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

A phase I/II study of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 24 leukemia patients was conducted at our institute. Recombinant human G-CSF (50-200 micrograms/m2/day) was administered i.v. In seven allogeneic bone marrow transplantation (BMT) recipients, treatment with rhG-CSF was started 5 days after BMT. Neutrophils began to increase within 3 days after the start of rhG-CSF administration in five of seven patients. The mean duration necessary for recovery of neutrophils to greater than 500/microliters was 11.3 days after BMT with rhG-CSF; 26.8 days is the figure for recovery without rhG-CSF from Japanese historical data. In seven out of eight patients who received rhG-CSF administration after the first remission-induction chemotherapy, the neutrophil counts increased from less than 300/microliters to greater than 4000/microliters within 10 days. Blasts did not increase in all patients including four acute nonlymphocytic leukemia (ANLL) patients. Severe infections such as septicemia and pneumonia, which were unable to be controlled by antibiotics only, were successfully treated with rhG-CSF and antibiotics. rhG-CSF either stimulated or inhibited myeloid leukemic cells in some refractory cases. Mild bone pain occurred in one patient while receiving rhG-CSF i.v. rhG-CSF seems to have the ability to shorten the period of neutropenia, prevent infections after allogeneic BMT and remission-induction chemotherapy for acute leukemia, and support therapy for infections.
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PMID:Clinical effects of recombinant human granulocyte colony-stimulating factor in leukemia patients: a phase I/II study. 247 58

We tested purified recombinant hemopoietic factors for their effects on the proliferation and differentiation of murine myelomonocytic leukemia cells (WEHI-3B-Y1) in serum-free agar culture. We found that purified recombinant human G colony-stimulating factor (CSF) markedly increased the colony number of WEHI-3B-Y1 cells and differentiation-inducing activity. However, at low colony densities [( 100/dish), G-CSF did not induce the differentiation of WEHI-3B-Y1 cells. We conclude that G-CSF does not induce the differentiation of WEHI-3B-Y1 cells directly, but induce the differentiation as a result of the secondary autoinduction of differentiation. Interleukin 3 (IL-3) slightly enhanced but erythropoietin (Epo) did not alter the colony number of WEHI-3B-Y1 cells. GM-CSF or M-CSF decreased the colony number of WEHI-3B-Y1 cells. Such purified recombinant human IL-3, Epo, GM-CSF and M-CSF did not induce morphologically the distinct differentiation of WEHI-3B-Y1 cells.
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PMID:[Clonal response of murine myelomonocytic leukemia cells (WEHI-3B-Y1) to purified recombinant human hemopoietic factors in serum-free culture]. 248 48

We have tested a panel of recombinant hematopoietic growth factors (HGF) including the interleukins (IL) 1, 2, 3, 4, and 6 and the colony stimulating factors GM-CSF, G-CSF, M-CSF for their ability to induce proliferation of precursor B acute lymphoblastic leukemia cells (ALL) from 19 patients. In Ficoll-Isopaque isolated and T cell-depleted ALL bone marrow samples, IL2 (two cases), IL3 (four cases), and GM-CSF (one case) infrequently stimulated DNA synthesis measured by 3H-thymidine (TdR) uptake, and the other recombinant growth factors completely failed to do so. In repeat experiments with ALL blasts purified by fluorescence activated cell sorting (FACS), IL2, IL3, and GM-CSF responses could not be reproduced, suggesting that nonleukemic contaminant cells, and not the ALL blasts, had been stimulated by these factors. Cocktails containing combinations of IL1-IL4 and IL6 also lacked proliferation inducing potency. Depending on the purity of the incubated ALL cell samples, an impure preparation of B cell growth factors that has been reported to contain a highly effective stimulatory activity for precursor B ALL cells induced proliferation of residual normal cells as well as the ALL cells, as was evident from combined analysis of DNA synthesis and karyotyping. Exposure of the ALL blasts to artificial activators of protein kinase C and Ca2+ mobilization resulted in significant rises in 3H-TdR uptake, suggesting that these intracellular compounds are involved in transducing signals that upregulate proliferation. Although it remains possible that some of the human recombinant growth factors promote the growth of precursor B ALL cells in combination with other stimuli, a dominant role in the regulation of proliferation of these cells cannot be attributed to any of these cytokines at the present time.
Leukemia 1989 May
PMID:Recombinant hematopoietic growth factors fail to induce a proliferative response in precursor B acute lymphoblastic leukemia. 249 81

