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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On the basis of observations with (1) erythropoietin induced erythroid differentiation of foetal mouse liver proerythroblasts and (2) chemically induced expression of the erythroid program in MELC, it appears that DNA replication plays a critical role in the transition to haemoglobin formation. Erythropoietin acts selectively on proerythroblasts to stimulate first housekeeping RNA species (rRNA, tRNA), then cell proliferation and differentiation. In erythro-leukemia cells expression of the erythroid program is induced by a variety of polar compounds. DNA synthesis appears requisite to this transition to haemoglobin formation, The molecular site of action of inducing compounds is not established but it is suggested that one critical effect is on the structure of chromatin which occurs during DNA replication and results in the transcription of the erythropoietic gene program.
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PMID:Erythroid differentiation and the cell cycle: some implications from murine foetal and erythroleukemic cells. 107 Feb 88

Erythropoietin level in the serum and urine of adult patients with acute leukaemia (AML, ALL, MML) was estimated by polycythaemic mouse bioassay in order to obtain more information about the associated anaemia. In AML and ALL patients the serum erythropoietin level as found to be increased and in a negative correlation with the blood haemoglobin concentration. In ALL patients erythropoietin in urine was increased regularly while in AML patients it was not. No correlation between the serum level and the urinary excretion of ESF, or between the blood Hb and the serum ESF, was found in MML patients. The results show that anaemia in leukaemia is not due to the low ESF level.
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PMID:Erythropoietin level in patients with acute leukaemia. 107 11

Friend murine leukemia virus induces splenic enlargement and an increase in RNA polymerase activity of spleen nuclei. Actinomycin D, administered at 60 mug/kg body weight/day prevents the development os splenomegaly and the elevation of polymerase activity following infection, but it has only a slight effect on the production of virus in spleen tissue. Thus, the alteration of RNA synthesis is not a result of virus proliferation, but instead may be a manifestation of leukemic erythropoiesis. Normal erythropoiesis, stimulated by erythropoietin administration, produces a similar but transient increase in RNA polymerase activity in spleen nuclei. Erythropoietin administered before, but not after, Friend virus infection results in an enhancement of RNA polymerase activity, as measured 9 days after inoculation. This effect is most simply explained by assuming that there is a common target cell pool for both erythropoietin and Friend virus, and that this pool becomes refractory to the influence of the hormone as a result of the leukemic process.
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PMID:Role of cellular RNA polymerases in virus-induced leukemogenesis. 114 21

Erythropoietin (Epo) is the major regulator of erythroid viability, proliferation, and differentiation. These functions are transduced following binding of Epo to a specific cell surface receptor, the erythropoietin receptor (EpoR), a member of a new cytokine receptor superfamily of receptors. An activating mutation in the murine EpoR has been described (cEpoR) and confers growth factor-independent growth upon an IL-3-dependent pro-B cell. To determine the effect of an activating mutation in the EpoR upon erythropoiesis specifically and hematopoiesis generally, we infected hematopoietic progenitors and mice with a recombinant erythroleukemic spleen focus-forming virus (SFFV), lacking its pathogenic env gene but expressing cEpoR (SFFVcEpoR). In vitro, infection with SFFVcEpoR resulted in factor-independent growth and development of CFU-Es yet had no effect on BFU-E growth, mixed colony growth, or myeloid colony growth. Mice infected with SFFVcEpoR, but not a virus expressing wild type EpoR (SFFVEpoR), developed erythrocytosis and splenomegaly.
Leukemia 1992
PMID:Mutation in murine erythropoietin receptor induces erythropoietin-independent erythroid proliferation in vitro, polycythemia in vivo. 131 65

Erythropoietin (Epo) gene expression was studied in a number of different haemopoietic cell lines by in situ hybridization and Northern Blot analysis using a radioisotope-labelled monkey Epo DNA probe. A positive message was expressed by a human cell line, CM-S, derived from a patient with congenital hypoplastic anemia, and by a murine erythro-leukaemic cell line, clone 707, derived from the spleen of Friend virus-infected mice. No message was detected in two megakaryoblastic cell lines, and in a monocytic cell line, derived from a patient with acute monocytic leukaemia. These data may fit with the hypothesis of expression of Epo and other growth factors by haemopoietic cells through a mechanism of so-called autocrine secretion.
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PMID:Erythropoietin gene expression in haemopoietic cell lines. 136 6

