Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction of colony-stimulating factors (CSF) and retinoic acid (RA) in the proliferation and differentiation of HL-60 cells was examined. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated the proliferation of HL-60 cells in a dose-dependent manner at concentrations of 0.01-100 ng/ml; however, the proliferation due to GM-CSF was suppressed by 100 nM RA. Granulocyte colony-stimulating factor (G-CSF) slightly stimulated the proliferation of HL-60 cells at concentrations above 10 ng/ml. Neither G-CSF nor GM-CSF alone induced 12-o-tetra-decanoyl-phorbol-13-acetate (TPA)- or N-formyl-methionyl-phenylalanine (FMLP)-stimulated nitro-blue tetrazolium (NBT) reduction at concentrations of 0.01-100 ng/ml. G-CSF induced TPA- and FMLP-stimulated NBT reduction in the presence of 100 nM RA, but GM-CSF induced only TPA-stimulated NBT reduction. RA in addition to G-CSF synergistically increased FMLP binding to HL-60 cells, accompanied by increased NBT reduction in response to FMLP. RA in addition to GM-CSF markedly increased FMLP binding to HL-60 cells more than that induced by RA alone, but the combined treatment with RA and GM-CSF did not increase FMLP-stimulated NBT reduction more than that induced by RA alone. The results suggest that G-CSF stimulates RA-induced morphological and functional differentiation of HL-60 cells, but the differentiation-enhancing effects of GM-CSF are limited, whereas the growth-stimulating effect of GM-CSF on HL-60 cells is greater than that of G-CSF.
Leukemia 1991 Jan
PMID:Granulocyte colony-stimulating factor, not granulocyte-macrophage colony-stimulating factor, co-operates with retinoic acid on the induction of functional N-formyl-methionyl-phenylalanine receptors in HL-60 cells. 170 36

The regulation of haemopoiesis in myelodysplastic syndromes (MDS) was evaluated by measuring and comparing the in vitro response of marrow progenitors from 18 MDS patients to stimulation with recombinant haemopoietic growth factors (HGFs), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF) and interleukin-3 (IL-3). A similar pattern of colony growth was detected with all three HGFs in most MDS patients, exhibiting subnormal growth of GM-CFU and markedly poor to absent growth of BFU-E and CFU-GEMM. A common severe impairment in the growth of all colony types with all three HGFs was observed in five patients, four of whom presented with pancytopenia. The stimulation of MDS marrow progenitors with a five-fold higher than control saturating dose of HGFs induced a significant increase in the frequency of one, two, or all three colony types in cultures of 14 patients, whereas colony numbers in control (n = 8) marrow cell cultures were not significantly changed. All four of the non-responders were pancytopenic and three exhibited markedly impaired colony growth. Supersaturating GM-CSF, G-CSF and IL-3 increased GM-CFU numbers in six, three, and three patients, respectively. The values for BFU-E were three, six, and seven and for CFU-GEMM two, one, and five. The enhancement of MDS marrow colony numbers by supersaturating HGFs which exert their effects directly or via the action of marrow accessory cells, suggests that the progenitor cell growth abnormalities in these disorders may involve a defect in the capacity of accessory and/or progenitor cells to respond to stimulation with specific haemopoietic growth regulators.
Leukemia 1991 Apr
PMID:Impaired response of myelodysplastic marrow progenitors to stimulation with recombinant haemopoietic growth factors. 170 45

The effects of human recombinant colony-stimulating factors (r-CSFs), interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) on inducing the growth of colonies derived from patients with acute myeloid leukemia (AML) (CFU-L) were investigated and compared to the proliferative response of CFU-GM derived from highly enriched normal blast cell populations. The effects of GM-CSF and IL-3 alone were similar. Both only minimally stimulated normal colonies derived from CFU-GM when compared to stimulation with MoCM (a mean of 28% of the total colonies and 17% of the colonies greater than 100 cells obtained with MoCM). Similarly, the number of leukemic colonies was substantially less than with MoCM (less than 30% of MoCM) in all but 3/10 AML patients and both were only able to significantly stimulate CFU-L derived colonies greater than 50 cells from 2/10 patients. G-CSF alone stimulated some CFU-L derived colony growth in 9/10 patients but the number stimulated was minimal relative to MoCM in five of the patients and significant stimulation of colonies greater than 50 cells occurred in only one patient. The mean number of normal CFU-GM derived colonies stimulated by G-CSF was 41% of the total colonies and 34% of the colonies greater than 100 cells generated by MoCM. The combination of G-CSF with GM-CSF and G-CSF with IL-3 resulted in a synergistic or additive increase in the number of CFU-L in 5/10 and 7/10 patients, respectively, and a synergistic increase in the size of CFU-L in 5/10. The same combinations resulted in a significant synergistic effect on size of normal CFU-GM derived colonies. There was no evidence of a synergistic increase in the number or size of CFU-L and CFU-GM derived colonies stimulated with GM-CSF in combination with IL-3. In addition, a combination of all three (G-CSF + GM-CSF + IL-3) did not enhance the effect of G-CSF + GM-CSF or G-CSF + IL-3. These results suggest that there is significant heterogeneity among AML patients in the pattern of responsiveness of the leukemic cells to the recombinant growth factors. In addition, their responsiveness does not significantly differ from that of normal progenitors. In view of the current clinical trials with r-CSFs and cytotoxic drugs in AML patients, this issue is important and worthy of further investigation.(ABSTRACT TRUNCATED AT 400 WORDS)
Leukemia 1991 May
PMID:Proliferative response of human acute myeloid leukemia cells and normal marrow enriched progenitor cells to human recombinant growth factors IL-3, GM-CSF and G-CSF alone and in combination. 170 11

