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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allogeneic fetal liver cell transplantation has been shown to be able to reconstitute lymphopoietic systems of mice when these systems are defective or destroyed. Lethally irradiated mice or mice with inherited severe combined immunodeficiency disease (SCID) were grafted with 14 days gestation allogeneic fetal liver cells, then subjected to a follow-up for the immune tolerance to the donor and the normal or subnormal immune reconstitution allowing prevention of diabetes in NOD mice or cure of leukemia in AKR mice and of immunodeficiency in SCID mice. Briefly, when normal CBA mice were lethally irradiated and then grafted with allogeneic fetal liver cells from Balb/c mice, a specific immune tolerance was induced to donor skin grafts. Unrelated skin grafts were rejected and a response to antigens was observed in these chimeras. However, despite the capacity to develop hyperacute rejection of skin allografts, following hyperimmunization, these chimeric mice did not produce anti-H2 cytotoxic antibodies. In SCID mice (CB17), the immune reconstitution occurred when mice were grafted with allogeneic (C57/B16) as well as with syngeneic fetal liver cells. Human cells were found in SCID mice following implantation of human fetal liver and thymus cells. When NOD mice were irradiated, then grafted with allogeneic fetal liver cells, a large part of donor cells were found in NOD recipients, correlating with a low incidence of diabetes. Leukemic AKR mice grafted with allogeneic fetal liver cells had virtually no leukemia relapse, suggesting a strong graft-versus-leukemia effect following such a transplant.
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PMID:Fetal liver cell transplantation in various murine models. 150 74

We studied the compatibility of human lymphocyte engraftment and susceptibility to HIV-1 infection in 2 new immunodeficient mice. NOD/Shi-scid mice were generated by backcrossing of the scid mutation into NOD mice while C57BL/6-RAG2(0/0) were generated by knocking out the RAG-2 gene. Human T lymphocytes were reconstituted in new immunodeficient mouse strains. We found that the new immunodeficient mouse strains accepted human PBL engraftment and HIV-1 infection more efficiently than conventional C.B-17-scid mice. Especially in the hu-PBL-NOD/Shi-scid strain, we reproduced the high levels of HIV-1 viremia comparable to or at significantly higher levels than after HIV-1 primary infection. These results indicate that our hu-PBL-NOD-scid animal is useful for investigations of the activation mechanism in HIV-1 replication in vivo and after primary infection.
Leukemia 1997 Apr
PMID:High levels of viremia in hu-PBL-NOD-scid mice with HIV-1 infection. 920 14

On the subject of acute myeloid leukemia (AML), there is little consensus about the target cell within the hematopoietic stem cell hierarchy that is susceptible to leukemic transformation, or about the mechanism that underlies the phenotypic, genotypic and clinical heterogeneity. Here we demonstrate that the cell capable of initiating human AML in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice) - termed the SCID leukemia-initiating cell, or SL-IC - possesses the differentiative and proliferative capacities and the potential for self-renewal expected of a leukemic stem cell. The SL-ICs from all subtypes of AML analyzed, regardless of the heterogeneity in maturation characteristics of the leukemic blasts, were exclusively CD34++ CD38-, similar to the cell-surface phenotype of normal SCID-repopulating cells, suggesting that normal primitive cells, rather than committed progenitor cells, are the target for leukemic transformation. The SL-ICs were able to differentiate in vivo into leukemic blasts, indicating that the leukemic clone is organized as a hierarchy.
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PMID:Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. 921 98

To understand the role of key molecules in determining the strength and nature of allogeneic T-cell response to leukemia, we transfected HLA-DR1 into the major histocompatibility complex (MHC)-deficient, natural killer (NK)-cell sensitive K562 leukemia cell line. Untransfected K562 cells stimulated NK proliferation in vitro and formed subcutaneous tumors in severe combined immunodeficiency/non-obese diabetic (SCID/NOD) mice. Tumor growth was inhibited by adoptive intravenous transfer of fresh unprimed peripheral blood mononuclear cells (PBMC). In contrast, HLA-DR1 transfected cells stimulated CD4(+) T cells, but not NK-cell proliferation in vitro and formed tumors resistant to fresh PBMC in SCID/NOD mice. Tumors not expressing MHC were infiltrated with CD16(+)CD56(+) lymphocytes whereas nonregressing HLA-DR1 expressing tumors showed only a scanty infiltration with both T-cell and NK-cell subsets. The results indicate that MHC class II expression by leukemia cells can determine the effector cell type that it engages. In vivo MHC class II expression rendered K562 cell tumors resistant to NK-cell mediated antitumor reactivity.
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PMID:Regulation of a graft-versus-leukemia effect by major histocompatibility complex class II molecules on leukemia cells: HLA-DR1 expression renders K562 cell tumors resistant to adoptively transferred lymphocytes in severe combined immunodeficiency mice/nonobese diabetic mice. 937 66

