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

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

Injection of a single dose of recombinant human interleukin-1 alpha (r-hu-IL-1 alpha) into mice 24 hr after 5-fluorouracil (FU) treatment resulted in an increased rate of recovery of three types of colony-forming cells (CFCs) in the bone marrow. Myeloid progenitors with high proliferative potential (responsive to CSF-1 + IL-3 + IL-1 alpha), low proliferative potential (responsive to CSF-1), megakaryocyte progenitors, and total nucleated cells per femur increased up to 5-fold, 7-fold, 3-fold, and 3-fold, respectively, in a dose related fashion compared with the control FU treated marrows. The kinetics of FU kill and recovery of these CFCs are shown.
Leukemia 1989 Dec
PMID:In vivo effects of interleukin-1 alpha on regenerating mouse bone marrow myeloid colony-forming cells after treatment with 5-fluorouracil. 268 78

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 characteristics and clinical uses of recombinant colony-stimulating factors (CSFs) are described, and the pharmacist's role as a consultant and educator on biotherapeutic substances is discussed. CSFs stimulate the formation and differentiation of the erythrocytes, neutrophils, eosinophils, basophils, monocytes, and platelets that compose the blood cell population. Recombinant CSFs represent a means by which the numbers of hematopoietic cells can be modulated, thus making these agents potentially useful in treating hematologic and immunologic deficiencies. CSFs also can increase the ability of neutrophils and monocyte-macrophages to protect the body against foreign invasion. Granulocyte macrophage colony-stimulating factor (GM-CSF) has increased host defenses in acquired immunodeficiency syndrome patients with Kaposi's sarcoma; increased neutrophil, platelet, and erythrocyte counts in preleukemic patients; and increased neutrophil counts in patients with aplastic anemia. GM-CSF and granulocyte colony-stimulating factor (G-CSF) have appeared to alleviate the drastic decrease in neutrophil counts associated with cytotoxic chemotherapy. G-CSF also has shown promise in stimulating neutrophil production in patients with transitional cell carcinoma, congenital agranulocytosis, and hairy-cell leukemia. Mild adverse effects such as fever, chills, rash, fatigue, myalgia, and bone pain are associated with GM-CSF therapy; G-CSF therapy is associated mostly with mild to moderate bone pain. Areas of education for pharmacists working with biotherapeutic substances include stability, storage temperature, drug interactions, novel drug-delivery systems such as monoclonal antibodies or liposomes, variations in biologic activity, and the evolving nature of the information about these investigational drugs. The pharmacist can anticipate an increasing role as a consultant on the use of CSFs and other biotherapeutic substances.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Colony-stimulating factors and tomorrow's pharmacy: why we must be ready. 269 Jun 7

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

The c-fms proto-oncogene encodes the receptor for the mononuclear phagocyte colony stimulating factor, CSF-1. Although the tyrosine kinase activity of the CSF-1 receptor is stimulated by its ligand, the viral oncogene, v-fms, encodes a constitutive receptor kinase that can transform both fibroblasts and hematopoietic cells by a nonautocrine mechanism. Mutations in the c-fms gene as well as a critical alteration of the distal 3' coding sequences appear to be responsible for fully activating its latent transforming potential. The v-fms gene can convert CSF-1 or IL-3 dependent hematopoietic cell lines to factor independence and render them tumorigenic. Expression of the v-fms gene product does not transmodulate the normal receptors for CSF-1 or IL-3 and affects neither their affinity, number, nor potential to be independently down-regulated by their ligands or by phorbol esters. The ability of v-fms to transform hematopoietic target cells suggests that critical alterations in the c-fms proto-oncogene might similarly contribute to leukemia.
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PMID:Fibroblast and hematopoietic cell transformation by the fms oncogene (CSF-1 receptor). 282 35

