lineage

    International Nuclear Information System (INIS)

    Endogenous feline leukemia viruses (enFeLVs) occur in the germ lines of the domestic cat and related wild species (genus Felis). We sequenced the long terminal repeats and part of the env region of enFeLVs in domestic cats and five wild species. A total of 305 enFeLV sequences were generated across 17 individuals, demonstrating considerable diversity within two major clades. Distinct proliferations of enFeLVs occurred before and after the black-footed cat diverged from the other species. Diversity of enFeLVs was limited for the sand cat and jungle cat suggesting that proliferation of enFeLVs occurred within these species after they diverged. Relationships among enFeLVs were congruent with host species relationships except for the jungle cat, which carried only enFeLVs from a lineage that recently invaded the germline (enFeLV-AGTT). Comparison of wildcat and domestic cat enFeLVs indicated that a distinctive germ line invasion of enFeLVs has not occurred since the cat was domesticated.

  8. Seroprevalence of bovine leukemia virus (BLV) infection in dairy cattle in Isfahan Province, Iran.

    Science.gov (United States)

    Morovati, Hassan; Shirvani, Edris; Noaman, Vahid; Lotfi, Mohsen; Kamalzadeh, Morteza; Hatami, Alireza; Bahreyari, Masoume; Shahramyar, Zahra; Morovati, Mohammad H; Azimi, Mahmoud; Sakhaei, Davoud

    2012-08-01

    Bovine leukemia virus (BLV), the causative agent of enzootic bovine leukosis (EBL) is an exogenous C-type oncovirus in the Retroviridae family. It causes significant economic losses associated with the costs of control and eradication programs due to carcass condemnation at slaughter and restrictions of export of cattle and semen to importing countries. The main objective of this research was to determine the seroprevalence of BLV infection in cattle herds in central region of Iran (Isfahan province) using a commercial enzyme-linked immunosorbent assay (ELISA) to detect serum antibodies against BLV. Samples of blood serum were collected from 403 female dairy cattle (Holstein-Friesian) from 21 livestock farms and 303 animals (81.9%) were BLV seropositive. A significant association was found between age as a potential risk factor and BVL seroprevalence with animals ≥ 4 years (86.6%) having a significantly (χ(2) = 35.6, p 0.1). It is concluded that BLV infection is a very common problem in the study area. Hence, control measures should be instituted to combat the disease and further studies are required to investigate the impact of this disease on dairy production in the country. PMID:22210288

  9. Solution Properties of Murine Leukemia Virus Gag Protein: Differences from HIV-1 Gag

    Energy Technology Data Exchange (ETDEWEB)

    Datta, Siddhartha A.K.; Zuo, Xiaobing; Clark, Patrick K.; Campbell, Stephen J.; Wang, Yun-Xing; Rein, Alan (SAIC); (NCI)

    2012-05-09

    Immature retrovirus particles are assembled from the multidomain Gag protein. In these particles, the Gag proteins are arranged radially as elongated rods. We have previously characterized the properties of HIV-1 Gag in solution. In the absence of nucleic acid, HIV-1 Gag displays moderately weak interprotein interactions, existing in monomer-dimer equilibrium. Neutron scattering and hydrodynamic studies suggest that the protein is compact, and biochemical studies indicate that the two ends can approach close in three-dimensional space, implying the need for a significant conformational change during assembly. We now describe the properties of the Gag protein of Moloney murine leukemia virus (MLV), a gammaretrovirus. We found that this protein is very different from HIV-1 Gag: it has much weaker protein-protein interaction and is predominantly monomeric in solution. This has allowed us to study the protein by small-angle X-ray scattering and to build a low-resolution molecular envelope for the protein. We found that MLV Gag is extended in solution, with an axial ratio of {approx}7, comparable to its dimensions in immature particles. Mutational analysis suggests that runs of prolines in its matrix and p12 domains and the highly charged stretch at the C terminus of its capsid domain all contribute to this extended conformation. These differences between MLV Gag and HIV-1 Gag and their implications for retroviral assembly are discussed.

  10. Survey of feline leukemia virus and feline coronaviruses in captive neotropical wild felids from Southern Brazil.

    Science.gov (United States)

    Guimaraes, Ana M S; Brandão, Paulo E; de Moraes, Wanderlei; Cubas, Zalmir S; Santos, Leonilda C; Villarreal, Laura Y B; Robes, Rogério R; Coelho, Fabiana M; Resende, Mauricio; Santos, Renata C F; Oliveira, Rosangela C; Yamaguti, Mauricio; Marques, Lucas M; Neto, Renata L; Buzinhani, Melissa; Marques, Regina; Messick, Joanne B; Biondo, Alexander W; Timenetsky, Jorge

    2009-06-01

    A total of 57 captive neotropical felids (one Leopardus geoffroyi, 14 Leopardus pardalis, 17 Leopardus wiedii, 22 Leopardus tigrinus, and three Puma yagouaroundi) from the Itaipu Binacional Wildlife Research Center (Refúgio Bela Vista, Southern Brazil) were anesthetized for blood collection. Feces samples were available for 44 animals, including one L. geoffroyi, eight L. pardalis, 14 L. wiedii, 20 L. tigrinus, and one P. yagouaroundi. Total DNA and RNA were extracted from blood and feces, respectively, using commercial kits. Blood DNA samples were evaluated by polymerase chain reaction (PCR) for feline leukemia virus (FeLV) proviral DNA, whereas reverse transcriptase-PCR was run on fecal samples for detection of coronavirus RNA. None of the samples were positive for coronaviruses. A male L. pardalis and a female L. tigrinus were positive for FeLV proviral DNA, and identities of PCR products were confirmed by sequencing. This is the first evidence of FeLV proviral DNA in these species in Southern Brazil. PMID:19569487

  11. Murine Leukemia Virus Uses TREX Components for Efficient Nuclear Export of Unspliced Viral Transcripts

    Directory of Open Access Journals (Sweden)

    Toshie Sakuma

    2014-03-01

    Full Text Available Previously we reported that nuclear export of both unspliced and spliced murine leukemia virus (MLV transcripts depends on the nuclear export factor (NXF1 pathway. Although the mRNA export complex TREX, which contains Aly/REF, UAP56, and the THO complex, is involved in the NXF1-mediated nuclear export of cellular mRNAs, its contribution to the export of MLV mRNA transcripts remains poorly understood. Here, we studied the involvement of TREX components in the export of MLV transcripts. Depletion of UAP56, but not Aly/REF, reduced the level of both unspliced and spliced viral transcripts in the cytoplasm. Interestingly, depletion of THO components, including THOC5 and THOC7, affected only unspliced viral transcripts in the cytoplasm. Moreover, the RNA immunoprecipitation assay showed that only the unspliced viral transcript interacted with THOC5. These results imply that MLV requires UAP56, THOC5 and THOC7, in addition to NXF1, for nuclear export of viral transcripts. Given that naturally intronless mRNAs, but not bulk mRNAs, require THOC5 for nuclear export, it is plausible that THOC5 plays a key role in the export of unspliced MLV transcripts.

  12. Fraction of bovine leukemia virus-infected dairy cattle developing enzootic bovine leukosis.

    Science.gov (United States)

    Tsutsui, Toshiyuki; Kobayashi, Sota; Hayama, Yoko; Yamamoto, Takehisa

    2016-02-01

    Enzootic bovine leucosis (EBL) is a transmissible disease caused by the bovine leukemia virus that is prevalent in cattle herds in many countries. Only a small fraction of infected animals develops clinical symptoms, such as malignant lymphosarcoma, after a long incubation period. In the present study, we aimed to determine the fraction of EBL-infected dairy cattle that develop lymphosarcoma and the length of the incubation period before clinical symptoms emerge. These parameters were determined by a mathematical modeling approach based on the maximum-likelihood estimation method, using the results of a nationwide serological survey of prevalence in cattle and passive surveillance records. The best-fit distribution to estimate the disease incubation period was determined to be the Weibull distribution, with a median and average incubation period of 7.0 years. The fraction of infected animals developing clinical disease was estimated to be 1.4% with a 95% confidence interval of 1.2-1.6%. The parameters estimated here contribute to an examination of efficient control strategies making quantitative evaluation available. PMID:26754928

  13. Structural basis of suppression of host translation termination by Moloney Murine Leukemia Virus

    Science.gov (United States)

    Tang, Xuhua; Zhu, Yiping; Baker, Stacey L.; Bowler, Matthew W.; Chen, Benjamin Jieming; Chen, Chen; Hogg, J. Robert; Goff, Stephen P.; Song, Haiwei

    2016-06-01

    Retroviral reverse transcriptase (RT) of Moloney murine leukemia virus (MoMLV) is expressed in the form of a large Gag-Pol precursor protein by suppression of translational termination in which the maximal efficiency of stop codon read-through depends on the interaction between MoMLV RT and peptidyl release factor 1 (eRF1). Here, we report the crystal structure of MoMLV RT in complex with eRF1. The MoMLV RT interacts with the C-terminal domain of eRF1 via its RNase H domain to sterically occlude the binding of peptidyl release factor 3 (eRF3) to eRF1. Promotion of read-through by MoMLV RNase H prevents nonsense-mediated mRNA decay (NMD) of mRNAs. Comparison of our structure with that of HIV RT explains why HIV RT cannot interact with eRF1. Our results provide a mechanistic view of how MoMLV manipulates the host translation termination machinery for the synthesis of its own proteins.

  14. EFFECTS OF CURCUMIN ON PROLIFERATION AND APOPTOSIS IN ACUTE MYELOID LEUKEMIA CELLS HL-60

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To investigate the curcumin killing leukemia cells in vitro,. Methods: The myeloid leukemic cell line HL-60 was studied by using cell culture, flow cytometrydetermining DNA content and TUNEL method measuring apoptotic cell percentage. Results: The data showed that curcumin selectively inhibited proliferation of acute myeloid leukemia (AML) HL-60 cell lines in a dose- and time-dependent manner. The growth inhibition rate was gradually increased and reached the peak at concentration of 25 m mol/L curcumin at 24h. The sub-G1 peak appeared after 12h treatment and was increased to 34.4% at 24h. The TUNEL method further certified that apoptotic cells reached 41% at the same phase. Conclusion: curcumin possesses obvious potent of anti-leukemia cell proliferation, which is contributed to the induction of HL-60 cells apoptosis. The concentration and action time of curcumin in vitro provide some reference for clinical use.

  15. Immunological reactivity of leukemia afflicted animals under the effect of gamma-ray sterilized malignant cells

    International Nuclear Information System (INIS)

    The employment of ionizing radiation or cytostatics for the treatment of malignant neoplasms leads to the cessation of the processes of division in part of the malignant cells. Cells sterilized in this manner interact with the malignant cells that have remained alive. To elucidate some mechanisms of this interrelationships studies were undertaken on mice with transplantational leukemia L 1210. Since the intraperitoneal administration of 107 sterile leukemia cells mixed with 104 live cells results in prolongation of survival of the mice in this group as compared with mice injected with live cells only. The question arises whether immune mechanisms are involved in these phenomena. Studies on the specific immunological activity indicate that in the group treated with a mixture of sterilized and live cells the number of positive cytotoxic reactions increases as regards leukemia cells; the nonspecific immune reactivity remains unaffected. (author)

  16. Emodin Induces Apoptotic Death in Murine Myelomonocytic Leukemia WEHI-3 Cells In Vitro and Enhances Phagocytosis in Leukemia Mice In Vivo

    Directory of Open Access Journals (Sweden)

    Yuan-Chang Chang

    2011-01-01

    Full Text Available Emodin is one of major compounds in rhubarb (Rheum palmatum L., a plant used as herbal medicine in Chinese population. Although many reports have shown that emodin exhibits anticancer activity in many tumor cell types, there is no available information addressing emodin-affected apoptotic responses in the murine leukemia cell line (WEHI-3 and modulation of the immune response in leukemia mice. We investigated that emodin induced cytotoxic effects in vitro and affected WEHI-3 cells in vivo. This study showed that emodin decreased viability and induced DNA fragmentation in WEHI-3 cells. Cells after exposure to emodin for 24 h have shown chromatin condensation and DNA damage. Emodin stimulated the productions of ROS and Ca2+ and reduced the level of ΔΨm by flow cytometry. Our results from Western blotting suggest that emodin triggered apoptosis of WEHI-3 cells through the endoplasmic reticulum (ER stress, caspase cascade-dependent and -independent mitochondrial pathways. In in vivo study, emodin enhanced the levels of B cells and monocytes, and it also reduced the weights of liver and spleen compared with leukemia mice. Emodin promoted phagocytic activity by monocytes and macrophages in comparison to the leukemia mice group. In conclusions, emodin induced apoptotic death in murine leukemia WEHI-3 cells and enhanced phagocytosis in the leukemia animal model.

