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

Colony-stimulating factor-1 (CSF-1 or M-CSF) supports the proliferation and survival of mononuclear phagocytes by binding to a receptor (CSF-1R) encoded by the c-fms proto-oncogene. Whereas the CSF-1R kinase is normally regulated by ligand, receptors bearing 'activating mutations' act constitutively as enzymes and can transform fibroblasts and haemopoietic cells of different lineages. Introduction of human CSF-1R enables mouse NIH-3T3 cells to form colonies in agar in response to human CSF-1 and to proliferate in serum-free medium supplemented with CSF-1, albumin, transferrin and insulin. Similarly, expression of human CSF-1R in interleukin 3-dependent mouse FDC-P1 myeloid cells enables them to grow in CSF-1. High levels of CSF-1R expression in FDC-P1 cells can induce factor-independent growth which is abrogated by a 'neutralizing' monoclonal antibody to the receptor. Therefore, critical mutations in the c-fms gene or overexpression of CSF-1R in immature myeloid precursors might each contribute to leukaemia.
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PMID:Signal-response coupling mediated by the transduced colony-stimulating factor-1 receptor and its oncogenic fms variants in naive cells. 215 60

Previous studies have indicated that colony-stimulating factors may stimulate myelopoiesis and thus increase the number of circulating white blood cells in patients with hematopoietic failure including aplastic anemia. However, long-term administration of the factor was required to maintain its response. In the present article we report on a patient with severe aplastic anemia undergoing treatment with recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF). After an initial response, the patient became refractory to GM-CSF. However, treatment with interleukin (IL)-3 restored responsiveness to GM-CSF, suggesting that IL-3 may have replenished the bone marrow with myelopoietic progenitor cells sensitive to the action of GM-CSF. This observation suggests the value of application of sequentially acting hematopoietic growth factors in aplastic anemia patients.
Leukemia 1990 Oct
PMID:In vivo recruitment of GM-CSF-response myelopoietic progenitor cells by interleukin-3 in aplastic anemia. 221 70

We showed that these two cell lines obviously expressed megakaryocytic phenotypes, such as multilobular, hyperploid nuclei, expression of GPIIb/IIIa complex, GPIb and PPO, although they have been originated from patients with leukemia. Furthermore, these cells had following characteristics. First, they responded to various kinds of hemopoietic factors. Especially, UT-7 cells were solely dependent on GM-CSF, IL-3 or Ep. Therefore UT-7 cells are useful to the assay of these factors as megakaryocytic cells. These facts provide us with new questions: why they are dependent on plural number of factors? How are the expressions of their receptors controlled. Is there an "autocrine" mechanism controlling their growth? Among these questions, we have just started with the Ep receptors, and most of the problems remain to be clarified. Second, PMA treatment suppressed their growth, but enhanced their differentiation and maturation. Among the megakaryocytic phenotypes, increase in GPIIb/IIIa complex, determined by a biochemical method, PPO by ultrastructural study, and the increase in cellular ploidy were clearly observed by PMA treatment. The phorbol ester PMA is well known to induce the differentiation of various kinds of leukemic cells (Rovera et al., 1979). Detailed molecular basis to clarify why the same PMA treatment causes differentiation into different cell lineages, dependent on cellular origin of the target cells, should be further studies. Third, the cells produced hemopoietic growth factors by PMA treatment, the majority of which was GM-CSF. Humoral control of megakaryopoiesis still remains unsettled. Our study may shed a light on its "multistep" regulatory mechanisms. Availability of a large amount of homogeneous megakaryocytic populations, which are responsive to hemopoietic factors and phorbol ester, will provide us with a great deal of informations concerning the molecular insight of megakaryocytopoiesis and thrombocytopoiesis.
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PMID:Growth and differentiation of two human megakaryoblastic cell lines; CMK and UT-7. 221 43

Conditioned medium from mitogen stimulated normal peripheral blood lymphocytes (PBL) has been demonstrated to contain a maturation inducer activity mediating the differentiation of human myeloid leukemia cells to monocytes and macrophages. The maturation inducer activity was isolated by salt precipitation, Sepharose CL-6B ion exchange and affinity chromatographies and electrophoresis. Two separate activities with M.W. ranges of 52-56 and 32-35 kDa capable of mediating the terminal differentiation of leukemic HL-60 promyelocytes to monocytes and macrophages were detected. The higher molecular weight species was determined to be a 54 kDa single polypeptide and was found to be distinct from IL-3 and IL-6 by ELISA and differentiation blocking assay. The inducing activity of the 32-35 kDa material was largely neutralized after treatment with anti-IL-3, but not with other antibodies. Employing the immunofluorescent antibody technique, the 54 kDa protein was detected on the surface membranes of PBL. The proportions and number of maturation inducer bearing lymphocytes in patients with acute myelogenous leukemia (0.4% and 35/mm3, respectively) were significantly lower than that of healthy donors (7.9% and 178/mm3) The role of these physiological factors in leukemia cell differentiation is discussed.
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PMID:Two separate differentiation inducing proteins for human myeloid leukemia cells and their isolation from normal lymphocytes. 223 10

