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)

A new human leukemia cell line with megakaryocytic features, designated UT-7, was established from the bone marrow of a patient with acute megakaryoblastic leukemia. Surface marker analysis revealed that the majority of the cells reacted with monoclonal antibodies against platelet glycoprotein Ib (CD42b), glycoprotein IIb/IIIa (CD41a), MY 7 (CD13), MY 9 (CD33), and glycophorin A antigens. Cytogenetic analysis showed a human male near-tetraploid karyotype with a modal chromosome number of 92-96. Flow cytometry-derived DNA histograms demonstrated that the majority of the cells spontaneously contained 4 N DNA ploidy levels. Ultrastructural study showed that platelet peroxidase activity was weakly positive but myeloperoxidase activity was negative. Ferritin and theta-granule, which have been used as ultrastructural markers for the erythroid lineage, could not be detected. In response to phorbol myristate acetate, platelet factor 4 and beta-thromboglobulin, which were specifically synthesized in the process of megakaryocyte maturation, dramatically increased in UT-7 cells. This was accompanied by an increase in cell size, ploidy level, platelet peroxidase activity, and the surface density of glycoprotein IIb/IIIa antigen. These findings suggest that UT-7 is a new leukemic cell line with megakaryocytic features and with the potential to differentiate into cells with more mature megakaryocytic properties in response to phorbol myristate acetate. This cell line showed strict dependency on interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor, or erythropoietin. The maximal effective doses of IL-3, granulocyte-macrophage colony-stimulating factor, and erythropoietin for proliferation in liquid culture were 10 units/ml, 1 ng/ml, and 1 unit/ml, respectively. These concentrations were comparable to the doses that maximally stimulate the clonal growth of normal hemopoietic cells. IL-6 could stimulate the proliferation of UT-7 cells but not maintain the line in long-term culture. UT-7 cells may be a useful model for (a) the analysis of gene regulation of megakaryocytic maturation-associated proteins expressed in the process of megakaryocytic differentiation and (b) the study of signal transduction of hemopoietic factors associated with megakaryocytopoiesis.
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PMID:Establishment and characterization of a human leukemic cell line with megakaryocytic features: dependency on granulocyte-macrophage colony-stimulating factor, interleukin 3, or erythropoietin for growth and survival. 182 23

A new human myeloid cell line has been established recently from the bone marrow cells of a patient with chronic myelogenous leukemia in blast crisis. The active proliferation and survival of the cells in RPMI 1640 medium containing fetal calf serum are clearly dependent on the presence of either natural or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Despite permanent culturing in rhGM-CSF (100 U/mL), the cells do not differentiate and bear the myelomonocytic surface markers CD34, CD13, CD36, as well as HLA-DR, but not CD3, CD7, CD10, CD11b, CD14, CD20, or CD42b. The predominant karyotype, apart from tetraploidy in several cells, is 45, XX, -9, -17, -19, -22, 7p-, 9q+ (der t[9;22]), der (13q), with three additional marker chromosomes, from which one was observed in the patient's leukemic cells. On BglII-digested DNA, Southern blot analysis with bcr 5' as the probe detected two additional hybridizing restriction fragments of 8.6 and 11.0 kilobase pairs.
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PMID:Establishment and characterization of a granulocyte-macrophage colony-stimulating factor-dependent human myeloid cell line. 219 61

Thrombopoietin (TPO) is the major regulator of growth and differentiation of megakaryocytes. To identify functionally important regions in the cytoplasmic domain of the TPO receptor, mpl, we introduced wild-type mpl and deletion mutants of murine mpl into the granulocyte-macrophage colony-stimulating factor (GM-CSF)- or erythropoietin (EPO)-dependent human cell line UT7. TPO induced differentiation of UT7-Wtmpl cells, not parental UT7 cells, along the megakaryocytic lineage, as evidenced by decreased proliferation, changes in cell morphology, and increased surface expression and mRNA levels of megakaryocytic markers CD41, CD61, and CD42b. When UT7-mpl cells were cultured long-term in EPO instead of GM-CSF, the TPO effect was dominant over that of EPO. Moreover, the differentiation induced by TPO was more pronounced for cells shifted from EPO to TPO than for cells shifted from GM-CSF to TPO, as shown by the appearance of polyploid cells. Mutational analysis of the cytoplasmic domain of mpl showed that proliferation and maturation functions of mpl can be uncoupled. Two functional regions were identified: (i) the first 69 amino acids comprising the cytokine receptor motifs, box I and box 2, which are necessary for both TPO-induced mitogenesis and maturation; and (ii) amino acids 71 to 94, which are dispensable for proliferation but required for differentiation. Surprisingly, however, EPO could complement this latter domain for TPO-induced differentiation, suggesting a close relationship between EPO and TPO signaling.
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PMID:Functional regions of the mouse thrombopoietin receptor cytoplasmic domain: evidence for a critical region which is involved in differentiation and can be complemented by erythropoietin. 862 15