  17. Mutagenesis analysis of the murine leukemia virus matrix protein: identification of regions important for membrane localization and intracellular transport.

    Science.gov (United States)

    Soneoka, Y; Kingsman, S M; Kingsman, A J

    1997-07-01

    We have created two sets of substitution mutations in the Moloney murine leukemia virus (Mo-MuLV) matrix protein in order to identify domains involved in association with the plasma membrane and in incorporation of the viral envelope glycoproteins into virus particles. The first set of mutations was targeted at putative membrane-associating regions similar to those of the human immunodeficiency virus type 1 matrix protein, which include a polybasic region at the N terminus of the Mo-MuLV matrix protein and two regions predicted to form beta strands. The second set of mutations was created within hydrophobic residues to test for the production of virus particles lacking envelope proteins, with the speculation of an involvement of the membrane-spanning region of the envelope protein in incorporation into virus particles. We have found that mutation of the N-terminal polybasic region redirected virus assembly to the cytoplasm, and we show that tryptophan residues may also play a significant role in the intracellular transport of the matrix protein. In total, 21 mutants of the Mo-MuLV matrix protein were produced, but we did not observe any mutant virus particles lacking the envelope glycoproteins, suggesting that a direct interaction between the Mo-MuLV matrix protein and envelope proteins either may not exist or may occur through multiple redundant interactions. PMID:9188629

  18. Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia

    International Nuclear Information System (INIS)

    To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC1280 library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 μM drug concentration. Only one of these compounds, quinacrine, showed low activity in normal PBMCs and was therefore selected for further preclinical evaluation. Mining the NCI-60 and the NextBio databases demonstrated leukemia sensitivity and the ability of quinacrine to reverse myeloid leukemia gene expression. Mechanistic exploration was performed using the NextBio bioinformatic software using gene expression analysis of drug exposed acute myeloid leukemia cultures (HL-60) in the database. Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation. The highest drug–drug correlation was to ellipticine, a known RNA polymerase I inhibitor. These results were validated by additional gene expression analysis performed in-house. Quinacrine induced early inhibition of protein synthesis supporting these predictions. The results suggest that quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis

  19. Graft-versus-leukemia effects associated with detectable Wilms tumor-1–specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia

    OpenAIRE

    Rezvani, Katayoun; Yong, Agnes S.M.; Savani, Bipin N.; Mielke, Stephan; Keyvanfar, Keyvan; Gostick, Emma; Price, David A; Douek, Daniel C.; Barrett, A. John

    2007-01-01

    To determine whether the leukemia-associated Wilms tumor antigen (WT1) contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8+ T-cell responses to WT1 in 10 human lymphocyte antigen (HLA)–A*0201–positive ALL patients during the early phase of immune recovery after SCT (days 30-120). Seven of 10 patients had detectable WT1 expression in their peripheral blood (PB) before SCT by quantitative rev...

  20. Viruses, dendritic cells and the lung

    Directory of Open Access Journals (Sweden)

    Graham Barney S

    2001-06-01

    Full Text Available Abstract The interaction between viruses and dendritic cells (DCs is varied and complex. DCs are key elements in the development of a host response to pathogens such as viruses, but viruses have developed survival tactics to either evade or diminish the immune system that functions to kill and eliminate these micro-organisms. In the present review we summarize current concepts regarding the function of DCs in the immune system, our understanding of how viruses alter DC function to attenuate both the virus-specific and global immune response, and how we may be able to exploit DC function to prevent or treat viral infections.

  1. Ezrin dephosphorylation/downregulation contributes to ursolic acid-mediated cell death in human leukemia cells

    International Nuclear Information System (INIS)

    Ezrin links the actin filaments with the cell membrane and has a functional role in the apoptotic process. It appears clear that ezrin is directly associated with Fas, leading to activation of caspase cascade and cell death. However, the exact role of ezrin in ursolic acid (UA)-induced apoptosis remains unclear. In this study, we show for the first time that UA induces apoptosis in both transformed and primary leukemia cells through dephosphorylation/downregulation of ezrin, association and polarized colocalization of Fas and ezrin, as well as formation of death-inducing signaling complex. These events are dependent on Rho-ROCK1 signaling pathway. Knockdown of ezrin enhanced cell death mediated by UA, whereas overexpression of ezrin attenuated UA-induced apoptosis. Our in vivo study also showed that UA-mediated inhibition of tumor growth of mouse leukemia xenograft model is in association with the dephosphorylation/downregulation of ezrin. Such findings suggest that the cytoskeletal protein ezrin may represent an attractive target for UA-mediated lethality in human leukemia cells

  2. 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

  3. Comparative examination of cats with feline leukemia virus-associated enteritis and other relevant forms of feline enteritis.

    Science.gov (United States)

    Kipar, A; Kremendahl, J; Jackson, M L; Reinacher, M

    2001-07-01

    Cats with feline leukemia virus (FeLV)-associated enteritis (FAE), enteritis of other known viral etiology (parvovirus [PV], enteric coronavirus [CoV]), and enteritis of unknown etiology with histologic features similar to those of FAE and PV enteritis (EUE) and FeLV-negative and FeLV-positive cats without enterocyte alterations were examined. Amount and types of infiltrating leukocytes in the jejunum and activity and cellular constituents of mesenteric lymph nodes, spleen, and bone marrow were determined. PV and CoV infections were confirmed by immunohistologic demonstration of PV and CoV antigen, ultrastructural demonstration of viral particles in the intestinal content, and in situ hybridization for PV genome. FeLV infection was detected by immunohistology for gp70, p27, and p15E. Latent FeLV infection was excluded by polymerase chain reaction methods for exogenous FeLV DNA. Enterocyte lesions involved the crypts in cats with PV enteritis, FAE, and EUE and the villous tips in cats with CoV enteritis. Inflammatory infiltration was generally dominated by mononuclear cells and was moderate in the unaltered intestine and in cats with PV enteritis and marked in cats with FAE, CoV enteritis, and EUE. In cats with EUE, myeloid/histiocyte antigen-positive macrophages were relatively numerous, suggesting recruitment of peripheral blood monocytes. Lymphoid tissues were depleted in cats with PV enteritis and with EUE but were normal or hyperplastic in cats with FAE. Bone marrow activity was decreased in cats with PV enteritis; in cats with FAE or EUE and in FeLV-positive cats without enterocyte alterations, activity was slightly increased. In cats with FAE and PV enteritis, a T-cell-dominated response prevailed. EUE showed some parallels to human inflammatory bowel disease, indicating a potential harmful effect of infiltrating macrophages on the intestinal epithelium. PMID:11467470

  4. Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias

    DEFF Research Database (Denmark)

    Nicolini, Franck Emmanuel; Basak, Grzegorz W; Soverini, Simona;

    2011-01-01

    , still alive]) for those with chronic myeloid leukemia in the blast phase and 7.4 months (range 1.4 months to not reached [ie, still alive]) for those with Philadelphia chromosome-positive acute lymphoblastic leukemia but has not yet been reached for those in the chronic and accelerated phases of chronic...... myeloid leukemia. The occurrence of chronic GVHD had a positive impact on overall survival (P = .047). Transplant-related mortality rates were low. Multivariate analysis identified only blast phase at transplantation (hazard ratio 3.68, P = .0011) and unrelated stem cell donor (hazard ratio 2.98, P = .011...

  5. Transforming human blood stem and progenitor cells: A new way forward in leukemia modeling

    OpenAIRE

    Mulloy, James C.; Wunderlich, Mark; Zheng, Yi; Wei, Junping

    2008-01-01

    MLL-AF9 (MA9) is a leukemia fusion gene formed upon translocation of the AF9 gene on chromosome 9 and the MLL gene on chromosome 11. MA9 is commonly found in acute myeloid leukemia (AML) and occasionally in acute lymphoid leukemia and is associated with intermediate to poor outcome. The specific signaling pathways downstream of MA9 are still poorly understood. We have recently described a model system whereby we expressed the MA9 fusion gene in human CD34+ Umbilical Cord Blood (UCB) cells and...

  6. Donor cell leukemia after allogeneic peripheral blood stem cell transplantation: a case report and literature review.

    Science.gov (United States)

    Murata, Makoto; Ishikawa, Yuichi; Ohashi, Haruhiko; Terakura, Seitaro; Ozeki, Kazutaka; Kiyoi, Hitoshi; Naoe, Tomoki

    2008-07-01

    A 49-year-old male developed recurrent acute myeloid leukemia 27 months after allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA-identical brother. The immunophenotype of the blastic cell population was incompatible with that of the pre-transplant blast cells; a mutation in C/EBPA gene was found in the pre-transplant blast cells that was not present in the post-transplant blast cells, and short tandem repeat analysis of marrow cells, which included 71% blasts, showed complete donor chimera. Thus, this recipient developed donor cell leukemia (DCL). The donor was healthy when DCL developed in the recipient as well as before donation of the peripheral blood stem cells. Only five cases of DCL after PBSCT have been reported in the literature. As a mechanism for the development of DCL, a vigorous proliferative demand on the donor cells, which often correlates with a higher likelihood of replication error or mutation, has been proposed. Peripheral blood stem cells might have an advantage in that they are associated with a low incidence of DCL development because PBSCT recipients receive a higher total cell dose than recipients of bone marrow or cord blood cells. PMID:18470599

  7. Anticancer activity of cryptotanshinone on acute lymphoblastic leukemia cells.

    Science.gov (United States)

    Wu, Ching-Fen; Klauck, Sabine M; Efferth, Thomas

    2016-09-01

    Cryptotanshinone, a well-known diterpene quinone from a widely used traditional Chinese herb named Salvia miltiorrhiza, has been reported for its therapeutical potentials on diverse activities. In this study, pharmacological effects of cryptotanshinone on acute lymphoblastic leukemia cells were investigated. IC50 values of 5.0 and 4.8 were obtained in CEM/ADR5000 and CCRF-CEM. Microarray-based mRNA expression revealed that cryptotanshinone regulated genes associated with cell cycle, DNA damage, reactive oxygen species (ROS), NFκB signaling and cellular movement. The involvement of these pathways in the mode of action of cryptotanshinone was subsequently validated by additional independent in vitro studies. Cryptotanshinone stimulated ROS generation and induced DNA damage. It arrested cells in G2/M phase of the cell cycle and induced apoptosis as measured by annexin V-FITC-conjugating fluorescence. The induction of the intrinsic apoptotic pathway by cryptotanshinone was proved by loss of mitochondrial membrane potential and increased cleavage of caspase 3/7, caspase 9 and poly ADP ribose polymerase (PARP). DNA-binding motif analysis of the microarray-retrieved deregulated genes in the promoter region revealed NFκB as potential transcription factor involved in cryptotanshinone's mode of action. Molecular docking and Western blotting provided supportive evidence, suggesting that cryptotanshinone binds to IKK-β and inhibits the translocation of p65 from the cytosol to the nucleus. In addition, cryptotanshinone inhibited cellular movement as shown by a fibronectin-based cellular adhesion assay, indicating that this compound exerts anti-invasive features. In conclusion, cryptotanshinone exerts profound cytotoxicity, which is caused by multispecific modes of actions, including G2/M arrest, apoptosis and inhibition of cellular movement. The inhibitory activities of this compound may be explained by inhibition of NFκB, which orchestrates all these mechanisms. PMID

  8. Knockdown of WAVE1 enhances apoptosis of leukemia cells by downregulating autophagy.

    Science.gov (United States)

    Zhang, Zhaoxia; Wu, Benqing; Chai, Wenwen; Cao, Lizhi; Wang, Yangping; Yu, Yan; Yang, Liangchun