The myelodysplastic syndromes are clonal hematopoietic stem cell disorders characterized by varying degrees of pancytopenia and often a progression to acute myeloid leukemia. Recent evidence has linked myelodysplastic syndromes to environmental and occupational genotoxic exposure. Specific cytogenetic abnormalities are well described in myelodysplastic syndromes and have been demonstrated to be useful diagnostic and prognostic tools. Activation of protooncogenes such as ras and fms have also been noted in myelodysplastic syndromes; however, their contribution to the pathogenesis of the syndrome remains to be determined. Aggressive leukemia-like induction therapy, differentiating agents (low-dose cytarabine, 13-cis-retinoic acid) have had little impact on overall survival in myelodysplastic syndromes. The recombinant hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor) may be of significant benefit to patients with myelodysplastic syndromes, although it remains to be determined whether they will have a substantial impact on survival. Allogeneic bone marrow transplantation is the only potentially curable treatment of myelodysplastic syndromes. The advanced age of these patients as well as the lack of histocompatible donors restricts this modality to only a small proportion of patients.
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PMID:Recent advances in biology and treatment of myelodysplasia. 171 May 5

The effects of the inhibitor for protein kinase A or C, or tyrosine kinase (H-8, staurosporine, or genistein, respectively) on the proliferation of leukemic and normal bone marrow cells stimulated by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), or interleukin-3 (IL-3) were studied using the MTT assay. These inhibitors suppressed the proliferation of leukemic and normal bone marrow cells in a dose-dependent manner. Although the suppressive effect of each inhibitor on cell proliferation was varied in each instance, the effects were almost similar whichever CSF was added. A significant difference was not recognized between leukemic and normal bone marrow cells in terms of sensitivity to these inhibitors. The data indicate that protein kinase inhibitors have an inhibitory effect on leukemic and normal hematopoietic cell proliferation and that further studies are required to determine if this effect is due to the inhibition of protein kinases acting as the second messenger of CSFs.
Leukemia 1991 Sep
PMID:Effect of protein kinase inhibitors on the proliferation of leukemic cells stimulated by granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor or interleukin-3. 171 9

The pathogenic human parvovirus B19 has extreme tropism for human erythroid progenitor cells and has resisted cultivation in conventional cell lines. We report first propagation of this virus in an erythropoietin-dependent strain of a megakaryoblastic leukemia cell line called UT-7. Virus protein was present in about 5% of cells after 1 week of culture. Appropriate ratios of major and minor capsid proteins were determined by immunoblot, and newly synthesized capsid protein was detected by immunoprecipitation of radioactively labeled cell lysates. High molecular weight monomer and dimer intermediates were detected by Southern analysis, indicating active viral replication. Approximately 1,000 genome copies were present per infected cell, and at the optimal multiplicity of infection 20- to 50-fold more virus was produced than inoculated. Virus propagation only occurred in UT-7 cells that were adapted to growth in erythropoietin; virus signal was not detected in UT-7 cells adapted for growth in granulocyte-macrophage colony-stimulating factor or interleukin-3, even with exposure to erythropoietin for several days. Infectious virus was detected in cultures as long as 3 months after inoculation. Despite persistence, there was no evidence of viral integration on Southern analysis. This cell line may prove useful for the production of infectious virus and in the analysis of B19 parvovirus persistence, cytotoxicity, and permissivity.
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PMID:First continuous propagation of B19 parvovirus in a cell line. 172 7