PGM-1 is a transplantable leukemia of C3H/HeJ mice growing as a population of undifferentiated blast cells with a predisposition to form subcutaneous tumors and to grow in lymphoid organs. Cell survival and proliferation in vitro are absolutely dependent on stimulation by hemopoietic growth factors, and up to 100% of tumor cells can form colonies of mature granulocytes and/or macrophages in semisolid cultures, the colonies containing no clonogenic cells. Most clonogenic cells in the leukemic population respond to stimulation by multi-colony-stimulating factor (IL-3) or GM-CSF, but some respond also to M-CSF, G-CSF, IL-4, IL-5, or IL-6. In their surface phenotype and proliferative characteristics in vitro, PGM-1 leukemic cells resemble normal granulocyte-macrophage progenitor cells, and the leukemia may be a useful model for human chronic myeloid leukemia.
Leukemia 1989 Nov
PMID:PGM-1: a transplantable murine leukemia of granulocyte-macrophage progenitor cells. 268 46

The chromosome alterations specifically associated with leukaemia are found largely in the regions where the genes for the haemopoietic growth factors (as well as other regulatory molecules or their receptors) are located, indicating a crucial role of the growth factors in leukaemogenesis. However, growth factor genes per se do not generally induce leukaemia when inserted into normal haemopoietic cells, although they will do so if they are inserted into immortalized haemopoietic stem cell lines. The response of AML cells to these growth factors is extremely heterogeneous, and the tilting of the balance between self-reproduction (leading to perpetuation of the leukaemic process) and differentiation ('death' of the malignant cells) depends on several parameters, on the type and combination of factors to which the cells are exposed, with IL-3 and GM-CSF tending to favour self-renewal, and G-CSF and M-CSF tending to favour differentiation. These findings open the possibility to consider the use of growth factors to control the leukaemic process, although such treatment should be approached with considerable caution, and on an individual patient basis.
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PMID:Haemopoietic growth factors: their role in acute myeloblastic leukaemia. 268 18

The proliferative and maturation abilities of bone marrow progenitors in patients with refractory anemia with excess of blasts (RAEB) and RAEB in transformation (RAEB-T) have previously been investigated in vitro using impure sources of colony stimulating activity. Here we report studies that were concerned with defining growth factor responses of RAEB progenitors (RAEB-CFU) in colony culture using pure hematopoietic growth factors. Marrow cells of 10 RAEB patients were cultured with recombinant IL3, GM-CSF, G-CSF, M-CSF and EPO. Factor dependent colony growth of four patients was examined in detail cytologically. The analysis revealed notable deficiencies in the colony forming spectrum as compared with normal marrow: although granulocytic colonies were formed in all of these four RAEB cases, macrophage colonies could not be induced in 1/4 cases and eosinophilic and erythroid colony formation could not be propagated in 2/4 cases with the proper stimuli. These findings are indicative of the intrinsic incapabilities of RAEB-CFU to mature along certain differentiation pathways in response to the growth factors. We then determined the surface phenotypes of RAEB-CFU using MoAbs Vim-2 (myelomonocytic) and B13C5 (CD34) following dual labeling and fluorescence activated cell sorting and subsequent culture of the separately sorted BI3C5+/Vim-2+, BIC5+/Vim-2-, BI3C5-/Vim-2+ and BIC5-/Vim-2- cells. In normal marrow most clonogenic cells were recovered from the BI3C5+/Vim-2- fraction. In contrast, in RAEB marrow increased proportions of the colony forming cells were BI3C5+/Vim-2+, BI3C5-/Vim-2+, or BI3C5-. The altered distribution of surface immunophenotypes of RAEB-CFU provides further evidence for the imbalance of maturation in the progenitor cell compartment. The results are discussed in view of the concept that the inabilities of the RAEB hematopoietic precursors to mature in response to the hematopoietic growth factors are partial and variable, but may culminate in a progressive loss of the differentiation competence of the progenitors when leukemia evolves.
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PMID:Characterization of clonogenic cells in refractory anemia with excess of blasts (RAEB-CFU): response to recombinant hematopoietic growth factors and maturation phenotypes. 278 35

We have examined the efficacy of various drugs in 44 patients with MDS and found the different effectiveness which depends on the type of MDS. Namely, RA appears to respond to steroid hormone, androgen, and/or vitamin D3, regardless of single or combined use. In particular, it is obvious in androgen, and as our previous reports, high content of acidic ferritin in RBC with RA have changed to more basic ones by treatment with androgen. On the contrary, these drugs were not effective on RAEB, RAEB-T, and CMML. A long-term observation is needed to determine whether the prolonged or decreased occurrence of leukemia could be obtained in the effective cases with RA. Most of the cases who did not develop overt leukemia during this study died of bleeding or infections due to thrombocytopenia or leukocytopenia, thus indicating that supportive therapies are important in patients with MDS. Since it has recently been reported that recombinant G-CSF or GM-CSF is helpful to increase the number of leucocyte and to enhance their functional recovery in MDS, these factors may be powerful agents against infections when they are carefully used with regard to the activation of leukemic clones.
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PMID:[Therapy of the preleukemic state: effect of androgens on refractory anemia]. 283 1