    2016-06-01

    Chemoresistance of leukemia constitutes a great challenge for successful treatment of leukemia. Autophagy has recently attracted increasing attention for its role in conferring resistance to various conventional anti-neoplastic regiments. In the present study, the authors showed that WAVE1, a member of WASP family verprolin-homologous proteins, is a critical regulator of chemoresistance during autophagy. It is positively correlated with clinical status in pediatric acute myeloblastic leukemia (AML) and leukemia cell lines. The knockdown of WAVE1 expression decreased autophagy was accompanied by an upregulation of autophagic marker microtubule-associated protein light chain 3 (LC3)-Ⅱ, a degradation of SQSTM1/sequestosome 1 (p62) and the formation of autophagosomes. Moreover, a suppression of WAVE1 expression increased the sensitivity of leukemia cells to chemotherapy and apoptosis, and depletion of WAVE1 expression promoted the translocation of Bcl-2 from mitochondria into the cytoplasm. In addition, a knockdown of PI3K-Ⅲ expression significantly inhibited WAVE1-mediated autophagy. Furthermore, suppression of WAVE1 expression blocked the interactions between Beclin1 and PI3K-Ⅲ and the disassociation of Beclin1-Bcl-2 during enhanced autophagy. The above results suggested that WAVE1 is a critical pro-autophagic protein capable of enhancing cell survival and regulating chemoresistance in leukemia cells potentially through the Beclin1/Bcl-2 and Beclin1/PI3K-Ⅲ complex-dependent pathways. PMID:27035872

  9. RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Houcai; Yu, Jing; Zhang, Lixia; Xiong, Yuanyuan; Chen, Shuying; Xing, Haiyan; Tian, Zheng; Tang, Kejing; Wei, Hui; Rao, Qing; Wang, Min; Wang, Jianxiang, E-mail: wangjx@ihcams.ac.cn

    2014-04-18

    Highlights: • RPS27a expression was up-regulated in advanced-phase CML and AL patients. • RPS27a knockdown changed biological property of K562 and K562/G01 cells. • RPS27a knockdown affected Raf/MEK/ERK, P21 and BCL-2 signaling pathways. • RPS27a knockdown may be applicable for new combination therapy in CML patients. - Abstract: Ribosomal protein S27a (RPS27a) could perform extra-ribosomal functions besides imparting a role in ribosome biogenesis and post-translational modifications of proteins. The high expression level of RPS27a was reported in solid tumors, and we found that the expression level of RPS27a was up-regulated in advanced-phase chronic myeloid leukemia (CML) and acute leukemia (AL) patients. In this study, we explored the function of RPS27a in leukemia cells by using CML cell line K562 cells and its imatinib resistant cell line K562/G01 cells. It was observed that the expression level of RPS27a was high in K562 cells and even higher in K562/G01 cells. Further analysis revealed that RPS27a knockdown by shRNA in both K562 and K562G01 cells inhibited the cell viability, induced cell cycle arrest at S and G2/M phases and increased cell apoptosis induced by imatinib. Combination of shRNA with imatinib treatment could lead to more cleaved PARP and cleaved caspase-3 expression in RPS27a knockdown cells. Further, it was found that phospho-ERK(p-ERK) and BCL-2 were down-regulated and P21 up-regulated in RPS27a knockdown cells. In conclusion, RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells. It appears that drugs targeting RPS27a combining with tyrosine kinase inhibitor (TKI) might represent a novel therapy strategy in TKI resistant CML patients.

  10. Immunophenotyping of mature T/NK cell neoplasm presenting as leukemia

    Directory of Open Access Journals (Sweden)

    S Gujral

    2010-01-01

    Full Text Available Introduction : Mature T/NK cell lymphomas (MTNKL presenting as leukemia are rare and show considerable overlapping of clinical, morphological and immunophenotypic features. AIM: Critical analysis of the morphology and immunophenotypic profile of MTNKL. Materials and Methods : We reviewed 380 consecutive cases of mature lymphoid neoplasm that presented as leukemia and were diagnosed on morphology and immunophenotyping of bone marrow and/or peripheral blood samples. Results : Peripheral blood and bone marrow involvement was seen in all cases. MTNKL constituted 4% (nine cases of all mature lymphoid neoplasms presenting as leukemia. It included four cases of T-large granular leukemia (T-LGL, two of T-cell prolymphocytic leukemia small cell variant (T-PLL, two of adult T-cell leukemia/lymphoma (ATLL and one of primary cutaneous gamma delta T-cell lymphoma (PCGDTCL. T-LGL revealed CD4-/CD8+ phenotype in three, and CD4+/CD8+ phenotype in one case. CD56 was absent in all the cases of T-LGL. One case of T- PLL small cell variant showed CD4+/CD8- phenotype, while the other revealed CD4-/CD8+ phenotype. Both cases of ATLL showed CD4+/CD8+/CD25+ phenotype. The single case of PCGDTCL showed CD4-/CD8- phenotype pattern. CD3 and CD5 were expressed in all MTNKL. CD7 was absent in three cases of T-LGL. TCRα/β was performed in three cases of T-LGL and was positive in all. TCRα/β was also seen in both the cases of T-PLL small variant. However, TCRα/β was seen in the single case of PCGDTCL. Conclusion : Mature nodal T/NK cell neoplasms are rare and MTNKL presenting as leukemia are even rarer. There is an overlap between the immunophenotypic profiles of different MTNKL subtypes and elaborate T/NK cell panels are required for their evaluation.

  11. Effect of drug-radiation order on stem cell response in Rauscher leukemia

    International Nuclear Information System (INIS)

    The authors previously reported on the effect of fractionated TB1 plus chemotherapy on normal endogenous hematopoietic stem cell (ECFU-S) survival in a mouse mode. They have now extended these studies to a leukemic mouse model. Using Rauscher virus, leukemia was induced in female SJL/J mice. Fourteen days later they were put onto therapy regimes involving fractionated TBI plus cyclophosphamide (CY) and cytosine arabinoside (Ara-C). The effects of varying the order of the drugs or the drugs plus TBI while keeping the total doses the same were then evaluated. The results indicated both the order of drug administration, as well as the fractionation versus non-fractionation of the TBI could significantly influence ECFU-S survival. For instance, when CY administration preceded that of Ara-C, followed by a single dose of 9.5 Gy at the end of the therapy protocol, the ECFU-S survival was twice as great as when Ara-C was administered first. Likewise, when the TBI was administered as a split dose, 1 Gy before the drugs and 8.5 Gy afterwards, the ECFU-S survival was 5 times as great when CY was the first drug as when Ara-C was giver first. These results suggest that not only fractionation of the TBI, but also the order in which the chemotherapy drugs are given can critically affect the level of stem cell survival in leukemic animals

  12. Treatment of hairy-cell leukemia with chemoradiotherapy and identical-twin bone-marrow transplantation

    International Nuclear Information System (INIS)

    A patient with progressive hairy-cell leukemia and a normal genetically identical twin presented an opportunity to determine the sensitivity of this disease to high-dose alkylating-agent chemotherapy and total-body irradiation, since the marrow aplasia induced could potentially be overcome by reconstitution with normal marrow stem cells from the twin. After such therapy the patient rapidly recovered normal marrow function with no evidence of infiltrating hairy cells; he is still in complete remission four years after transplantation. In contrast to other patients with this disorder, he has had no predisposition to infections since transplantation. These results demonstrate that hairy-cell leukemia is sensitive to high-dose cytotoxic therapy and is not associated with any microenvironmental abnormalities that prevent repopulation with normal stem cells. Thus, high-dose chemoradiotherapy followed by bone-marrow transplantation is an effective and potentially curative therapy for hairy-cell leukemia

  13. 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...

  14. Prdm14 initiates lymphoblastic leukemia after expanding a population of cells resembling common lymphoid progenitors

    OpenAIRE

    E J Dettman; Simko, Stephen J.; Ayanga, Bernard; Carofino, Brandi; Margolin, Judith; Morse, Herbert C.; Justice, Monica J.

    2011-01-01

    Understanding the heterogeneous genetic mechanisms of tumor initiation in lymphoid leukemias (LL) will lead to improvements in prognostic classification and treatment regimens. In previous studies of mouse leukemias, we showed that retroviral insertion at the Evi32 locus leads to increased expression of Prdm14, a pluripotency gene implicated in the self-renewal capacity of embryonic stem cells and the early stages of breast cancer. Here we show that PRDM14 is also overexpressed in ~25% of hum...

  15. BLV-CoCoMo-qPCR: Quantitation of bovine leukemia virus proviral load using the CoCoMo algorithm

    Directory of Open Access Journals (Sweden)

    Matoba Kazuhiro

    2010-11-01

    Full Text Available Abstract Background Bovine leukemia virus (BLV is closely related to human T-cell leukemia virus (HTLV and is the etiological agent of enzootic bovine leukosis, a disease characterized by a highly extended course that often involves persistent lymphocytosis and culminates in B-cell lymphomas. BLV provirus remains integrated in cellular genomes, even in the absence of detectable BLV antibodies. Therefore, to understand the mechanism of BLV-induced leukemogenesis and carry out the selection of BLV-infected animals, a detailed evaluation of changes in proviral load throughout the course of disease in BLV-infected cattle is required. The aim of this study was to develop a new quantitative real-time polymerase chain reaction (PCR method using Coordination of Common Motifs (CoCoMo primers to measure the proviral load of known and novel BLV variants in clinical animals. Results Degenerate primers were designed from 52 individual BLV long terminal repeat (LTR sequences identified from 356 BLV sequences in GenBank using the CoCoMo algorithm, which has been developed specifically for the detection of multiple virus species. Among 72 primer sets from 49 candidate primers, the most specific primer set was selected for detection of BLV LTR by melting curve analysis after real-time PCR amplification. An internal BLV TaqMan probe was used to enhance the specificity and sensitivity of the assay, and a parallel amplification of a single-copy host gene (the bovine leukocyte antigen DRA gene was used to normalize genomic DNA. The assay is highly specific, sensitive, quantitative and reproducible, and was able to detect BLV in a number of samples that were negative using the previously developed nested PCR assay. The assay was also highly effective in detecting BLV in cattle from a range of international locations. Finally, this assay enabled us to demonstrate that proviral load correlates not only with BLV infection capacity as assessed by syncytium formation, but

  16. Acute 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, however, the bone marrow produces abnormal white blood ...

  17. Acute 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, however, the bone marrow produces abnormal white blood ...

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

    Directory of Open Access Journals (Sweden)

    Ramyar Asghar

    2009-06-01

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

  19. Childhood Leukemia

    Science.gov (United States)

    ... cells. It is the most common type of childhood cancer. Your blood cells form in your bone ... in the bones or joints Risk factors for childhood leukemia include having a brother or sister with ...

  20. Structural criteria for regulation of membrane fusion and virion incorporation by the murine leukemia virus TM cytoplasmic domain

    International Nuclear Information System (INIS)

    The cytoplasmic domains of viral glycoproteins influence the trafficking and subcellular localization of the glycoproteins and their incorporation into virions. They also promote correct virus morphology and viral budding. The cytoplasmic domains of murine-leukemia-virus envelope-protein TM subunits regulate membrane fusion. During virion maturation the carboxy-terminal 16 amino acid residues of the TM protein are removed by the retroviral protease. Deletion of these residues activates envelope-protein-mediated membrane fusion. Our quantitative analysis of the effects of Moloney murine leukemia virus TM mutations on envelope-protein function support the proposition that a trimeric coiled coil in the TM cytoplasmic domain inhibits fusion. The data demonstrate that cleavage of the TM cytoplasmic domain is not required for viral entry and provide evidence for a model in which fusogenic and nonfusogenic conformations of the envelope protein exists in an equilibrium that is regulated by the cytoplasmic domain. In addition, a conserved tyrosine residue in the TM cytoplasmic domain was shown to play an important role in envelope-protein incorporation into retroviral particles

  1. A human TRIM5alpha B30.2/SPRY domain mutant gains the ability to restrict and prematurely uncoat B-tropic murine leukemia virus.