The K562 cell line provides a unique population of primitive human myeloid leukaemia cells which can be induced to differentiate along the erythroid, granulocytic, macrophage and megakaryocytic lineages in response to several agents. Cytarabine is not only the most widely used drug in the treatment of myeloid leukaemia but also the most effective agent in K562 cells. The effects of five recombinant human cytokines - interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-alpha, interferon-beta and interferon-gamma on cytarabine-induced growth inhibition and differentiation of K562 cells was studied in liquid suspension cultures. GM-CSF and to a lesser extent IL-3 enhanced the antiproliferative effect of cytarabine in K562 cells, whereas the three interferons reduced it. The efficacy of cytarabine in inhibiting the growth of K562 cells was doubled by its combination with GM-CSF or IL-3 but was halved by its combination with interferons. The five cytokines did not significantly affect cytarabine-induced erythroid differentiation of K562 cells. The present results appear to favour the use of GM-CSF and IL-3 but not of interferons in future treatment strategies based on a combined cytokine and chemotherapy approach for myeloid leukaemia.
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PMID:Effects of recombinant human cytokines on cytarabine activity in K562 human myeloid leukaemia cells. 176 Sep 44

The mechanism by which the human T-cell leukemia viruses type I and II (HTLV-I and -II) transform T cells is unknown, but the nonstructural Tax protein that these viruses produce is known to be essential for viral replication and to have the capacity to trans-activate cellular gene expression. The HTLV-I and -II Tax proteins have been shown to activate the promoter of both the human and mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) genes in mature T-cell lines. T-cell-specific Tax-responsive sequences were previously localized to the 90-bp region extending from base pairs -53 to +37 in the human GM-CSF promoter. In this study, a series of site-directed and deletion mutations were created in the human GM-CSF promoter, which was linked to the chloramphenicol acetyltransferase (CAT) gene, and the constructs were assayed for their response to Tax by using a Tax-expressing plasmid in transient cotransfection assays. The results demonstrated that both copies of the repeated sequence CATTA (A/T), located between base pairs -48 and -36, are required for Tax responsiveness in T cells and that these sequences bind nuclear factors present in T cells. The Tax-responsiveness of other sequences located 5' of base pair -53 was also examined, including an NF-kappa B consensus sequence and the CK1, CK2, and GC-rich regions identified in both the mouse and human GM-CSF promoters. These sequences did not have Tax-responsive regulatory activity when they were examined in the context of the intact human GM-CSF promoter in T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tax responsiveness of the GM-CSF promoter is mediated by mitogen-inducible sequences other than kappa B. 176 53

Hematopoietic growth factors (HGFs) interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) individually have been shown to increase the percentage of acute myeloid leukemia (AML) blasts in S phase and enhance the cytotoxic effects of Ara-C against these blasts in culture. We compared in vitro the effects of a combined treatment with GM-CSF (10 ng/mL) plus IL-3 (10 ng/mL) on the metabolism and cytotoxicity of Ara-C in normal bone marrow mononuclear cells (NBMMC) and AML blasts. NBMMC from six healthy volunteers and AML blasts from 10 patients were incubated for 20 hours with or without IL-3 plus GM-CSF, followed by a concurrent treatment with Ara-C for 4 additional hours. Exposure to the HGFs and Ara-C produced significantly higher intracellular Ara-CTP levels as well as higher Ara-CTP/dCTP pool ratios in AML blasts as compared with NBMMC. Treatment with HGFs resulted in [3H] Ara-C DNA incorporation that was significantly higher in AML blasts versus NBMMC. This selective improvement of Ara-C metabolism in AML blasts was associated with an enhanced Ara-C-mediated leukemia colony-forming unit (CFU) growth inhibition. In contrast, exposure to HGFs resulted in an improved colony growth of normal CFU granulocyte-monocyte and CFU-granulocyte, erythroid, monocyte, megakaryocyte. These in vitro studies indicate that a combined treatment with IL-3 plus GM-CSF may improve the selectivity of Ara-C against AML blasts.
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PMID:Treatment with interleukin-3 plus granulocyte-macrophage colony-stimulating factors improves the selectivity of Ara-C in vitro against acute myeloid leukemia blasts. 182 60

The intravenous administration of recombinant human granulocyte-macrophage colony-stimulating factor to three patients with leukemia who were receiving marrow aplasia-inducing chemotherapy resulted in the development of wide-spread erythematous macules and papules. The course of the eruption paralleled the time of infusion of the granulocyte-macrophage colony-stimulating factor. Skin biopsy specimens taken from two of the eruptions displayed characteristic changes consisting of a variable mixture of granulocytes and lymphocytes, increased number and size of dermal macrophages, mild to moderate epidermal exocytosis, intercellular edema, and rare dyskeratotic keratinocytes. Immunophenotypic analysis of one specimen was notable for keratinocyte intercellular adhesion molecule-1 expression. Administration of the recombinant human cytokine in pharmacologic doses is postulated to induce changes in the immunologic status of the skin, resulting in the expression of a cutaneous eruption.
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PMID:Intravenous administration of recombinant human granulocyte-macrophage colony-stimulating factor causes a cutaneous eruption. 182 45


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