Activation of T cells by an antigen, a mitogen, or a combination of a phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA]) and a calcium ionophore (A23187) leads to induction of a set of lymphokine genes. Treatment of human T-cell leukemia line Jurkat by a mitogen or p40x, a transactivator protein encoded by human T-cell leukemia virus type I, activates many transfected lymphokine genes in a transient transfection assay. To study the mechanism of lymphokine gene induction, we examined the effects of mitogen stimulation and p40x on the gene for the mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) in Jurkat cells. Deletion and mutation analyses showed that the 5'-flanking region of the gene for the GM-CSF is composed of two types of regulatory elements. One sequence, located at positions -95 to -73, determines response to stimulation by either TPA-A23187 or p40x. This region contains conserved lymphokine element 2, which appears in the gene for interleukin 3 (IL-3) and is followed by a GC-rich stretch. This GC-rich stretch alone specifies inducible response to p40x but not to TPA-A23187. Another sequence, located at positions -113 to -96 upstream of a TATA-like sequence, mediates inducible response to p40x but not to TPA-A23187. This sequence includes conserved lymphokine element 1, which appears in several lymphokine-cytokine genes, such as those for IL-3, G-CSF, and IL-2. We previously showed that the simian virus 40 early region promoter was also induced by a mitogen or p40x in Jurkat cells. Deletion analysis showed that the minimum region require for stimulation by both signals are identical. These results, which indicate that p40(x) stimulates transcription of the gene for the GM-CSF or the simian virus 40 early region promoter through the same DNA element or an overlapping DNA element required for induction by a mitogen, lend further support to the notion that p40(x) can exert its function by activating a component(s) of the T-cell signal transduction pathway which is activated by an antigen or a mitogen.
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PMID:T-cell activation signals and human T-cell leukemia virus type I-encoded p40x protein activate the mouse granulocyte-macrophage colony-stimulating factor gene through a common DNA element. 285 2

The development of semisolid culture methods supporting the clonal proliferation and maturation of granulocytes and macrophages led to the discovery of a group of specific glycoproteins, the colony-stimulating factors (CSFs), whose function it is to control the proliferation and functional activity of granulocytes, macrophages and associated blood cells. The four known CSFs in the mouse and man have been purified and complementary DNAs (cDNAs) for each have been cloned. The injection of bacterially synthesized recombinant CSF into mice has demonstrated that these CSFs can function in vivo to regulate granulocyte and macrophage formation. A major physiological role played by these CSFs is to control resistance to invading microorganisms through mechanisms capable of extremely rapid activation. Because the CSFs are the only known proliferative factors for these cells, the CSFs are involved in the initiation and the emergence of myeloid leukaemia but, conversely, at least one of the CSFs, G-CSF, is able to suppress myeloid leukaemic populations because of the ability of the CSFs to initiate differentiation commitment in responding granulocytic and macrophage populations. The CSFs are promising agents for clinical use in the treatment of infections in patients with depressed granulocyte-macrophage formation and possibly in the management of some types of myeloid leukaemia.
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PMID:The Wellcome Foundation lecture, 1986. The molecular control of normal and leukaemic granulocytes and macrophages. 288 49

The differentiation of leukemic cells in vivo can be a useful approach to therapy. In vivo differentiation of myeloid leukemic cells was studied in intraperitoneally implanted diffusion chambers, containing different soluble antigens. The presence of these antigens in the chambers induced differentiation of myeloid leukemic cells and this was inhibited in immune-deficient mice. Transfer of normal spleen cells enriched for T-lymphocytes or antigen-specific helper T lymphocyte cell lines to mice in which differentiation of leukemic cells was inhibited, restored in vivo differentiation of the leukemic cells. Antigen-specific helper T cells produce myeloid regulatory proteins and can accumulate at a site that contains the specific antigen. It is suggested that migration in response to antigen of helper T cells producing regulatory proteins may play an important role in inducing in vivo differentiation of leukemic cells. We have identified a class of myeloid leukemic cells that can be induced to differentiate in vitro by incubation with pure MGI-1GM (GM-CSF) or IL-3, but not with MGI-1G (G-CSF). Experiments with pure recombinant proteins have shown that MGI-1GM and IL-3, but not MGI-1G, can also induce these myeloid leukemic cells to differentiate in vivo. These results and our previous studies on the myeloid cell differentiation-inducing protein MGI-2, demonstrate the potential use of normal hematopoietic regulatory proteins not only in regulation of normal hematopoiesis, but also in the treatment of myeloid leukemia by in vivo induction of terminal cell differentiation.
Leukemia 1988 Dec
PMID:Control of in vivo differentiation of myeloid leukemic cells. 297 6


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