    Science.gov (United States)

    Diaz-Griffero, Felipe; Perron, Michel; McGee-Estrada, Kathleen; Hanna, Robert; Maillard, Pierre V; Trono, Didier; Sodroski, Joseph

    2008-09-01

    Human TRIM5alpha restricts N-tropic murine leukemia virus (N-MLV) but not B-tropic MLV (B-MLV) infection. Here we study B30.2/SPRY domain mutants of human TRIM5alpha that acquire the ability to inhibit B-MLV infection prior to reverse transcription without losing the ability to restrict N-MLV infection. Remarkably, these mutants gain the ability to decrease the amount of particulate B-MLV capsids in the cytosol of infected cells. In addition, these mutants gain the ability to restrict SIV(mac) and HIV-2 infection. B-MLV and SIV(mac) infections were blocked by the mutant TRIM5alpha proteins prior to reverse transcription. Thus, the range of retroviruses restricted by human TRIM5alpha can be increased by changes in the B30.2/SPRY domain, which also result in the ability to cause premature uncoating of the restricted retroviral capsid. PMID:18586294

  2. 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

  3. Detection of an early adult T-cell leukemia-lymphoma clone in lymph nodes with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma involvement.

    Science.gov (United States)

    Tokunaga, Masahito; Yoshida, Noriaki; Nakano, Nobuaki; Kubota, Ayumu; Takeuchi, Shogo; Takatsuka, Yoshifusa; Seto, Masao; Utsunomiya, Atae

    2016-04-01

    A 58-year-old man was admitted to our hospital with systemic lymphadenopathy and was diagnosed with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALCL) by lymph node biopsy. Although he was a human T-cell leukemia virus type I (HTLV-1) carrier, Southern blot analysis of the lymph node did not show monoclonal integration of HTLV-1 provirus deoxyribonucleic acid (DNA). He achieved complete remission after chemotherapy and subsequently, autologous peripheral blood stem cell transplantation (auto-PBSCT) was performed. Fifteen months after the auto-PBSCT, abnormal lymphocytes in the peripheral blood gradually increased. Southern blot analysis revealed monoclonal integration of HTLV-1 provirus DNA and monoclonal rearrangement of TRB. He was diagnosed with chronic type adult T-cell leukemia-lymphoma (ATL), which immediately progressed to the acute type. He died of tumor progression despite intensive chemotherapy. We analyzed genomic alterations of the ALCL and ATL cells using array comparative genomic hybridization. We found that the genomic alteration pattern differed between the two diseases. T-cell receptor clonality analysis using polymerase chain reaction (PCR) showed that the T-cell clone of the ATL was present in the lymph nodes with ALCL involvement, but not in peripheral blood. This finding suggests that lymph nodes can serve as a niche for ATL development. PMID:26874918

  4. A rare case of plasma cell leukemia in a 35 year old

    Directory of Open Access Journals (Sweden)

    Rupal V Dosi

    2010-01-01

    Full Text Available Plasma cell leukemia is a rare, aggressive form of multiple myeloma. A 35-year-old male presented with backache, generalized weakness, and facial puffiness. His complete blood count showed anemia and a high WBC count with atypical cells on peripheral smear. Bone marrow examination showed more than 90% of atypical plasma cells, confirming a diagnosis of plasma cell leukemia. Patient also had azotemia, hypercalcemia, and hyperuricemia. The patient was started on chemotherapy along with supportive care. Patient improved dramatically and he was discharged on regular follow-up.

  5. Effect of DC-CIK cell on the proliferation, apoptosis and differentiation of leukemia cells

    Institute of Scientific and Technical Information of China (English)

    Hui-Qing Qu; Xiao-Sheng Zhou; Xiao-Long Zhou; Jian Wang

    2014-01-01

    Objective:To observe the effect of co-culture cytokine-induced killer cells(CIK) and homologous dendritic cells(DC) on the proliferative activity and phenotype change of theDC-CIK cell and the cell killing activity of leukemiaHL-60.Methods:50 mL cord blood sample was obtained from infants delivered by full term healthy woman and the cord blood mononuclear cells were isolated by density gradient centrifugation.Non-adherent cells were collectedfor the induction culture ofCIK, adherent cells were differentiated into matureDC; cultured matureDC was mixed with andCIK in the proportion of1:5 for12 d.Killing activity ofDC-CIK co-cultured cell on leukemiaHL-60 was detected byMTT assay.Results:Compared withCIKs, the co-culturedDC-CIKs presented a markedly higher proliferation and killing activity.Conclusions:Co-culture ofDC-CIK cells led to a significant increase of the proliferation and cytotoxicity of CIK.

  6. 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

  7. Synergistic effect of green tea EGCG treatment with gamma radiation in leukemia cell necrosis

    International Nuclear Information System (INIS)

    During cancer therapy, gamma-ray irradiation and treatment of anti-cancer chemicals destroy the normal cells as well as cancer cells. In this study, we investigated the effect of epigallocathechin-gallate (EGCG) extracted from green tea, which is known to have anti-cancer and anti-oxident activities, in order to find out the feasible method to protect the normal cells and to kill the cancer cells efficiently. We investigated the effect of EGCG on the leukemia cell growth and cell necrosis, especially when treated along with gamma radiation. The EGCG inhibited the leukemia cell, HL-60, growth at the appropriate concentration while it exhibited no influence on the normal cell growth. More significantly, it enhanced leukemia cell necrosis when its treatment was combined with gamma irradiation. Simultaneous treatment of EGCG and gamma radiation increased leukemia cell necrosis up to 35% compared with separate treatments. These results suggest that drinking of green tea or co-treatment of EGCG during gamma irradiation therapy may result in better prognosis through enhancement of the tumor cell necrosis and protection of the normal cells

  8. Risk factors associated with increased bovine leukemia virus proviral load in infected cattle in Japan from 2012 to 2014.

    Science.gov (United States)

    Ohno, Ayumu; Takeshima, Shin-nosuke; Matsumoto, Yuki; Aida, Yoko

    2015-12-01

    Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis, a malignant B cell lymphoma. BLV has spread worldwide and causes serious problems. After infection, the BLV genome is integrated into the host DNA and can be amplified during periods of latency. We previously designed degenerate primers using the Coordination of Common Motifs (CoCoMo) algorithm to establish a new quantitative real-time PCR method (BLV-CoCoMo-qPCR-2) of measuring the proviral load of both known and novel BLV variants. Here, we aimed to examine the correlation between proviral load and risk factors for BLV infection, such as breeding systems, parousity, and colostrum feeding. Blood and serum samples were collected from 83 BLV-positive farms in 22 prefectures of Japan, and the BLV proviral load and anti-BLV antibody levels were measured. BLV was detected in 73.3% (1039/1,417) of cattle by BLV-CoCoMo-qPCR-2 and the provirus was detected in 93 of 1039 antibody-negative samples. The results showed that the proviral load increased with progression of lymphocytosis. Next, the risk factors associated with increasing BLV infection rate were examined along with any association with proviral load. The proviral load was higher in cattle with lymphocytosis than in healthy cattle, and higher in multiparous cows than in nulliparous cows. Finally, proviral loads were higher in contact breeding systems than in non-contact breeding systems. Taken together, these findings may help to formulate a plan for eliminating BLV from contaminated farms. This is the first nationwide study to estimate BLV proviral load in Japanese cattle. PMID:26321160

  9. Distinct roles of enhancer nuclear factor 1 (NF1) sites in plasmacytoma and osteopetrosis induction by Akv1-99 murine leukemia virus

    International Nuclear Information System (INIS)

    Murine leukemia viruses (MLVs) can be lymphomagenic and bone pathogenic. In this work, the possible roles of two distinct proviral enhancer nuclear factor 1 (NF1) binding sites in osteopetrosis and tumor induction by B-lymphomagenic Akv1-99 MLV were investigated. Akv1-99 and mutants either with NF1 site 1, NF1 site 2 or both sites disrupted induced tumors (plasma cell proliferations by histopathology) with remarkably similar incidence and mean latency in inbred NMRI mice. Clonal immunoglobulin gene rearrangement detection, by Southern analysis, confirmed approximately half of the tumors induced by each virus to be plasmacytomas while the remaining lacked detectable clonally rearranged Ig genes and were considered polyclonal; a demonstration that enhancer NF1 sites are dispensable for plasmacytoma induction by Akv1-99. In contrast, X-ray analysis revealed significant differences in osteopetrosis induction by the four viruses strongly indicating that NF1 site 2 is critical for viral bone pathogenicity, whereas NF1 site 1 is neutral or moderately inhibitory. In conclusion, enhancer NF1 sites are major determinants of osteopetrosis induction by Akv1-99 without significant influence on viral oncogenicity

  10. Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity?

    Directory of Open Access Journals (Sweden)

    Elisa Dorantes-Acosta

    2012-01-01

    Full Text Available Acute leukemias are the most common cancer in childhood and characterized by the uncontrolled production of hematopoietic precursor cells of the lymphoid or myeloid series within the bone marrow. Even when a relatively high efficiency of therapeutic agents has increased the overall survival rates in the last years, factors such as cell lineage switching and the rise of mixed lineages at relapses often change the prognosis of the illness. During lineage switching, conversions from lymphoblastic leukemia to myeloid leukemia, or vice versa, are recorded. The central mechanisms involved in these phenomena remain undefined, but recent studies suggest that lineage commitment of plastic hematopoietic progenitors may be multidirectional and reversible upon specific signals provided by both intrinsic and environmental cues. In this paper, we focus on the current knowledge about cell heterogeneity and the lineage switch resulting from leukemic cells plasticity. A number of hypothetical mechanisms that may inspire changes in cell fate decisions are highlighted. Understanding the plasticity of leukemia initiating cells might be fundamental to unravel the pathogenesis of lineage switch in acute leukemias and will illuminate the importance of a flexible hematopoietic development.

  11. 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.

  12. DNA Damage, Cell Cycle Arrest, and Apoptosis Induction Caused by Lead in Human Leukemia Cells

    OpenAIRE

    Yedjou, Clement G.; Tchounwou, Hervey M.; Tchounwou, Paul B.

    2015-01-01

    In recent years, the industrial use of lead has been significantly reduced from paints and ceramic products, caulking, and pipe solder. Despite this progress, lead exposure continues to be a significant public health concern. The main goal of this research was to determine the in vitro mechanisms of lead nitrate [Pb(NO3)2] to induce DNA damage, apoptosis, and cell cycle arrest in human leukemia (HL-60) cells. To reach our goal, HL-60 cells were treated with different concentrations of Pb(NO3)...

  13. Effects of tacrolimus on infection of Friend murine leukemia virus to Fv-4 gene heterozygous mice

    Institute of Scientific and Technical Information of China (English)

    Feng-min ZHANG; Bao-feng YANG; Hong-xi GU; Xiao-bei CHEN; Zhao-hua ZHONG; Zhi CHENG

    2004-01-01

    AIM: To investigate the effect of tacrolimus (FK506) on the infection of Friend murine leukemia virus (Friend MuLV) in vivo. METHODS: Three kinds of mice were used including Friend MuLV-sensitive BALB/c mice, Friend MuLV-resistant Fv-4 gene-homozygous mice (Fv-4 mice), and Friend MuLV-resistant Fv-4 gene-heterozygous mice (Fl mice). Tacrolimus was administrated ip to those mice in every 2 d. Those treated mice were inoculated ip with Friend MuLV once on d 3. The symptoms and viral proliferations in those mice were observed to recognize the Friend MuLV infection. The expression and genotype of Fv-4 gene that resistant against the infection of Friend MuLV were analyzed to confirm the genomic background and related mechanism of the resistance. RESULTS:BALB/c mice and Fl mice, but not Fv-4 mice, appeared obvious early death, spleenomegaly, and viral proliferation after both treatments of viral inoculation and tacrolimus administration, whereas the expression and genotype of Fv-4 gene was not changed in F1 mice and Fv-4 mice with treatment of tacrolimus. Compared to the virusinoculated control, the Friend MuLV-sensitivity of tacrolimus-treated BALB/c mice and the Friend MuLV-resistance of tacrolimus-treated Fv-4 mice were the same as the controls, but only Fl mice became the symptoms and viral proliferation after both treatments. It suggested the Friend MuLV-resistant Fl mice could be converted to be Friend MuLV-sensitive by treatment of tacrolimus, and this conversion was not depended on the expression and genotype of Fv-4 gene. CONCLUSION: Tacrolimus could not inhibit the infection of Friend MuLV in all mice, furthermore,it could enhance the infection of Friend MuLV in F1 mice. The enhancement may be related to the immunosuppressive effect of tacrolimus.

