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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neutropenia-related morbidity and mortality occurring after autologous bone marrow transplantation (ABMT) is increased by marrow purging procedures. While phase I through III clinical trials showed the enhancing activity of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on neutrophil recovery after ABMT with unpurged marrow, controversial results have been reported when purged marrow was used. Therefore, it was the aim of the present study to evaluate the efficacy of rhGM-CSF administration in a group of patients (n = 15) with lymphoid malignancies transplanted in complete remission with mafosfamide-purged (n = 10) or unpurged (n = 5) marrow. Mafosfamide concentrations used for marrow purging were evaluated on an individual basis by means of a recently described technique that destroys the granulocyte-macrophage (granulocyte-macrophage colony-forming units [CFU-GM]) compartment, but spares 50% of the more primitive stroma adherent colony-forming cells (CFU-Blast). rhGM-CSF (10 micrograms/kg/d) was started within 24 hours of ABMT and administered in a 4-hour infusion daily until the absolute neutrophil count (ANC) reached 500 x 10(6)/L and then for 7 more days. Patients receiving mafosfamide-purged or unpurged marrow failed to show any difference in terms of median number of days required to achieve an ANC > or = 500 x 10(6) (13 v 14.0, P > .4) cells/L. As compared with retrospective controls, granulocytic recovery was reduced by a median time of 11 (P < or = .0005) and 5 (P < or = .0005) days for patients grafted with purged and unpurged marrow, respectively. The number of CFU-GM (mean +/- SD) infused per kilogram of body weight was significantly lower in patients who received purged autografts as compared with those receiving unpurged autografts (0.85 +/- 0.79 x 10(4) v 15.7 +/- 9.2 x 10(4), P < or = .0005). The dose of CFU-GM progenitors infused per kilogram of body weight did not correlate (r = .031, P > .05) with the time required to reach an ANC > or = 500 x 10(6) cells/L. The number of CFU-Blast (mean +/- SD) infused per kilogram of body weight was not significantly different between patients who received purged or unpurged autografts (5.05 +/- 2.51 x 10(3)/kg v 6.18 +/- 2.66 x 10(3)/kg, P < or = .375). A statistically significant correlation (r = -.658, P < or = .05) was observed between the number of CFU-Blast infused and the number of days required to reach an ANC > or = 500 x 10(6) cells/L.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Use of recombinant human granulocyte-macrophage colony-stimulating factor in patients with lymphoid malignancies transplanted with unpurged or adjusted-dose mafosfamide-purged autologous marrow. 142 13

The colony-promoting activities of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) and recombinant granulocyte colony-stimulating factor (rG-CSF) on primary and secondary colony formation by blast progenitors (leukemic colony-forming units [L-CFU]) from 21 patients with acute myeloblastic leukemia (AML) were examined using blast colony assay and compared to colony promotion stimulated by phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM). Recombinant GM-CSF stimulated blast colonies in 13 out of 20 cases examined (1 case not done). The magnitude of stimulation by rGM-CSF varied significantly according to the type of AML, but in general was lower than that of PHA-LCM. Blast cells of type M1 did not form any colonies with rGM-CSF, although numerous colonies were produced with PHA-LCM. Type M4 blasts formed fairly large numbers of colonies, though slightly less than those stimulated by PHA-LCM. Blasts of type M2 and M5 formed colonies with the stimulation of rGM-CSF, but the numbers were considerably smaller than type M4 and those stimulated with PHA-LCM. Recombinant G-CSF stimulated blast colonies in only 5 out of 21 cases, 3 of them being type M2. The number of cases responding to rG-CSF was significantly smaller than that responding to rGM-CSF, and even in cases in which colonies were formed, the magnitude of stimulation was minimal. From these results it seems likely that blast cells of different types of AML require a different kind of CSF for their optimal growth; type M4 blasts responded to the stimulation of rGM-CSF well, but blasts of other types of AML responded poorly. Thus, except for type M4, CSF(s) other than rGM-CSF seems to be required for the sufficient growth of L-CFU. Recombinant G-CSF is not likely to play an essential role in the proliferation of leukemic blasts of most types. Previous exposure to rGM-CSF and rG-CSF did not alter the self-renewal capacity, cellular phenotype, and morphology of colony cells, indicating that the direction and degree of differentiation of L-CFU stimulated by rGM-CSF or rG-CSF were not different from those stimulated with PHA-LCM.
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PMID:Effect of recombinant GM-CSF and recombinant G-CSF on colony formation of blast progenitors in acute myeloblastic leukemia. 278 49