Granulocyte-macrophage colony-stimulating factor (GM-CSF ) and tumor necrosis factor alpha (TNFalpha) have been implicated in the pathogenesis of the fatal childhood disease termed juvenile myelomonocytic leukemia (JMML). We used a severe combined immunodeficient/nonobese diabetic (SCID/NOD) mouse model of JMML and examined the effect of inhibiting these cytokines in vivo with the human GM-CSF antagonist and apoptotic agent E21R and the anti-TNFalpha monoclonal antibody (MoAb) cA2 on JMML cell growth and dissemination in vivo. We show here that JMML cells repopulated to high levels in the absence of exogeneous growth factors. Administration of E21R at the time of transplantation or 4 weeks after profoundly reduced JMML cell load in the mouse bone marrow. In contrast, MoAb cA2 had no effect on its own, but synergized with E21R in virtually eliminating JMML cells from the mouse bone marrow. In the spleen and peripheral blood, E21R eliminated JMML cells, while MoAb cA2 had no effect. Importantly, studies of mice engrafted simultaneously with cells from both normal donors and from JMML patients showed that E21R preferentially eliminated leukemic cells. This is the first time a specific GM-CSF inhibitor has been used in vivo, and the results suggest that GM-CSF plays a major role in the pathogenesis of JMML. E21R might offer a novel and specific approach for the treatment of this aggressive leukemia in man.
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PMID:Inhibition of granulocyte-macrophage colony-stimulating factor prevents dissemination and induces remission of juvenile myelomonocytic leukemia in engrafted immunodeficient mice. 938 8

Long-term cultures (LTC) and immunodeficient (NOD/SCID) mice have been used to quantitate and characterize primitive malignant progenitors from patients with acute myelogenous leukemia (AML). In 5-week-old LTC of cells from newly diagnosed patients with AML cytogenetically abnormal as well as normal progenitors could be easily detected and their numbers increased by cytokine supplements to the cultures. Sixty percent of AML samples will engraft in NOD/SCID mouse marrow. The frequency and level of engraftment of human cells detected appears to vary among the different subtypes of AML but is not generally affected by treatment of the mice with human cytokines. Both the LTC and NOD/SCID mouse assay show promise as tools to allow characterization of differences between leukemic stem cells which maintain malignant hematopoiesis in individual patients and, more importantly, between these cells and their normal stem cell counterparts.
Leukemia 1997 Dec
PMID:Cytokine responsiveness of primitive progenitors in acute myelogenous leukemia. 944 47

The non-obese diabetic-severe combined immunodeficiency (NOD-SCID) mouse is a convenient host for human hematopoietic tissues and cells. Human fetal bone fragments engrafted subcutaneously in NOD-SCID mice sustain human hematopoiesis for several months. MS5 murine bone marrow stromal cells were transfected by electroporation with a plasmid containing the human interleukin-3 gene. As expected, stably transfected hu-IL3-MS5 cells supported human hematopoiesis in vitro more efficiently than MS5 cells. hu-IL3-MS5 cells were then injected intravenously into hu-NOD-SCID mice to test their ability to home to the mouse and/or human bone marrow, and to evaluate the role of hu-IL3 secretion on human hematopoiesis in vivo. hu-IL3 was detected in the mouse serum for up to an observation time of 8 weeks. hu-IL3-MS5 cells engrafted the bone marrow, spleen, liver and lungs of the mice but also the human bone graft. The presence of hu-IL3-MS5 cells in the human bone significantly stimulated local human hematopoiesis. This setting could be used to model the bone marrow homing of intravenously injected stromal cells or stromal cell precursors. The same experimental principle could also be applied in a therapeutic perspective to malignant human bone marrow hematopoiesis.
Leukemia 1998 Jul
PMID:Transplantation of stromal cells transduced with the human IL3 gene to stimulate hematopoiesis in human fetal bone grafts in non-obese, diabetic-severe combined immunodeficiency mice. 966