  14. Differential Pathogenicity of Two Feline Leukemia Virus Subgroup A Molecular Clones, pFRA and pF6A

    OpenAIRE

    Phipps, Andrew J.; Chen, Hang; Hayes, Kathleen A.; Roy-Burman, Pradip; Mathes, Lawrence E.

    2000-01-01

    F6A, a molecular clone of subgroup A feline leukemia virus (FeLV) is considered to be highly infectious but weakly pathogenic. In recent studies with a closely related subgroup A molecular clone, FRA, we demonstrated high pathogenicity and a strong propensity to undergo recombination with endogenous FeLV (enFeLV), leading to a high frequency of transition from subgroup A to A/B. The present study was undertaken to identify mechanisms of FeLV pathogenesis that might become evident by comparing...

  15. Specific Cleavages by RNase H Facilitate Initiation of Plus-Strand RNA Synthesis by Moloney Murine Leukemia Virus

    OpenAIRE

    Schultz, Sharon J.; Zhang, Miaohua; Champoux, James J.

    2003-01-01

    Successful generation, extension, and removal of the plus-strand primer is integral to reverse transcription. For Moloney murine leukemia virus, primer removal at the RNA/DNA junction leaves the 3′ terminus of the plus-strand primer abutting the downstream plus-strand DNA, but this 3′ terminus is not efficiently reutilized for another round of extension. The RNase H cleavage to create the plus-strand primer might similarly result in the 3′ terminus of this primer abutting downstream RNA, yet ...

  16. Development of an enzyme-linked immunosorbent assay based on the murine leukemia virus p30 Capsid protein

    OpenAIRE

    Wu, Dai-Tze; Aiyer, Sriram; Villanueva, Rodrigo A.; Roth, Monica J

    2013-01-01

    Retroviral vectors derived from the murine leukemia virus (MuLV) are widely used as the starting material in the development of vectors for gene therapy and critical in answering questions relating to viral pathogenesis. The p30 capsid (CA) is the major viral core protein and an internal group antigen in MuLV. In this study, an enzyme-linked immunosorbent assay (ELISA) was developed for quantitation of MuLV infectious particles with p30 CA core antigen protein. The ELISA was...

  17. Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia

    OpenAIRE

    Brandao, L N; Winges, A; Christoph, S; Sather, S; Migdall-Wilson, J; Schlegel, J.; McGranahan, A; Gao, D.; Liang, X; DeRyckere, D; Graham, D K

    2013-01-01

    Pediatric leukemia survival rates have improved dramatically over the past decades. However, current treatment protocols are still largely ineffective in cases of relapsed leukemia and are associated with a significant rate of chronic health conditions. Thus, there is a continued need for new therapeutic options. Here, we show that mer receptor tyrosine kinase (MerTK) was abnormally expressed in approximately one half of pediatric T-cell leukemia patient samples and T-cell acute lymphoblastic...

  18. Hypergranular precursor B-cell acute lymphoblastic leukemia in a 16-year-old boy

    Directory of Open Access Journals (Sweden)

    Tembhare Prashant

    2009-07-01

    Full Text Available Presence of cytoplasmic granules in the blasts is a well known feature of myeloid leukemia. ALL presenting with the numerous cytoplasmic granules in blasts is a rarity and may be misdiagnosed as acute myeloid leukemia. We describe a rare case of hypergranular precursor B-cell acute lymphoblastic leukemia (ALL in an adolescent male expressing CD10, CD19, CytoCD22, CD34, as well as CD13 and CD117. The blasts were cytochemically negative for myeloperoxidase (MPO, and acid phosphatase (ACP but were positive for non-specific esterase (NSE. In centers where immunophenotypic panel is usually decided on the basis of morphology with limited antibodies may result in an erroneous typing of such rare diseases. Hence it is important to be aware of this rare entity and to confirm the lineage of acute leukemia by using a comprehensive panel of antibodies for immunophenotypic analysis.

  19. Inverse relationship of tumors and mononuclear cell leukemia infiltration in the lungs of F344 rats

    Energy Technology Data Exchange (ETDEWEB)

    Lundgren, D.L.; Griffith, W.C.; Hahn, F.F.

    1995-12-01

    In 1970 and F344 rat, along with the B6C3F{sub 1} mouse, were selected as the standard rodents for the National Cancer Institute Carcinogenic Bioassay program for studies of potentially carcinogenic chemicals. The F344 rat has also been used in a variety of other carcinogenesis studies, including numerous studies at ITRI. A major concern to be considered in evaluating carcinogenic bioassay studies using the F344 rat is the relatively high background incidence of mononuclear cell leukemia (MCL) (also referred to as large granular lymphocytic leukemia, Fischer rat leukemia, or monocytic leukemia). Incidences of MCL ranging from 10 to 72% in male F344 rats to 6 to 31% in female F344 rats have been reported. Gaining the understanding of the mechanisms involved in the negative correlations noted should enhance our understanding of the mechanisms involved in the development of lung cancer.

  20. Mouse Siglec-1 Mediates trans-Infection of Surface-bound Murine Leukemia Virus in a Sialic Acid N-Acyl Side Chain-dependent Manner.

    Science.gov (United States)

    Erikson, Elina; Wratil, Paul R; Frank, Martin; Ambiel, Ina; Pahnke, Katharina; Pino, Maria; Azadi, Parastoo; Izquierdo-Useros, Nuria; Martinez-Picado, Javier; Meier, Chris; Schnaar, Ronald L; Crocker, Paul R; Reutter, Werner; Keppler, Oliver T

    2015-11-01

    Siglec-1 (sialoadhesin, CD169) is a surface receptor on human cells that mediates trans-enhancement of HIV-1 infection through recognition of sialic acid moieties in virus membrane gangliosides. Here, we demonstrate that mouse Siglec-1, expressed on the surface of primary macrophages in an interferon-α-responsive manner, captures murine leukemia virus (MLV) particles and mediates their transfer to proliferating lymphocytes. The MLV infection of primary B-cells was markedly more efficient than that of primary T-cells. The major structural protein of MLV particles, Gag, frequently co-localized with Siglec-1, and trans-infection, primarily of surface-bound MLV particles, efficiently occurred. To explore the role of sialic acid for MLV trans-infection at a submolecular level, we analyzed the potential of six sialic acid precursor analogs to modulate the sialylated ganglioside-dependent interaction of MLV particles with Siglec-1. Biosynthetically engineered sialic acids were detected in both the glycolipid and glycoprotein fractions of MLV producer cells. MLV released from cells carrying N-acyl-modified sialic acids displayed strikingly different capacities for Siglec-1-mediated capture and trans-infection; N-butanoyl, N-isobutanoyl, N-glycolyl, or N-pentanoyl side chain modifications resulted in up to 92 and 80% reduction of virus particle capture and trans-infection, respectively, whereas N-propanoyl or N-cyclopropylcarbamyl side chains had no effect. In agreement with these functional analyses, molecular modeling indicated reduced binding affinities for non-functional N-acyl modifications. Thus, Siglec-1 is a key receptor for macrophage/lymphocyte trans-infection of surface-bound virions, and the N-acyl side chain of sialic acid is a critical determinant for the Siglec-1/MLV interaction. PMID:26370074

  1. Neural stem cells attacked by Zika virus.

    Science.gov (United States)

    Nguyen, Ha Nam; Qian, Xuyu; Song, Hongjun; Ming, Guo-Li

    2016-07-01

    The current outbreak of Zika virus-associated diseases in South America and its threat to spread to other parts of the world has emerged as a global health emergency. Insights from cell and animal models to understand how Zika virus causes severe birth defects may lead to treatments and prevention of these diseases. PMID:27283801

  2. 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...

  3. CD52 expression in T-cell large granular lymphocyte leukemia--implications for treatment with alemtuzumab.

    Science.gov (United States)

    Osuji, N; Del Giudice, I; Matutes, E; Morilla, A; Owusu-Ankomah, K; Morilla, R; Dunlop, A; Catovksy, D

    2005-05-01

    Few reports on the successful treatment of T-cell large granular lymphocyte (LGL) leukemia with the humanized anti-CD52 monoclonal antibody alemtuzumab are emerging in the literature. The expression of CD52 by LGLs has not been previously investigated. Using semi-quantitative 2- and 3-color flow cytometry, we documented the expression of CD52 in 100% of abnormal cells in T-cell LGL leukemia (n = 11) and natural killer (NK) cell LGL leukemia (n = 2), and showed no significant difference in CD52 expression between T-cell prolymphocytic leukemia (PLL) and T-cell LGL leukemia. Higher CD52 expression has been noted in responders to alemtuzumab in T-cell PLL and in chronic lymphocytic leukemia (CLL), a B-cell disorder. The strong and consistent expression of CD52 shown here highlights the potential role of alemtuzumab in the treatment of refractory T-cell LGL leukemia and possibly aggressive NK cell leukemia. PMID:16019510

  4. PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation.

    Science.gov (United States)

    Kong, Y; Zhang, J; Claxton, D F; Ehmann, W C; Rybka, W B; Zhu, L; Zeng, H; Schell, T D; Zheng, H

    2015-01-01

    Prognosis of leukemia relapse post allogeneic stem cell transplantation (alloSCT) is poor and effective new treatments are urgently needed. T cells are pivotal in eradicating leukemia through a graft versus leukemia (GVL) effect and leukemia relapse is considered a failure of GVL. T-cell exhaustion is a state of T-cell dysfunction mediated by inhibitory molecules including programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3). To evaluate whether T-cell exhaustion and inhibitory pathways are involved in leukemia relapse post alloSCT, we performed phenotypic and functional studies on T cells from peripheral blood of acute myeloid leukemia patients receiving alloSCT. Here we report that PD-1(hi)TIM-3(+) cells are strongly associated with leukemia relapse post transplantation. Consistent with exhaustion, PD-1(hi)TIM-3(+) T cells are functionally deficient manifested by reduced production of interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In addition, these cells demonstrate a phenotype consistent with exhausted antigen-experienced T cells by losing TN and TEMRA subsets. Importantly, increase of PD-1(hi)TIM-3(+) cells occurs before clinical diagnosis of leukemia relapse, suggesting their predictive value. Results of our study provide an early diagnostic approach and a therapeutic target for leukemia relapse post transplantation. PMID:26230954

  5. PD-1hiTIM-3+ T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation

    International Nuclear Information System (INIS)

    Prognosis of leukemia relapse post allogeneic stem cell transplantation (alloSCT) is poor and effective new treatments are urgently needed. T cells are pivotal in eradicating leukemia through a graft versus leukemia (GVL) effect and leukemia relapse is considered a failure of GVL. T-cell exhaustion is a state of T-cell dysfunction mediated by inhibitory molecules including programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3). To evaluate whether T-cell exhaustion and inhibitory pathways are involved in leukemia relapse post alloSCT, we performed phenotypic and functional studies on T cells from peripheral blood of acute myeloid leukemia patients receiving alloSCT. Here we report that PD-1hiTIM-3+ cells are strongly associated with leukemia relapse post transplantation. Consistent with exhaustion, PD-1hiTIM-3+ T cells are functionally deficient manifested by reduced production of interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In addition, these cells demonstrate a phenotype consistent with exhausted antigen-experienced T cells by losing TN and TEMRA subsets. Importantly, increase of PD-1hiTIM-3+ cells occurs before clinical diagnosis of leukemia relapse, suggesting their predictive value. Results of our study provide an early diagnostic approach and a therapeutic target for leukemia relapse post transplantation

  6. Selection of functional tRNA primers and primer binding site sequences from a retroviral combinatorial library: identification of new functional tRNA primers in murine leukemia virus replication

    DEFF Research Database (Denmark)

    Lund, Anders Henrik; Duch, M; Pedersen, F S

    2000-01-01

    Retroviral reverse transcription is initiated from a cellular tRNA molecule and all known exogenous isolates of murine leukemia virus utilise a tRNA(Pro)molecule. While several studies suggest flexibility in murine leukemia virus primer utilisation, studies on human immunodeficiency virus and avian...... retro-viruses have revealed evidence of molecular adapt-ation towards the specific tRNA isoacceptor used as replication primer. In this study, murine leukemia virus tRNA utilisation is investigated by in vivo screening of a retroviral vector combinatorial library with randomised primer binding sites....... While most of the selected primer binding sites are complementary to the 3'-end of tRNA((Pro)), we also retrieved PBS sequences matching four other tRNA molecules and demonstrate that Akv murine leukemia virus vectors may efficiently replicate using tRNA(Arg(CCU)), tRNA(Phe(GAA))and a hitherto unknown...