In patients with acute myeloblastic leukemia incomplete response to induction chemotherapy and short disease-free survival may be related to cell kinetic quiescence of leukemic cells. In this in vitro study, we tested the hypothesis that treatment with cytokines and subsequent chemotherapy (ARA-C, daunorubicin) can increase proliferation and enhance leukemic cell kill. We evaluated the effects of recombinant human interleukin-3 (rh-IL-3), granulocyte-macrophage colony stimulating factor (rhGM-CSF) and granulocyte colony stimulating factor (rhG-CSF) alone and in combination on AML (N = 11) and blastic phase CML (N = 3) samples. Cellular DNA and RNA, incorporation of bromodeoxyuridine (BrdU), cell growth fraction, cell viability, and differentiation markers were evaluated in vitro. A decrease of the quiescent cell population (p = 0.003) and an increase in S-phase cells (p = 0.001) was observed in 8/11 AML samples treated with cytokine combinations. Pronounced heterogeneity or proliferative response was seen between individual cases and different cytokines, but in the majority of the samples IL-3 was most effective. Significantly increased Ki67 expression (p = 0.009) and BrdU incorporation (p = 0.01) were also found after exposure to cytokines indicating an increase in growth fraction. DNA synthesis time was unaffected. Eight samples of AML were treated for 24 hr with ara-C following 2 days of in vitro cytokine incubation. Evaluation of leukemic cell kill showed increased cytotoxicity in three of those five samples which had significant depletions of G0 cells and increases in S-phase. None of the leukemic samples without recruitment from G0 had an increase in ARA-C cytotoxicity. This study provides detailed cell kinetic analysis of cytokine effects on AML blasts and provides a rationale for a novel approach to the treatment of AML.
Leukemia 1990 Dec
PMID:Kinetic rationale for cytokine-induced recruitment of myeloblastic leukemia followed by cycle-specific chemotherapy in vitro. 224 6

Using (a) somatic cell hybrids retaining partial chromosome 5 and (b) clinical samples from patients with acquired deletions of the long arm of chromosome 5, combined with chromosome 5-linked DNA probes, some of which exhibited RFLPs, we have determined the order of a series of genes on chromosome 5. The order established is 5pter----MLVI-2----cen----HEXB----DHFR----Pi227- --- cp12.6----(IL5,IL4)----IL3----GMCSF---- FGFA---- (CSF1R,PDGFR)----(treC,ADRBR)----(ARH-H9,CSF1 )----qter. The suggested order and orientation for the closely linked IL3/GMCSF gene pair is cen----5' IL3 3'----5' GMCSF 3'----qter, on the basis of analysis of the GMCSF rearrangement in HL60 DNA. The map position of the GRL locus, which was consistent with both somatic cell hybrid and 5q- analyses, was telomeric to GMCSF and centromeric to CSF1R/PDGFR, near FGFA. Long-range restriction-enzyme analysis of 5q- DNAs did not detect rearrangements of 5q-linked probes except in HL60 DNA, but it did reveal putative long-range RFLPs of several loci. RFLPs for GRL, Pi227, cp12.6, IL3, and CSF1R can detect deletions in bone marrow and in leukemia cells from patients with acquired 5q deletions.
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PMID:Order of genes on human chromosome 5q with respect to 5q interstitial deletions. 229 53

Examples are presented in which normal as well as abnormal chromosome distributions could be obtained from the same individual by means of bivariate flow karyotyping. Selective stimulation of T-lymphocytes obtained by E-rosetting from the blood of a patient with acute myelocytic leukemia resulted in a normal flow karyogram. The specific stimulation of myelocytic leukemia cells with granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 3 (IL-3) yielded flow karyograms displaying the leukemia-associated chromosome abnormalities. The resulting flow karyograms could be used to discriminate between homolog differences, which appear normally in virtually every individual, and leukemia-associated chromosomal aberrations. In the case of a female chronic myelocytic leukemia patient who received bone marrow form an HLA-identical male donor, specific stimulation of various subsets of cells enabled to discriminate between leukemic host cells and non-leukemic donor cells. Both the leukemia-specific translocations and sex chromosomes were used as markers to analyse the flow karyograms obtained from the same sample.
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PMID:Clinical applications of flow karyotyping in myelocytic leukemia by stimulation of different subpopulations of cells in blood or bone marrow samples. 230 58