Factors that may improve retroviral transduction of primitive human hematopoietic cells were studied using MFG-based vectors containing a LacZ gene and produced either by a murine (psi-Crip) or a human (Tasaf) cell line. Cord blood (CB) or bone marrow (BM) CD34+ cells were stimulated and transduced in the presence of three cytokines (interleukin 3 [IL-3], IL-6, and stem cell factor [SCF; c-Kit Ligand]). In the supernatant infection protocol, hematopoietic progenitor cells as measured by X-Gal staining of colony-forming unit cells (CFU-Cs) were transduced more effectively with Tasaf (20%) than with psi-Crip (8%). In contrast, there was no difference between these two cell lines in a coculture protocol. However, gene transfer into more primitive CD34+CD38- subsets and in LTC-IC-derived colonies was low. The use of a large number of cytokines including FLT3-L and PEG-rhMGDF increased the transduction efficiency into CD34+CD38(-)-derived CFU-Cs (35% by PCR) or LTC-ICs (10%). A virus pseudotyped with gibbon ape leukemia virus (GALV) envelope further improved gene transfer to 60 and 48% for LacZ+ CFU-C- and LTC-IC-derived colonies, respectively. These conditions of transduction allowed multilineage engraftment of primitive cord blood cells in NOD-SCID mice. Moreover, 10% (at least) of the human hematopoietic cells recovered from the marrow of these immunodeficient animals were transduced. These data suggest that the efficiency of transduction of human hematopoietic primitive cells can be significantly improved by judicious combinations of recombinant cytokines and high retroviral titers.
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PMID:Retrovirus-mediated gene transfer into human CD34+38low primitive cells capable of reconstituting long-term cultures in vitro and nonobese diabetic-severe combined immunodeficiency mice in vivo. 968 21

Non-obese diabetic NOD/SCID mice have been used to grow human leukaemia as a systemic disease. The animals were inoculated with leukaemic cells obtained from a 36-year-old male with early B-cell precursor acute lymphoblastic leukaemia and on day 15 were given the first of three weekly injections of 1 mg/kg vincristine or equimolar liposomal vincristine. The development of leukaemia in the mice was monitored by taking weekly blood samples and measuring the cell content by flow cytometry. The median time to 50% human cells in the peripheral blood of mice treated with free vincristine was 41 d from the start of treatment compared with 49 d for mice treated with liposomal vincristine (P < 0.01). The median day of death for mice treated with free vincristine was 47 d from the start of treatment and 57 d for mice receiving liposomal vincristine (P<0.01), thus providing a 21% increase in lifespan for animals treated with the liposomal preparation. There was slightly greater weight loss in mice treated with free vincristine than those given liposomal vincristine. Measurement of in vitro colony forming bone marrow progenitor cells in similarly treated, tumour-free mice, showed no difference in progenitor cell survival between mice that received either type of vincristine. We conclude that encapsulating vincristine in liposomes improves the therapeutic index of this drug measured in mice bearing human leukaemia. This may lead to use of the drug in conventional combination chemotherapy with greater safety or, in this setting, at higher dosage.
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PMID:Liposomal vincristine for the treatment of human acute lymphoblastic leukaemia in severe combined immunodeficient (SCID) mice. 972 98

We report here on a novel stromal cell line, AGM-S3, derived from the aorta-gonad-mesonephros (AGM) region of a 10.5 days postcoitum (dpc) mouse embryo. The AGM-S3 cells promoted production of hematopoietic progenitors and day-12 spleen colony-forming cells from Lin-c-Kit+Sca-1(+) murine primitive hematopoietic cells. They also supported for 6 weeks generation of human multipotential progenitors from cord blood CD34(+)CD38(-) primitive hematopoietic cells. Human long-term repopulating hematopoietic stem cells (LTR-HSC) with the potential to reconstitute hematopoiesis in NOD/SCID mice were maintained on AGM-S3 cells for at least 4 weeks. Flow cytometric analysis showed that CD13, vascular cellular adhesion molecule-1, and Sca-1 were expressed on AGM-S3 cells. Because stem cell factor, interleukin-6 (IL-6), and oncostatin M, but not IL-3, IL-11, leukemia- inhibitory factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, thrombopoietin, and Flk2 ligand were detected in reverse transcription-polymerase chain reaction analysis of AGM-S3 cells, the cells seem to express species-cross reactive molecule(s) other than the cytokines examined and which act on primitive hematopoietic progenitor/stem cells. This cell line is expected to elucidate molecular mechanisms regulating early hematopoiesis and pave the way for developing strategies for expansion of human transplantable HSC.
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PMID:Stimulation of mouse and human primitive hematopoiesis by murine embryonic aorta-gonad-mesonephros-derived stromal cell lines. 973 Oct 61


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