  7. Tumor necrosis factor-alpha (TNFα) gene polymorphism and expression of membrane-bound TNFα protein on CD11b+ and IgM+ cells in cows naturally infected with bovine leukemia virus.

    Science.gov (United States)

    Bojarojć-Nosowicz, B; Kaczmarczyk, E; Stachura, A; Kubińska, M

    2015-01-01

    The aim of this study was to determine whether SNP at position -824 (promoter region) of the TNFα gene significantly differentiates the size of IgM+, CD5+ and CD11b+ cell subpopulations and affects the expression of membrane-bound TNFα protein (mTNFα) on these cells and their susceptibility to BLV infections. In this study, significant differences were determined for the first time between TNFα genotypes and the percentage of cells with the CD11b+TNFα+p24+ immunophenotype. Furthermore, greater expansion of lymphocytes with the IgM+TNFα+p24+ immunophenotype was reported in cows with the G/G genotype than in A/A homozygotes. Cells with the above immunophenotype were more frequently observed in cows with persistent leukocytosis than in aleukemic cattle. Our results suggest that polymorphism of the TNFα-824 A>G gene and mTNFα protein expression play an important role in the pathogenesis of enzootic bovine leukosis. PMID:26618585

  8. Oral Manifestations of T-Cell Large Granular Lymphocytic Leukemia: a Case Report

    Directory of Open Access Journals (Sweden)

    Ioanna-Eirini Arvanitidou

    2011-06-01

    Full Text Available Background: T-cell large granular lymphocytic (T-LGL leukemia is a rare, chronic, often indolent lymphoproliferative disorder of mature T cells (CD3+. Severe neutropenia and other cytopenias are common features in patients with T-LGL leukemia and may cause infections, thus representing a major cause of morbidity in this disease. Immunosuppressive therapy with low-dose regimes of methotrexate, cyclophosphamide, corticosteroids or cyclosporine A is the treatment of choice. Amongst the variety of T-LGL leukemia complications, oral manifestations such as ulcers have been rarely reported. The purpose of this paper is to report a case of T-cell large granular lymphocyte leukemia with oral manifestations and to discuss their pathogenesis and management.Methods: In the present case, a 65 year old female with a two-month history of diagnosed T-LGL leukemia presented with oral lesions, including ulcerations on the ventral tongue and soft palate as well as swollen, erythematous and ulcerated gingiva. The patient was under treatment with methotrexate, granulocyte colony-stimulating factor (G-CSF and erythropoietin.Results: Considering patients’ medical history and clinical appearance of the lesions, a clinical diagnosis of a neutropenic ulcer of the tongue was established. The oral lesions resolved after treatment with antibiotics, topical steroids and antiseptics combined with improvement of the hematological condition. The pertinent literature related to T-LGL leukemia ethiopathology, diagnostics and treatment was discussed.Conclusions: Although rare, T-cell large granular lymphocytic leukemia should be included in the list of lymphoproliferative disorders, which may present with oral manifestations as a result of the disease and its treatment complications.

  9. Atomic resolution structure of Moloney murine leukemia virus matrix protein and its relationship to other retroviral matrix proteins.

    Science.gov (United States)

    Riffel, Nico; Harlos, Karl; Iourin, Oleg; Rao, Zihe; Kingsman, Alan; Stuart, David; Fry, Elizabeth

    2002-12-01

    Matrix proteins associated with the viral membrane are important in the formation of the viral particle and in virus maturation. The 1.0 A crystal structure of the ecotropic Gammaretrovirus Moloney murine leukemia virus (M-MuLV) matrix protein reveals the conserved topology of other retroviral matrix proteins, despite undetectable sequence similarity. The N terminus (normally myristylated) is exposed and adjacent to a basic surface patch, features likely to contribute to membrane binding. The four proteins in the asymmetric unit make varied contacts. The M-MuLV matrix structure is intermediate, between those of the lentiviruses and other retroviruses. The protein fold appears to be maintained, in part, by the conservation of side chain packing, which may provide a useful tool for searching for weak distant similarities in proteins. PMID:12467570

  10. Cell Culture for Production of Insecticidal Viruses.

    Science.gov (United States)

    Reid, Steven; Chan, Leslie C L; Matindoost, Leila; Pushparajan, Charlotte; Visnovsky, Gabriel

    2016-01-01

    While large-scale culture of insect cells will need to be conducted using bioreactors up to 10,000 l scale, many of the main challenges for cell culture-based production of insecticidal viruses can be studied using small-scale (20-500 ml) shaker/spinner flasks, either in free suspension or using microcarrier-based systems. These challenges still relate to the development of appropriate cell lines, stability of virus strains in culture, enhancing virus yields per cell, and the development of serum-free media and feeds for the desired production systems. Hence this chapter presents mainly the methods required to work with and analyze effectively insect cell systems using small-scale cultures. Outlined are procedures for quantifying cells and virus and for establishing frozen cells and virus stocks. The approach for maintaining cell cultures and the multiplicity of infection (MOI) and time of infection (TOI) parameters that should be considered for conducting infections are discussed.The methods described relate, in particular, to the suspension culture of Helicoverpa zea and Spodoptera frugiperda cell lines to produce the baculoviruses Helicoverpa armigera nucleopolyhedrovirus, HearNPV, and Anticarsia gemmatalis multicapsid nucleopolyhedrovirus, AgMNPV, respectively, and the production of the nonoccluded Oryctes nudivirus, OrNV, using an adherent coleopteran cell line. PMID:27565495

  11. Antiproliferative effect of rapamycin on human T-cell leukemia cell line Jurkat by cell cycle arrest and telomerase inhibition

    Institute of Scientific and Technical Information of China (English)

    Yan-min ZHAO; Qian ZHOU; Yun XU; Xiao-yu LAI; He HUANG

    2008-01-01

    Aim:To examine the ability of rapamycin to suppress growth and regulate telomerase activity in the human T-cell leukemia cell line Jurkat. Methods:Cell proliferation was assessed after exposure to rapamycin by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were determined by flow cytometry. The proteins important for cell cycle progres-sion and Akt/mammalian target of rapamycin signaling cascade were assessed by Western blotting. Telomerase activity was quantified by telomeric repeat amplication protocol assay. The human telomerase reverse transcriptase (hTERT) mRNA levels were determined by semi-quantitative RT-PCR. Results:Rapamycin inhibited the proliferation of Jurkat, induced G1 phase arrest, unregulated the pro-tein level of p21 as well as p27, and downregulated cyclinD3, phospho-p70s6k, and phospho-s6, but had no effect on apoptosis. Treatment with rapamycin reduced telomerase activity, and reduced hTERT mRNA and protein expression. Conclusion:Rapamycin displayed a potent antileukemic effect in the human T-cell leukemia cell line by inhibition of cell proliferation through G1 cell cycle arrest and also through the suppression of telomerase activity, suggesting that rapamycin may have potential clinical implications in the treatment of some leukemias.

  12. Triptolide induces apoptotic cell death of human cholangiocarcinoma cells through inhibition of myeloid cell leukemia-1

    International Nuclear Information System (INIS)

    Cholangiocarcinoma (CCA), a devastating neoplasm, is highly resistant to current chemotherapies. CCA cells frequently overexpress the antiapoptotic protein myeloid cell leukemia-1(Mcl-1), which is responsible for its extraordinary ability to evade cell death. Triptolide, a bioactive ingredient extracted from Chinese medicinal plant, has been shown to inhibit cell proliferation and induce apoptosis in several cancers. CCK-8 assay was performed to detect cell survival rate in vitro. DAPI staining and Flow cytometry were used to analyze apoptosis. Western blot was performed to determine the expression levels of caspase-3, caspase-7, caspase-9, PARP, and Mcl-1. Quantitative real-time PCR and immunofluorescence were used to detect the expression levels of Mcl-1. The nude mice xenograft model was used to evaluate the antitumor effect of triptolide in vivo. Triptolide reduced cell viability in cholangiocarcinoma cell lines in a dose- and time-dependent manner, with IC50 values of 12.6 ± 0.6 nM, 20.5 ± 4.2 nM, and 18.5 ± 0.7 nM at 48 h for HuCCT1, QBC939, and FRH0201 respectively. Triptolide induced apoptosis in CCA cell lines in part through mitochondrial pathway. Using quantitative real-time PCR, western blot and immunofluorescence, we have shown that triptolide downregulates Mcl-1 mRNA and protein levels. Furthermore, triptolide inhibited the CCA growth in vivo. Triptolide has profound antitumor effect on CCA, probably by inducing apoptosis through inhibition of Mcl-1. Triptolide would be a promising therapeutic agent for CCA

  13. Identification of a novel SEPT9-ABL1 fusion gene in a patient with T-cell prolymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Rikio Suzuki

    2014-01-01

    Full Text Available T-cell prolymphocytic leukemia (T-PLL, a rare type of peripheral T-cell leukemia, is characterized by marked splenomegaly with rapidly progressive lymphocytosis and a poor prognosis. Nine kinds of ABL1 chimeric genes have been identified in various kinds of hematological malignancies, such as chronic myeloid leukemia and B- or T-lymphoblastic leukemia. However, there have been no reports describing T-PLL cases with ABL1 rearrangements. We herein report a case of T-PLL with a novel SEPT9-ABL1 fusion gene which induced strong resistance to tyrosine kinase inhibitors such as imatinib and dasatinib.

  14. Concise Review: Preleukemic Stem Cells: Molecular Biology and Clinical Implications of the Precursors to Leukemia Stem Cells

    OpenAIRE

    Pandolfi, Ashley; Barreyro, Laura; Steidl, Ulrich

    2013-01-01

    Despite the established use of poly-chemotherapy, relapse continues to be the most common cause of death in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The therapeutic elimination of all leukemia stem cells (LSC) and pre-LSC will be essential for achieving lasting cures. This article reviews recent and ongoing advances in understanding the roles of pre-LSC, and the aberrations that lead to pre-LSC formation and subsequent LSC transformation.

  15. Radiation exposure as a possible etiologic factor in hairy cell leukemia (leukemic reticuloendotheliosis).

    Science.gov (United States)

    Stewart, D J; Keating, M J

    1980-10-01

    The frequency of prior occupational, accidental, or therapeutic radiation exposure was significantly higher for hairy cell leukemia patients than for a control group of solid tumor patients (8/23 vs. 4/56, P risk of radiation exposure such as chemist, engineer, physicist, and health care facility worker (7/23 vs. 4/56, P < 0.01). The observation that the incidence of thyroid disorders among hairy cell leukemia patients was also unusually high (5/23 vs. 2/56, P < 0.05) was interpreted as further indirect evidence of excessive radiation exposure. It appears that radiation exposure may be an important contribution factor in the development of some case of hairy cell leukemia. PMID:7417955

  16. Signal transduction pathways and transcription factors triggered by arsenic trioxide in leukemia cells

    International Nuclear Information System (INIS)

    Arsenic trioxide (As2O3) is widely used to treat acute promyelocytic leukemia (APL). Several lines of evidence have indicated that As2O3 affects signal transduction and transactivation of transcription factors, resulting in the stimulation of apoptosis in leukemia cells, because some transcription factors are reported to associate with the redox condition of the cells, and arsenicals cause oxidative stress. Thus, the disturbance and activation of the cellular signaling pathway and transcription factors due to reactive oxygen species (ROS) generation during arsenic exposure may explain the ability of As2O3 to induce a complete remission in relapsed APL patients. In this report, we review recent findings on ROS generation and alterations in signal transduction and in transactivation of transcription factors during As2O3 exposure in leukemia cells.