We studied the effects of murine recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) on murine hemopoiesis in methylcellulose culture. The GM-CSF was purified from cultures of Saccharomyces cerevisiae transfected with a cloned murine GM-CSF cDNA. In cultures of spleen cells from normal mice, only granulocyte-macrophage (GM) colonies were supported by GM-CSF. Blast cell colonies were the predominant type in cultures of spleen cells from 5-fluorouracil (5-FU)-treated mice. Dose-response studies revealed that maximal GM and blast cell colony formation is achieved with 100 U/ml GM-CSF. Blast cell colonies revealed variable but high replating efficiencies, and the secondary colonies included multilineage colonies. Serial replating of washed blast cell colonies in cultures with GM-CSF provided evidence for the direct effects of GM-CSF on the proliferation of multipotential blast cells. A combination of GM-CSF and interleukin-3 (IL-3) did not increase the number of blast cell colonies over the level supported by IL-3. This observation indicates that the progenitors for blast cell colonies that responded to GM-CSF are a subpopulation of multipotential progenitors that are supported by IL-3. Cytological studies of colonies derived from GM-CSF and/or IL-3 suggest that the eosinophilopoietic ability of murine GM-CSF is less than that of IL-3.
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PMID:Recombinant murine granulocyte-macrophage (GM) colony-stimulating factor supports formation of GM and multipotential blast cell colonies in culture: comparison with the effects of interleukin-3. 329 86

Blast cells from 70% of patients with acute myeloid leukemia (AML) show some evidence of in vitro autonomous growth, which appears to be related to the autocrine secretion of growth factors, particularly granulocyte-macrophage colony-stimulating factor (GM-CSF). In the majority of cases, the growth factors appear to be involved in classical extracellular autocrine or paracrine loops with neutralizing antibodies to the relevant cytokine inhibiting growth. In a minority, however, antibodies do not inhibit growth despite evidence of secretion of the cytokine. There is evidence for intracellular autocrine loops in murine leukemic cell lines. In this study, we wished to investigate for the presence of such intracellular loops involving GM-CSF in AML blast cells. Blast cells from 11 patients with AML were cultured in the presence of either neutralizing GM-CSF antibody or an antisense oligonucleotide directed against GM-CSF. We also studied the effect of the oligonucleotide on the autonomous growth of cells whose production of GM-CSF had been apparently abolished by either interleukin-1 receptor antagonist (IL-1Ra) or following blast cell purification using the CD34 antigen. The autonomous growth of the blast cells from nine of the 11 patients was inhibited by the antisense oligonucleotide (but not by the control sense oligonucleotide). However, only six of the nine were inhibited by the anti-GM-CSF antibody. Similarly, in one patient whose CD34 purified blast cells continued to show a high degree of autonomous growth but did not produce detectable GM-CSF, growth was inhibited by the antisense oligonucleotide but not by antibody, while in another patient whose cells were inhibited by IL-1Ra with, again, loss of detectable GM-CSF, growth could be further inhibited by the addition of the oligonucleotide but not the antibody. These studies provide evidence that intracellular autocrine loops involving GM-CSF are involved in the autonomous growth of some AML blast cells.
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PMID:Evidence for internal autocrine regulation of growth in acute myeloblastic leukemia cells. 751 89

Blast cells from up to 70% of patients with acute myeloblastic leukemia (AML) exhibit a variable degree of autonomous growth in vitro which is related to the production of autocrine growth factors including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-1) and interleukin-6 (IL-6). Approximately 40% of AML blasts with autonomous growth have been reported to exhibit abnormalities of retinoblastoma (Rb) protein expression. As the Rb protein is a known transcriptional repressor of the IL-6 promoter, we have investigated the relationship between absence of Rb protein and cytokine gene expression in AML. Blasts from 28 patients were studied, 19 were Rb protein positive by Western blot and by flow cytometry for nuclear Rb protein; blasts from nine patients were Rb-negative. Of the 28 specimens tested by RT-PCR, 24 were positive for GM-CSF mRNA, 21 for IL-1 beta mRNA, and 14 for IL-6 mRNA. Only the expression of IL-6 was found to be significantly associated with loss of Rb protein expression (p < 0.02). The relationship between Rb protein and IL-6 expression was further studied by suppressing Rb protein expression with antisense oligonucleotides. In three out of seven blasts so treated, IL-6 mRNA was induced following antisense treatment whereas control sense oligonucleotides had no effect. Blasts from four patients which secreted high levels of IL-6 exhibited in vitro autonomous growth which could be partially suppressed by anti-IL-6. These results suggest that deletion of Rb protein expression is a mechanism that can dysregulate IL-6 expression in leukemic blasts and thus potentiate the autonomous growth of these cells.
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PMID:Absence of retinoblastoma protein expression results in autocrine production of interleukin-6 and promotes the autonomous growth of acute myeloid leukemia blast cells. 796 42

