Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

Thrombopoietin (TPO) is a novel hematopoietic growth factor that was cloned as a ligand for c-mpl proto-oncogene. The c-mpl proto-oncogene is expressed on various types of human leukemia cell lines derived from erythroid, megakaryocytic, and stem-cell leukemia cells. Also, c-mpl mRNA is detectable on blast cells in about half of acute myeloblastic leukemia (AML) cases regardless of French-American-British (FAB) classification. In the cases with myelodysplastic syndrome, c-mpl is expressed in a substantial fraction of refractory anemia with excess of blast (RAEB), RAEB in transformation, and chronic myelomonocytic leukemia cells, but not in refractory anemia or sideroblastic anemia. Little or no expression of c-mpl mRNA is observed in human lymphoid cell lines and blast cells of acute lymphoblastic leukemia cases. The in vitro treatment of AML cells with TPO resulted in proliferation in about 70% of c-mpl-positive AML cases. The proliferative responses of AML cells to TPO were observed not only in M7-type, but also in the other subtypes of AML cases. Furthermore, the TPO-induced proliferation of AML cells was augmented by the addition of the other hematopoietic growth factors such as interleukin-3 (IL-3), IL-6, stem cell factor, or granulocyte-macrophage colony-stimulating factor. In addition to proliferation, TPO appeared to induce megakaryocytic differentiation in a small part of AML cells. These results suggested that TPO/c-mpl system might contribute, at least in part, to abnormal growth and differentiation of AML cells.
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PMID:The effects of thrombopoietin on the growth of acute myeloblastic leukemia cells. 903 Oct 83

This randomized, placebo-controlled trial was designed to assess the efficacy and safety of therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (epoetin alfa) in anemic, neutropenic patients with myelodysplastic syndrome. Sixty-six patients were enrolled according to the following French-American-British classification: refractory anemia (20), refractory anemia with excess blasts (35), refractory anemia with ringed sideroblasts (9), and refractory anemia with excess blasts in transformation (2). Patients were stratified by their serum erythropoietin levels (less than or equal to 500 mU/mL, n = 37; greater than 500 mU/mL, n = 29) and randomized, in a 2:1 ratio, to either GM-CSF (0.3-5.0 microg/kg.d) + epoetin alfa (150 IU/kg 3 times/wk) or GM-CSF (0.3-5.0 microg/kg.d) + placebo (3 times/wk). The mean neutrophil count rose from 948 to 3831 during treatment with GM-CSF +/- epoetin alfa. Hemoglobin response (increase greater than or equal to 2 g/dL, unrelated to transfusion) occurred in 4 of 45 (9%) patients in the GM-CSF + epoetin alfa group compared with 1 of 21 (5%) patients with GM-CSF + placebo group (P = NS). Percentages of patients in the epoetin alfa and the placebo groups requiring transfusions of red blood cells were 60% and 92%, respectively, for the low-endogenous erythropoietin patients and 95% and 89% for the high-endogenous erythropoietin patients (P = NS). Similarly, the average numbers of units of red blood cells transfused during the 12-week study in the epoetin alfa and the placebo groups were 5.9 and 9.5, respectively, in the low-endogenous erythropoietin patients and 9.7 and 8.6 in the high-endogenous erythropoietin patients (P = NS). GM-CSF +/- epoetin alfa had no effect on mean platelet count. Treatment was well tolerated in most patients, though 10 withdrew from the study for reasons related predominantly to GM-CSF toxicity. (Blood. 2000;95:1175-1179)
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PMID:Effect of recombinant human erythropoietin combined with granulocyte/ macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome. GM/EPO MDS Study Group. 1066 87

The colony stimulating activities (CSAs) of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), recombinant granulocyte colony-stimulating factor (rG-CSF) and recombinant interleukin-3 (rIL-3) on blast cells from various types of acute myeloblastic leukemia (AML) patients were studied using an in vitro blast colony assay. The stimulatory magnitude of rGM-CSF was highest in type M4 blasts but almost non-existent in type M1 blasts. Some preferential stimulatory action of rG-CSF was observed in type M2, M4 blasts and in overt leukemia in patients with refractory anemia with excess of blasts. On the other hand, the stimulatory activity of rIL-3 did not differ much with the AML subtype. Exposure to rGM-CSF, rG-CSF or rIL-3 did not alter the cellular phenotype or morphology of the leukemic blasts or the self-renewal capacity of blast progenitors. Simultaneous addition of rGM-CSF, rG-CSF and rIL-3, in various combinations, produced variable results and a simple additive effect was seen in 40% of the cases studied and either a significantly larger or smaller value in the remaining cases. Recombinant GM-CSF, rG-CSF and rIL-3 when added together did not reconstitute CSA of phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM).
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PMID:Colony Stimulating Activities of GM-CSF, G-CSF and IL-3 on Blast Progenitors from Acute Myeloblastic Leukemia. 2745 45


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