We investigated the effects of interleukin-7 (IL-7), a stromal cell derived cytokine known to stimulate proliferation of murine lymphoid precursor cells, alone and in combination with IL-3, IL-1, and IL-6 on proliferation of purified blast cells in acute lymphoblastic leukemia (ALL). After 7 days of liquid culture DNA-synthesis was induced in six of 10 cALL, three of five B-ALL, and two of seven T-ALL samples by IL-7 or IL-3 or both. Monitoring of leukemic cell populations in suspension culture by Southern blot analysis of immunoglobulin and T cell receptor gene rearrangements revealed preferential stimulation of the leukemic cell clone by both IL-7 or IL-3 in one cALL and one B-ALL sample. In these cases the combination of IL-7, IL-3, and IL-1 was as effective in stimulation of DNA-synthesis as the most potent cytokine alone. There was no evidence of lymphoid maturation during liquid culture as defined by immunophenotyping using flow cytometry. Stimulation of nonleukemic cell population seen in two other cases of cALL was associated with residual erythroid and granulocyte-macrophage colony forming cells after liquid culture as defined in parallel clonogenic assays in one and detection of CD 33+ and CD 13+ cells after culture in the other cALL sample. We conclude that IL-7 directly stimulates monoclonal growth of leukemic cells in a subset of ALL without evidence of concurrent maturation induction.
Leukemia 1990 Aug
PMID:Effects of recombinant human IL-7 on blast cell proliferation in acute lymphoblastic leukemia. 238 82

Populations of interleukin 3 (IL 3)-dependent cells can be derived from mouse bone marrow that display natural cytotoxicity (NC) against Wehi-164 target cells but do not display natural killing against YAC-1 cells. These bone marrow-derived NC cells cultured up to 2 mo in IL 3 do not contain rearranged T cell receptor beta-chain genes. They appear to be mast-like cells by electron microscopy and contain heterogeneous type granules. The molecules that mediate NC appear to be contained in these granules and are preformed because protein synthesis inhibitors have no effect on the capacity of IL 3-dependent NC cells to lyse Wehi-164 target cells. In addition to the IL 3-dependent bone marrow-derived cells, the basophilic leukemia cells, RBL-1, but not P815 mastocytoma cells were found to mediate NC against Wehi-164 cells. Both bone marrow-derived NC and RBL-1 cells can lyse L929 cells in 18 hr, suggesting that the putative NC mediator may be related to lymphotoxin/tumor necrosis factor (TNF). Recombinant human TNF displayed identical properties as NC cells; both entities possessed the same target cell specificity and had similar kinetics of target cell killing. The use of polyclonal rabbit antimouse TNF antibody blocked the actions of NC cells. Thus we believe that the mediation of NC is through the actions of a TNF-like molecule.
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PMID:Morphology and lytic mechanisms of interleukin 3-dependent natural cytotoxic cells: tumor necrosis factor as a possible mediator. 242 73

T-cell-replacing factor (TRF) is a T-cell-derived factor required for terminal differentiation of activated B cells to immunoglobulin-secreting cells. Previous studies have shown that a murine T-cell hybrid (B151K12) produces factor(s) that (i) induce immunoglobulin secretion by the B-cell leukemia line BCL1 and secondary anti-2,4-dinitrophenyl IgG synthesis in vitro by dinitrophenyl-primed B cells (TRF activity) and (ii) cause proliferation of the BCL1 cells [B-cell growth factor II (BCGF-II) activity]. Both activities appear to be associated with the same molecule. Here we report the production of a monoclonal antibody to murine TRF. The monoclonal antibody, designated TB13, strongly inhibited both TRF and BCGF-II activities and absorbed TRF- as well as BCGF-II-active molecules produced by B151K12 and by Xenopus oocytes that had been injected with mRNA transcribed from plasmid pSP6K-mTRF23. Inhibition was linearly dependent on the concentration of both TB13 and TRF. Monoclonal antibody TB13 did not inhibit the activities of B-cell stimulatory factor 1, interleukin 1, interleukin 2, or interleukin 3. TRF activity in dissolved samples of immunoprecipitates obtained with TB13 was recovered after NaDodSO4/PAGE, in the fractions corresponding to a protein band at Mr 46,000. Our results indicate that monoclonal antibody TB13 recognizes a molecule that has both TRF and BCGF-II activities.
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PMID:Production of a monoclonal antibody useful in the molecular characterization of murine T-cell-replacing factor/B-cell growth factor II. 244 25


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