Blast cells derived from peripheral blood of patients with acute myelogenous leukaemia (AML) were cultured in vitro and interleukin 1 receptor antagonist (IL1RA) concentrations determined in culture supernatants. AML blasts derived from patients classified as AML-M4 and AML-M5 subtype showed an increased release of IL1RA. IL1 alpha and IL1 beta caused a similar increase in AML blast release of IL1RA, and addition of anti-IL1 antibodies decreased IL1RA release. IL1RA release from AML blasts was also increased by stem cell factor, tumour necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor, whereas interleukin 3, interleukin 6, leukaemia inhibitory factor and granulocyte colony-stimulating factor did not significantly alter IL1RA release. When investigating IL1RA serum levels, serum concentrations were decreased in acute leukaemia patients with chemotherapy-induced cytopenia compared with healthy controls. Serum levels of both IL1RA as well as IL1 beta and soluble TNF alpha receptors increased when the leucopenic patients developed complicating bacterial infections.
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PMID:Interleukin 1 receptor antagonist (IL1RA) in acute leukaemia: IL1RA is both secreted spontaneously by myelogenous leukaemia blasts and is a part of the acute phase reaction in patients with chemotherapy-induced leucopenia. 869 37

Blast cells derived from patients with acute myelogenous leukemia (AML) were cultured in the presence of interleukin-13 (IL-13). IL-13 did not cause statistically significant alterations of AML blast proliferation when cells were cultured in medium alone or together with IL-4, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. In contrast, IL-13 inhibited constitutive AML blast secretion of IL-1 alpha, IL-1 beta, IL-6, tumor necrosis factor alpha, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. IL-4 caused a similar inhibition of constitutive cytokine secretion as IL-13, but IL-13 caused no additive inhibition in the presence of IL-4. In contrast to IL-4 which increased AML blast release of IL-1 receptor antagonist, IL-13 caused no significant alteration of blast release of the receptor antagonist. IL-13 inhibited cytokine secretion also in the presence of neutralizing IL-4 and IL-10 antibodies and when AML blasts were cultures in serum-free conditions. We conclude that IL-13 has a direct and nontoxic inhibitory effect on constitutive AML blast cytokine secretion.
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PMID:Effects of interleukin-13 on cytokine secretion by human acute myelogenous leukemia blasts. 875 69

Blood monocytes and CD34(+) haemopoietic progenitor cells, as well as certain leukaemic cell lines, acquire characteristics of mature dendritic cells (DC) after stimulation with calcium ionophore (CI). We studied whether the in vitro treatment of primary human acute myelogenous leukaemia (AML) cells with CI leads to differentiation towards DC. Blast cells derived from nine AML patients were cultured in the presence of either CI or an established differentiation cocktail consisting of granulocyte-macrophage colony-stimulating factor plus interleukin 4 and tumour necrosis factor-alpha for 5-7 d. Microscopic examination revealed that under both conditions, AML cells were shifted along the DC pathway. In seven out of nine cases, CI-cultivation led to a higher proportion of cells with dendritic morphology. The percentage of CD40 and CD86 expressing cells was significantly increased upon CI treatment compared with cytokine-cultured cells. DC molecules as CD80 and CD83 were up-regulated upon calcium mobilization of AML cells in four out of nine samples. In four cases, CI-treated stimulator cells induced an enhanced proliferative allogeneic T-cell response compared with cytokine-treated stimulator cells. In conclusion, these data demonstrate that CI treatment is an alternative in vitro strategy to differentiate human AML cells into DC.
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PMID:Calcium ionophore: a single reagent for the differentiation of primary human acute myelogenous leukaemia cells towards dendritic cells. 1152 71