  17. Interleukin 1 as an autocrine growth factor for acute myeloid leukemia cells

    International Nuclear Information System (INIS)

    Production of interleukin 1 (IL-1) by leukemic cells was studied in 13 cases of acute myeloid leukemia. Intracytoplasmic immunofluorescence studies showed that the cells invariably contained the cytokine. Endogenous labeling studies demonstrated that acute myeloid leukemia cells produced either only the 33-kDa propeptide or both the propeptide and the 17-kDa mature form of IL-1β. The 33-kDa propeptide IL-1α was always produced but was less frequently released. Involvement of IL-1 in leukemic cell growth was investigated using two antibodies specific for IL-1 subtypes, which inhibited spontaneous cell proliferation in the six cases studied. After acid treatment of the cells, a surface receptor for IL-1 could be demonstrated, which mediated 125I-labeled IL-1-specific uptake by leukemic cells. Furthermore, recombinant IL-1α or IL-1β induced significant cell proliferation in 10 12 cases. The above findings were uncorrelated with the cytologic type (French-American-British classification) of leukemia. The studies suggest that IL-1 may act as an autocrine growth factor in most cases of acute myeloid leukemia

  18. Establishment and characterization of a human monocytoid leukemia cell line, CTV-1.

    Science.gov (United States)

    Chen, P; Chiu, C; Chiou, T; Maeda, S; Chiang, H; Tzeng, C; Sugiyama, T; Chiang, B N

    1984-08-01

    A new human monocytoid leukemic cell line, CTV-1, was established from a patient with relapsed acute monoblastic leukemia. The characteristics of this cell line were evaluated by morphologic and cytochemical analyses, electron-microscopy, chromosome study, surface marker analysis and a study of differentiation potential with tumor-promoting agents. PMID:6593267

  19. Using a Herd Profile to Determine Age-Specific Prevalence of Bovine Leukemia Virus in Michigan Dairy Herds

    Directory of Open Access Journals (Sweden)

    Ronald J. Erskine

    2012-01-01

    Full Text Available Enzootic bovine leukosis is a contagious disease of cattle caused by the retrovirus, bovine leukemia virus (BLV and is the most common cause of malignant neoplasm in cattle. In order to facilitate surveillance of this disease in dairy herds, we developed a method to combine ELISA of milk collected during routine production testing with a prescribed sampling of cows that is independent of the proportion of cows within each lactation. In 113 Michigan dairy herds, milk samples from ten cows in each of the 1st, 2nd, 3rd, and ≥4th lactations were analyzed for anti-Bovine Leukemia Virus (BLV antibodies by milk ELISA. For each herd, a BLV herd profile (BHP was calculated as the simple average of the percent of BLV-positive cows within each of the four lactation groups. The mean BHP for all herds was 32.8%, with means of 18.5, 28.8, 39.2, and 44.8% of 1st, 2nd, 3rd, and ≥4th lactation animals infected, respectively. In eight herds, we determined the correlation between the BHP, and true herd prevalence by testing the entire lactating herd (r=0.988,  P<0.0001. The BHP allows discrimination of lactation-specific BLV prevalence within a dairy herd, to help identify risk factors and management plans that may be important in transmission of BLV.

  20. Using a Herd Profile to Determine Age-Specific Prevalence of Bovine Leukemia Virus in Michigan Dairy Herds

    Science.gov (United States)

    Erskine, Ronald J.; Bartlett, Paul C.; Byrem, Todd M.; Render, Chelsea L.; Febvay, Catherine; Houseman, Jessica T.

    2012-01-01

    Enzootic bovine leukosis is a contagious disease of cattle caused by the retrovirus, bovine leukemia virus (BLV) and is the most common cause of malignant neoplasm in cattle. In order to facilitate surveillance of this disease in dairy herds, we developed a method to combine ELISA of milk collected during routine production testing with a prescribed sampling of cows that is independent of the proportion of cows within each lactation. In 113 Michigan dairy herds, milk samples from ten cows in each of the 1st, 2nd, 3rd, and ≥4th lactations were analyzed for anti-Bovine Leukemia Virus (BLV) antibodies by milk ELISA. For each herd, a BLV herd profile (BHP) was calculated as the simple average of the percent of BLV-positive cows within each of the four lactation groups. The mean BHP for all herds was 32.8%, with means of 18.5, 28.8, 39.2, and 44.8% of 1st, 2nd, 3rd, and ≥4th lactation animals infected, respectively. In eight herds, we determined the correlation between the BHP, and true herd prevalence by testing the entire lactating herd (r = 0.988, P < 0.0001). The BHP allows discrimination of lactation-specific BLV prevalence within a dairy herd, to help identify risk factors and management plans that may be important in transmission of BLV. PMID:22577607

  1. Acute myeloid leukemia arising from a donor derived premalignant hematopoietic clone: A possible mechanism for the origin of leukemia in donor cells

    Directory of Open Access Journals (Sweden)

    Mark A. Dickson

    2014-01-01

    Full Text Available During recent years, it has become increasingly evident that donor leukemia following allogeneic transplant may be more common then realized in the past. We identified five cases of potential donor leukemia cases during past five years. The precise mechanism of the origin of such leukemias, however, remains poorly defined. In this short communication, we report a well documented case of donor-derived de novo acute myeloid leukemia (AML that developed fourteen years after allogeneic stem cell transplantation for treatment induced AML for his primary malignancy Immunoblastic lymphoma. This case allows us to postulate a possible mechanism of the origin of donor leukemia. The de novo AML clone contained a distinct cytogenetic abnormality, trisomy 11, which was simultaneously detected in preserved peripheral blood obtained at the time of transplantation as well as in the current bone marrow from an otherwise clinically and phenotypically normal donor. The findings from this unique case, provides insight into the process of leukemogenesis, and suggests that the sequence of events leading to leukemogenesis in this patient involved the senescence/apoptosis of normal donor hematopoietic cells due to telomere shortening resulting in the selective proliferation and transformation of this clone with MLL (mixed-lineage leukemia gene amplification.

  2. Radioinduced leukemia. An introduction to the study of experimental leukemia in mice

    International Nuclear Information System (INIS)

    This thesis attempts to gain insight into any mechanisms involved in the onset of irradiation-induced leukemia in mice, then to show up the presence of a virus in the same animals. Concerning the mechanisms of radio-induced leukemias the pathogenic factors according to Kaplan are analysed: role of the thymus and cell mutation theory; lymphoid leukemias of extra-thymic origin; leukemogenesis co-factor; inhibiting action of the bone narrow. Evidence of the virus in mice was obtained by the use of electron microscopy, by inoculation. The contribution of experimental leukemia research is analysed, especially as it affects the therapeutic aspect. It is shown that in spite of setbacks in the most recent research on man, therapeutic trials on animals should be viewed from the angle of imminent human applications

  3. Dose- and Time-Dependent Response of Human Leukemia (HL-60 Cells to Arsenic Trioxide Treatment

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou

    2006-06-01

    Full Text Available The treatment of acute promyelocytic leukemia (APL has been based on the administration of all-trans retinoic acid plus anthracycline chemotherapy, which is very effective as first line therapy; however 25 to 30% of patients will relapse with their disease becoming refractory to conventional therapy. Recently, studies have shown arsenic trioxide to be effective in the treatment of acute promyelocytic leukemia. In this study, we used the human leukemia (HL-60 cell line as a model to evaluate the cytoxicity of arsenic trioxide based on the MTT assay. Data obtained from this assay indicated that arsenic trioxide significantly reduced the viability of HL-60 cells, showing LD50 values of 14.26 + 0.5μg/mL, 12.54 + 0.3μg/mL, and 6.4 + 0.6μg/mL upon 6, 12, and 24 hours of exposure, respectively; indicating a dose- and time-dependent response relationship. Findings from the present study indicate that arsenic trioxide is highly cytotoxic to human leukemia (HL-60 cells, supporting its use as an effective therapeutic agent in the management of acute promyelocytic leukemia.

  4. Molecular and clinical study on prevalence of feline herpesvirus type 1 and calicivirus in correlation with feline leukemia and immunodeficiency viruses

    OpenAIRE

    Najafi, Hamideh; Madadgar, Omid; Jamshidi, Shahram; Ghalyanchi Langeroudi, Arash; Darzi Lemraski, Mahdieh

    2014-01-01

    Upper respiratory tract diseases (URTD) are common clinical problem in cats worldwide. Feline calicivirus (FCV) and feline herpesvirus type 1 (FHV-1) are the main primary pathogens. Feline immunodeficiency virus (FIV) and Feline leukemia virus (FeLV) are also among the most common infectious diseases of cats which suppress the immunity. Oropharyngeal and conjunctival swabs and blood samples were taken from 16 cats with clinical signs of URTD and 26 clinically healthy cats. PCR and RT-PCR were...

  5. Recombination in the 5' leader of murine leukemia virus is accurate and influenced by sequence identity with a strong bias toward the kissing-loop dimerization region

    DEFF Research Database (Denmark)

    Mikkelsen, J G; Lund, Anders Henrik; Duch, M; Pedersen, F S

    1998-01-01

    Retroviral recombination occurs frequently during reverse transcription of the dimeric RNA genome. By a forced recombination approach based on the transduction of Akv murine leukemia virus vectors harboring a primer binding site knockout mutation and the entire 5' untranslated region, we studied ...... facilitate template switching. We discuss the putative role of the dimerization domain in the overall structure of the reverse-transcribed RNA dimer and note that related mechanisms of template switching may be found in remote RNA viruses....

  6. 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 ...

  7. Antibody to Heat Shock Protein 70 (HSP70) Inhibits Human T-Cell Lymphoptropic Virus Type I (HTLV-I) Production by Transformed Rabbit T-Cell Lines

    OpenAIRE

    Hanan Fallouh; Wahib Mahana

    2012-01-01

    Adult T cell leukemia is a fatal malignant transformation caused by the human T-cell lymphoptropic virus type I (HTLV-I). HTLV-I is only associated with the development of this disease in a small percentage of infected individuals. Using two rabbit transformed T-cell lines; RH/K30 (asymptomatic) and RH/K34 (leukemogenic), we have investigated the expression of heat shock proteins (HSP) 90 and 70 and the role of anti-HSPs antibodies on virus production. HSPs surface expression was higher on RH...

  8. Peripheral T-Cell lymphoma manifested as gingival enlargement in a patient with chronic lymphocytic leukemia

    OpenAIRE

    Buddula, Aravind; Assad, Daniel

    2011-01-01

    Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults and is associated with increased risk of malignancy. T-cell lymphoma associated with CLL has never been reported. The case report presents a unique case of peripheral T-cell lymphoma on the gingiva of a patient with CLL. A 66-year-old man with a history of CLL was referred to the Mayo Clinic, Department of Dental Specialties, for evaluation of swelling in the upper left posterior sextant. An intraoral examination...

  9. Trigeminal nerve involvement in T-cell acute lymphoblastic leukemia: value of MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Karadag, Demet; Karaguelle, Ayse Tuba; Erden, Ilhan; Erden, Ayse E-mail: erden@ada.net.tr

    2002-10-01

    A 30-year-old male with T-cell acute lymphoblastic leukemia presented with facial numbness. Neurological examination revealed paresthesia of the left trigeminal nerve. Cerebrospinal fluid (CSF) cytology showed no atypical cells. Gadolinium-enhanced magnetic resonance (MR) imaging demonstrated enlargement and enhancement of intracranial portions of the left trigeminal nerve. The abnormal MR imaging findings almost completely resolved after the chemotherapy. Gadolinium-enhanced MR imaging is not only a useful procedure for the early diagnosis of cranial nerve invasion by leukemia but it might be helpful to follow the changes after the treatment.

  10. Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission

    DEFF Research Database (Denmark)

    Nagler, Arnon; Rocha, Vanderson; Labopin, Myriam;

    2013-01-01

    Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable bioavailabil......Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable...

  11. Trigeminal nerve involvement in T-cell acute lymphoblastic leukemia: value of MR imaging

    International Nuclear Information System (INIS)

    A 30-year-old male with T-cell acute lymphoblastic leukemia presented with facial numbness. Neurological examination revealed paresthesia of the left trigeminal nerve. Cerebrospinal fluid (CSF) cytology showed no atypical cells. Gadolinium-enhanced magnetic resonance (MR) imaging demonstrated enlargement and enhancement of intracranial portions of the left trigeminal nerve. The abnormal MR imaging findings almost completely resolved after the chemotherapy. Gadolinium-enhanced MR imaging is not only a useful procedure for the early diagnosis of cranial nerve invasion by leukemia but it might be helpful to follow the changes after the treatment

  12. Acute Hepatitis A Induction of Precursor B-Cell Acute Lymphoblastic Leukemia: A Causal Relationship?

    OpenAIRE

    Senadhi, V.; Emuron, D.; R. Gupta

    2010-01-01

    Background Precursor B-cell acute lymphoblastic leukemia accounts for 2% of all lymphoid neoplasms in the United States and occurs most frequently in childhood, but can also occur in adults with a median age of 39 years. It is more commonly seen in males and in Caucasians. Case Report We present a case of a 51-year-old Caucasian female with the development of precursor B-cell acute lymphoblastic leukemia after suffering acute hepatitis A 4 weeks prior to her diagnosis. She presented with mala...