Treatment of HL-60 leukemia cells with the inducers of differentiation dimethyl sulfoxide (DMSO) and 6-thioguanine (TG) reduces the proliferative capacity of the cells. DMSO acted in a serum-independent manner and reversibly inhibited competence to enter S phase after 24 h of treatment. Purified human granulocyte-macrophage colony-stimulating factor (GM-CSF) but not human CSF-1, restored S phase competence and growth of DMSO-treated cells over a 7-day period. GM-CSF had no effect on the saturation density of control cells, even under conditions of reduced growth. Furthermore, GM-CSF antagonized the growth inhibitory actions of TG associated with cytodifferentiation but not those associated solely with TG cytotoxicity. The number of high affinity, cell surface GM-CSF receptors doubled after treatment of HL-60 cells with DMSO for 24 h and reached a maximum 4- to 5-fold increase within 72 h of exposure. The Kd of GM-CSF binding, 240 pM, was comparable to the concentration required to elicit a mitogenic response in DMSO-treated cells. An HL-60 variant that had been selected for resistance to TG-induced growth inhibition and differentiation (R. E. Gallagher et al., Cancer Res., 44: 2642-2653, 1984) was found to have less than 20% of the cell surface GM-CSF receptors when compared to either wild type cells, or a variant line selected for resistance to TG cytotoxicity. These studies demonstrate that HL-60 cells undergoing differentiation simultaneously lose autonomous growth properties and acquire cell surface growth factor receptors and mitogenic responsiveness.
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PMID:Enhanced mitogenic responsiveness to granulocyte-macrophage colony-stimulating factor in HL-60 promyelocytic leukemia cells upon induction of differentiation. 283 46

The macrophage colony stimulating factor, CSF-1 (M-CSF) exerts its pleiotropic effects on hematopoietic cells of the mononuclear phagocyte series by binding to a single class of high affinity receptors encoded by the c-fms proto-oncogene. Binding of CSF-1 to its receptor activates an intrinsic tyrosine kinase activity, resulting in autophosphorylation of the receptor on tyrosine, rapid receptor down modulation, and phosphorylation of as yet unidentified physiologic substrates that initiate a mitogenic response. Transduction of a human CSF-1 receptor cDNA into mouse fibroblasts enables them to proliferate in response to human recombinant CSF-1, suggesting that the receptor gene contains all the information necessary to elicit a mitogenic response, even in cells which do not normally respond to the growth factor. The v-fms oncogene product has undergone genetic alterations which constitutively activate the receptor kinase in the absence of CSF 1. Insertion of the v-fms gene into macrophage or immature myeloid cell lines abrogates their dependence on hematopoietic growth factors and renders them tumorigenic in nude mice. Reconstitution of lethally irradiated mice with bone marrow stem cells containing the v-fms oncogene also induces clonal proliferation and, ultimately, frank malignancies of multiple hematopoietic lineages. Thus, constitutive activation of the CSF-1 receptor gene, either by mutation or gene rearrangement, might be expected to contribute to leukemia.
Leukemia 1988 Dec
PMID:The role of the CSF-1 receptor gene (C-fms) in cell transformation. 284 91

Southern blot analysis of various genes was used to compare the human promyelocytic leukemia cell line HL-60 and the BII cell line, which reportedly arose as a spontaneous differentiation inducer-resistant variant from an HL-60 culture. Granulocyte-macrophage colony stimulating factor gene restriction fragment polymorphism, due to a partial deletion of one of the alleles of this gene in HL-60, was not observed in the BII cells. Furthermore, the p53 oncogene, most of which is deleted in the HL-60 cell line, was found to be intact in the BII cell line. Human leukocyte antigen typing revealed that the two cell lines shared the A locus but differed at the B locus. Several unique restriction fragments hybridizing to human leukocyte antigen class I and DR beta gene probes were observed in the DNA digests of each cell line. Altogether these data provide definitive evidence that BII represents a human cell line of different origin than HL-60. Further lineage determination of this cell line could add a useful member to the group of leukemic cell lines.
Leukemia 1987 Feb
PMID:Southern blot analysis of BII cell line--a putative variant of HL-60. 288 53

Three mouse genomic domains, Fim1, Fim2, and Fim3, were previously described as proviral integration regions frequently involved in the early stages of myeloblastic leukemogenesis induced in vivo or in vitro by the Friend murine leukemia virus. Fim2 was identified as the 5' end of the c-Fms protooncogene, which encodes the receptor of the macrophage colony stimulating factor (Csflr). The functions of Fim1 and Fim3 are not yet known, but these regions are highly conserved among different species. To examine whether these regions could correspond to known human loci involved in genetic alterations specific to some human leukemias, we undertook their chromosomal mapping. The localization of FIM2/c-FMS on 5q33 was confirmed. FIM1 and FIM3 were localized on human chromosomes 6p22.3-p23 and 3q27 respectively. Interestingly, translocations involving these two regions have been described in various hematopoietic malignancies: the t(6;9)(p23;q34) in acute nonlymphocytic leukemias and the 3q26-q28 translocations in a large variety of leukemias.
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PMID:The human homologues of Fim1, Fim2/c-Fms, and Fim3, three retroviral integration regions involved in mouse myeloblastic leukemias, are respectively located on chromosomes 6p23, 5q33, and 3q27. 292 Oct 36


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