Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to investigate the pathogenesis of juvenile chronic myelogenous leukaemia (J-CML) we examined the biosynthetic rates of G gamma and A gamma globin chains in the erythropoietic bursts from the bone marrow of a patient with J-CML. Globin chains were labelled with 14C-labelled amino acids, separated by isoelectric focusing and quantitated by fluorography. The synthesis of gamma-chains in the erythropoietic bursts comprised 89.0% of the total non-alpha-chains. The G gamma:A gamma ratio was 0.67, which is within the ratios obtained in newborns. Furthermore, individual erythropoietic bursts contained varying ratios of both gamma and beta chains and all revealed more G gamma than A gamma chain synthesis. The relative proportions of G gamma and total gamma chain biosynthesis in 62 separate erythropoietic bursts were 0.69 +/- 0.06 and 0.86 +/- 0.06, respectively. Cumulative frequency distributions of individual bursts differing in the ratios of gamma/(gamma + beta) and G gamma/(G gamma + A gamma) approached normal frequency distributions. These results suggest that the levels of Hb F in J-CML are controlled by qualitative changes in a single population of erythropoietic precursors, in which normal switching of the G gamma:A gamma ratio has not occurred, rather than by the abnormal proliferation of an F-cell clone.
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PMID:Characterization of the erythropoietic precursors (BFU-E) in a patient with juvenile chronic myelogenous leukaemia by the analysis of G gamma and A gamma globin chains. 657 13

In August, 1992, we established a leukemic cell line (NS-Meg) from a patient in megakaryoblastic transformation of Philadelphia chromosome-positive chronic myeloid leukemia. The NS-Meg cells were positive for alpha-naphthyl acetate esterase and periodic acid-Schiff (PAS) staining and for surface CD4, CD7, CD13, CD34, CD41a, and glycophorin A antigens. Ultrastructurally, the cells had alpha-granules, demarcation membranes, and platelet peroxidase activity. The NS-Meg cells spontaneously produced platelet-like particles which contained alpha-granules, mitochondria and dense bodies, strongly suggesting platelet production. Erythropoietin (Epo), granulocyte/macrophage colony stimulating factor(GM-CSF), and interleukin 3 (IL-3) promoted the growth of NS-Meg cells. Phorbol-12-myristate-13-acetate increased the expression of both CD41a and CD61 antigens. Ten-day exposure to Epo induced mature erythroblasts and red cells. These benzidine-positive cells were positive for hemoglobin F staining. Untreated NS-Meg cells expressed mRNA for the Epo receptor (EpoR), for GATA-1, and for alpha 1, alpha 2 and gamma globin genes. These results indicate that NS-Meg cells undergo terminal differentiation of both megakaryocytic and erythroid lineages. This cell line should be a very useful tool for the investigation of both megakaryocytic and erythroid maturation.
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PMID:A newly established megakaryoblastic/erythroid cell line that differentiates to red cells in the presence of erythropoietin and produces platelet-like particles. 771 48

The K562 cell line has been proposed as a useful experimental system to identify anti-tumor compounds acting by inducing terminal erythroid differentiation. K562 cells exhibit a low proportion of hemoglobin-synthesizing cells under standard cell growth conditions, but are able to undergo terminal erythroid differentiation when treated with a variety of anti-tumor compounds. In this paper we report a screening study on a set of different modified C(5) uracil derivatives for the evaluation of their antiproliferative effect in connection with erythroid differentiation pathways, and for defining a new class of drug candidates for the treatment of chronic myelogenous leukemia. Activity of the derivatives tested can be classified in two effect: an antiproliferative effect linked to a high level of erythroid differentiation activity and an antiproliferative effect without activation of gamma globin genes The highest antiproliferative effect and erythroid induction was shown by compound 9, a thymine derivative bearing a n-octyl chain on nitrogen N(1), whereas thymine did not show any effect, suggesting the importance of the linear alkyl chain in position N(1). To our knowledge this compound should be considered among the most efficient inducers of erythroid differentiation of K562 cells. This work is the starting point for the quest of more effective and specific drugs for the induction of terminal erythroid differentiation, for leading new insights in the treatment of neoplastic diseases with molecules acting by inducing differentiation rather than by simply exerting cytotoxic effects.
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PMID:C(5) modified uracil derivatives showing antiproliferative and erythroid differentiation inducing activities on human chronic myelogenous leukemia K562 cells. 2195 70