  13. A model with competition between the cell lines in leukemia under treatment

    Energy Technology Data Exchange (ETDEWEB)

    Halanay, A.; Cândea, D.; Rădulescu, R. [POLITEHNICA University of Bucharest Department of Mathematics and Informatics Splaiul Independentei 313 RO-060042 Bucharest (Romania)

    2014-12-10

    The evolution of leukemia is modeled with a delay differential equation model of four cell populations: two populations (healthy and leukemic) ) of stem-like cells involving a larger category consisting of proliferating stem and progenitor cells with self-renew capacity and two populations (healthy and leukemic) of mature cells, considering the competition of healthy vs. leukemic cell populations and three types of division that a stem-like cell can exhibit: self-renew, asymmetric division and differentiation. In the model it is assumed that the treatment acts on the proliferation rate of the leukemic stem cells and on the apoptosis of stem and mature cells. The emphasis in this model is on establishing relevant parameters for chronic and acute manifestations of leukemia. Stability of equilibria is investigated and sufficient conditions for local asymptotic stability will be given using a Lyapunov-Krasovskii functional.

  14. Purification and characterization of fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA)

    DEFF Research Database (Denmark)

    Hokland, P; Rosenthal, P; Griffin, J D;

    1983-01-01

    Fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA) were purified from both fetal liver and fetal bone marrow by immune rosetting with sheep erythrocytes coated with rabbit anti-mouse immunoglobulin and by fluorescence-activated cell sorting. Dual...... antigen. Furthermore, using methanol-fixed cells, it could be shown that approximately 20% contained intracytoplasmic mu chains (cyto-mu) and that approximately 15% were positive for the terminal transferase enzyme (TdT) marker. The CALLA+ fetal cells thus closely resemble the childhood acute...... lymphoblastic leukemia cell with respect to surface marker phenotype. A population of CALLA- cells devoid of mature erythroid and myeloid surface markers was found to contain higher numbers of TdT+ cells but lower numbers of cyto-mu, B1, and Ia+ cells than the CALLA+ subset. In vitro analysis of normal...

  15. A model with competition between the cell lines in leukemia under treatment

    International Nuclear Information System (INIS)

    The evolution of leukemia is modeled with a delay differential equation model of four cell populations: two populations (healthy and leukemic) ) of stem-like cells involving a larger category consisting of proliferating stem and progenitor cells with self-renew capacity and two populations (healthy and leukemic) of mature cells, considering the competition of healthy vs. leukemic cell populations and three types of division that a stem-like cell can exhibit: self-renew, asymmetric division and differentiation. In the model it is assumed that the treatment acts on the proliferation rate of the leukemic stem cells and on the apoptosis of stem and mature cells. The emphasis in this model is on establishing relevant parameters for chronic and acute manifestations of leukemia. Stability of equilibria is investigated and sufficient conditions for local asymptotic stability will be given using a Lyapunov-Krasovskii functional

  16. Carryover of bovine leukemia virus antibodies in samples from shared milk meters.

    Science.gov (United States)

    Nekouei, O A; Sanchez, J; Keefe, G P

    2015-08-01

    Screening for infectious diseases of cattle using milk from the dairy herd improvement (DHI) sampling process is very convenient. However, when samples from shared milk meters are used, carryover of antibodies or other diagnostic targets can complicate the interpretation of the diagnostic test results for diseases, including bovine leukosis. The objectives of this study were (1) to assess the potential for carryover of antibodies against bovine leukemia virus (BLV) in milk samples obtained from shared meters, and (2) to determine if adjustment of the diagnostic test cut-off value would improve the test characteristics for meter-collected milk ELISA results. Eight dairy farms were randomly selected from herds with a wide range of BLV prevalence levels in Prince Edward Island, Canada. Within each chosen farm, 2 to 4milk meters were randomly selected. During the routine procedures of DHI sampling, 2 simultaneous milk samples, 1 hand-collected at the beginning of milking (after udder preparation) and the other from the corresponding milk meter, were taken from all lactating cows (n=236) that were milked at the selected meters (n=26). The sequence of cows using each meter was recorded. All samples were tested for BLV antibodies using a commercial indirect ELISA. Antibody carryover potential was assessed in meter-collected samples which were preceded by other cows using the same meters. Applying the hand-collected sample results as our reference standard, a new cut-off was defined for meter-collected samples to optimize the test characteristics. At the standard cut-off value of the diagnostic test, 110 (46.6%) of the hand-collected and 136 (57.6%) of the meter-collected samples were positive. For low-titer cows (e.g., true negatives), the likelihood of antibody carryover significantly increased as the titer of preceding cows increased, whereas this change was not substantial for high-titer cows. The odds of obtaining false diagnoses in meter-positive samples became

  17. Herd-level risk factors for infection with bovine leukemia virus in Canadian dairy herds.

    Science.gov (United States)

    Nekouei, Omid; VanLeeuwen, John; Sanchez, Javier; Kelton, David; Tiwari, Ashwani; Keefe, Greg

    2015-05-01

    Enzootic bovine leukosis (EBL) is an economically important infection of dairy cattle worldwide, which is caused by bovine leukemia virus (BLV). The prevalence of infection in Canadian dairy herds is high and continues to increase; however, there has not been a national program to control BLV. This cross-sectional study was conducted to identify potentially important risk factors for BLV infection on Canadian dairy herds, which is a prerequisite to developing an effective control program. During 1998-2003, based on a stratified two-stage random sampling process, 315 dairy farms from seven provinces of Canada were selected. Within each farm, 9-45 cows were bled and tested with a commercial serum ELISA kit for BLV antibodies. A comprehensive questionnaire, targeting potentially important herd-level management indicators, was successfully administered in 272 herds. A zero-inflated negative binomial (ZINB) regression model was fit to the resulting data to assess the potential associations between BLV seropositivity and a variety of herd-level factors. Seventy-eight percent of the herds were identified as BLV-positive (had one or more test positive animals). In the negative-binomial part of the final ZINB model, herds with clinical cases of leukosis during the 12 months prior to sampling, as well as herds which purchased animals with unknown BLV infection status in the last five years, had a significantly larger proportion of BLV positive animals. Based on a significant interaction between two of the risk factors, changing gloves between cows during pregnancy examination was not statistically associated with lower proportion of infected cows compared with not changing gloves, in the western Canadian provinces. In the logistic part of the model, herds from eastern Canadian provinces and those not purchasing cows in the last five years had increased odds of being free from BLV. The high prevalence of infection across Canada should be addressed through the development and

  18. Renal complications in chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis: the Mayo Clinic experience.

    Science.gov (United States)

    Strati, Paolo; Nasr, Samih H; Leung, Nelson; Hanson, Curtis A; Chaffee, Kari G; Schwager, Susan M; Achenbach, Sara J; Call, Timothy G; Parikh, Sameer A; Ding, Wei; Kay, Neil E; Shanafelt, Tait D

    2015-09-01

    While the renal complications of plasma cell dyscrasia have been well-described, most information in patients with chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis is derived from case reports. This is a retrospective analysis of patients with chronic lymphocytic leukemia or monoclonal B-cell lymphocytosis who underwent kidney biopsy for renal insufficiency and/or nephrotic syndrome. Between January 1995 and June 2014, 49 of 4,024 (1.2%) patients with chronic lymphocytic leukemia (n=44) or monoclonal B-cell lymphocytosis (n=5) had a renal biopsy: 34 (69%) for renal insufficiency and 15 (31%) for nephrotic syndrome. The most common findings on biopsy were: membranoproliferative glomerulonephritis (n=10, 20%), chronic lymphocytic leukemia interstitial infiltration as primary etiology (n=6, 12%), thrombotic microangiopathy (n=6, 12%), and minimal change disease (n=5, 10%). All five membranoproliferative glomerulonephritis patients treated with rituximab, cyclophosphamide and prednisone-based regimens had recovery of renal function compared to 0/3 patients treated with rituximab with or without steroids. Chronic lymphocytic leukemia infiltration as the primary cause of renal abnormalities was typically observed in relapsed/refractory patients (4/6). Thrombotic microangiopathy primarily occurred as a treatment-related toxicity of pentostatin (4/6 cases), and resolved with drug discontinuation. All cases of minimal change disease resolved with immunosuppressive agents only. Renal biopsy plays an important role in the management of patients with chronic lymphocytic leukemia or monoclonal B-cell lymphocytosis who develop renal failure and/or nephrotic syndrome. PMID:26088927

  19. Serosurvey for feline leukemia virus and lentiviruses in captive small neotropic felids in São Paulo state, Brazil.

    Science.gov (United States)

    Filoni, Claudia; Adania, Cristina Harumi; Durigon, Edison Luiz; Catão-Dias, José Luiz

    2003-03-01

    Feline leukemia virus (FeLV), Gammaretrovirus, and feline immunodeficiency virus, a Lentivirus, are members of the family Retroviridae, and may establish persistent infections in the domestic cat (Felis catus). Cytoproliferative and cytosuppressive disorders may result from infection with these viruses. Morbidity and mortality rates are high in domestic cats worldwide. Infection of endangered neotropic small felids with these viruses could be devastating. To investigate the prevalence of FeLV and feline lentiviruses in neotropic small felids kept in captivity in São Paulo state. Brazil, serum samples from 104 animals belonging to the species Leopardus pardalis, Leopardus tigrinus, Leopardus wiedii, Herpailurus yaguarondi, and Oncifelis geoffroyi were tested for FeLV and feline lentiviruses by commercially available immunoassays. All results were negative, suggesting that retrovirus infection is not an important clinical problem in these populations. Because domestic cats in São Paulo city are naturally infected with these pathogens, and feral cats are commonly found in zoologic facilities in Brazil, preventive measures should be taken to avoid transmission of retroviruses to naive populations of wild and captive neotropic felids in Brazil. PMID:12723802

  20. Unusual immunophenotype of T-cell large granular lymphocytic leukemia: Report of two cases

    Directory of Open Access Journals (Sweden)

    Nikhil Rabade

    2015-01-01

    Full Text Available Large granular lymphocytes (LGL leukemias are commonly of the T-cell or NK-cell type. T-cell LGL leukemia is typically a disorder of mature CD3, CD8 and T-cell receptor TCR (TCR - T cell receptor-αβ positive cytotoxic T-cells. Rare variants include TCRγδ+ variants and CD4 + TCRαβ+ cases. We report a case of each of these rare variants. An 83-year-old female presented with anemia and lymphocytosis with LGLs on peripheral smear. Six-color multiparametric flowcytometric analysis showed expression of CD3, heterogeneous CD7, dim CD2 and TCRγδ and lacked expression of CD5, TCRαβ, CD56, CD4 and CD8. A final diagnosis of TCRγδ+ T-cell LGL leukemia was made. Differentiation between TCRγδ+ T-cell LGL leukemia and other γδ+ T-cell malignancies is of utmost importance due to the indolent nature of the former as compared to the highly aggressive behavior of the latter. An 85-year-old male diagnosed with liposarcoma was identified to have lymphocytosis during preoperative evaluation. Peripheral smear showed presence of LGLs. Flowcytometric immunophenotyping showed expression of TCRαβ, CD3, CD2, CD5, CD4, dim CD8, CD56 with aberrant loss of CD7 expression. Vβ repertoire analysis by flowcytometry showed 97% cells with Vβ14 clonality. A final diagnosis of TCRαβ+ CD4 + T-cell LGL leukemia was made. CD4 + T-cell large granular lymphocytic leukemias have an indolent, less aggressive course when compared to their CD8 + counterparts and are not necessarily associated with cytopenias. However, their association with secondary neoplasia (29% of the cases warrants a high degree of suspicion in the diagnosis as also noted in the index case. Use of a wide panel of antibodies and newer modalities such as Vβ repertoire analysis helps in accurate subtyping of LGL leukemia.