Hematological disorders are commonly complicated by anemia, and the symptoms of red cell deficiency adversely affect the quality of life. Erythropoietin is a glycoprotein which controls red blood cell production. Recombinant human erythropoietin, 50 U/kg/day, was given subcutaneously to 16 patients with myelodysplastic syndrome and anemia. All but one patient was transfusion dependent. Diverse pretreatment endogenous serum erythropoietin levels were noted and ranged from 17 to 3616 IU/l. Two patients (12.5%) demonstrated an improvement in hemoglobin levels obviating the need for transfusions. Their responses lasted 5+ and 7 months with maintenance erythropoietin treatment. The responders had endogenous serum erythropoietin levels of 44 and 170, respectively. Treatment was generally tolerated without constitutional side-effects. However, three patients developed thrombocytopenia and one developed joint pain and leukocytosis on treatment. Overall, six patients showed changes in non-erythroid cells: two patients had an increase in platelet counts; three patients, a decrease in platelet counts; and one patient, an increase in white blood cell counts. Most of these changes reversed rapidly once erythropoietin was stopped. It is concluded that (a) serum erythropoietin levels are extremely variable in anemia patients with myelodysplastic syndrome, (b) only a minority of patients benefit from treatment with recombinant human erythropoietin, and (c) erythropoietin can affect cells of the myeloid and megakaryocytic lineage in a small proportion of patients.
Leukemia 1991 Nov
PMID:Erythropoietin treatment in patients with myelodysplastic syndrome and anemia. 196 Oct 41

Erythropoietin-dependent regulation of erythropoiesis in myelodysplastic syndromes (MDS) was evaluated by measuring the in vitro response of primitive (BFU-E) and relatively mature (CFU-E) erythroid progenitors from 12 patients and from eight healthy donors to recombinant human erythropoietin (rhEPO), and by quantifying relationships between circulating EPO levels and progenitor cell frequencies in MDS marrow. Half-maximal growth of MDS CFU-E and BFU-E was detected at a 4-fold higher rhEPO concentration than required by control erythroid progenitors. Nine of the patients evaluated exhibited maximal growth of erythroid colonies at 5- to 20-fold higher than control saturating rhEPO concentrations. Circulating EPO levels in MDS patients were elevated, with a mean value approximately 35-fold higher than that of controls. The frequency of MDS marrow CFU-E and BFU-E was 57 +/- 42% and 18 +/- 9% of the mean control values, respectively. Correlation analysis of the relationships between MDS EPO levels and erythroid progenitors indicated that the anemia in MDS is not attributable to an abnormality in the capacity of EPO to induce the generation of CFU-E, but may be influenced by the BFU-E population, whose severe deficiency results in insufficient influx of EPO-responsive cells. Our findings therefore suggest that treatment of MDS patients with rhEPO may be of limited benefit, since the generation of BFU-E from more primitive ancestors and the initial growth requirements of these cells are not under the regulatory influence of this hormone.
Leukemia 1990 Nov
PMID:In vitro studies of erythropoietin-dependent regulation of erythropoiesis in myelodysplastic syndromes. 223 91

Primary polycythaemia (PP), idiopathic myelofibrosis (MF), essential thrombocythaemia (ET) and chronic granulocytic or myeloid leukaemia (CGL) are clonal disorders of the pluripotent haemopoietic stem cells. We have studied granulocyte, megakaryocyte and erythroid progenitors from the peripheral blood of 7 patients with PP, 9 with ET, 19 with MF and 6 with CGL in order to characterise similarities and differences at the committed progenitor cell level. Spontaneous megakaryocytic and erythrocytic growth was characteristic of MF, PP and ET but was not seen in CGL. Circulating erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) progenitors were markedly increased in MF and CGL, less raised in ET and closest to normal in PP. Erythropoietin-independent erythroid bursts (EIBFU-E) grew from the blood of patients with MF, PP and ET but spontaneous growth of megakaryocytes occurred in only MF and ET. These results suggest a progression of increasing abnormality from PP, where EIBFU-E occurred with relatively normal numbers of circulating progenitors, to ET where both EIBFU-E and megakaryocyte precursors regularly occur with elevated numbers of progenitors, to MF where spontaneous BFU-E, CFU-Mk and CFU-GM occur at high levels.
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PMID:Primary polycythaemia, essential thrombocythaemia and myelofibrosis--three facets of a single disease process? 312 58

Erythropoietin concentrations were increased significantly (p less than 0.025) in nine cats with natural feline leukemia virus infection and associated erythroid aplasia compared to six clinically normal cats. Adult cats experimentally inoculated with the Kawakami-Theilen isolate of feline leukemia virus developed a progressive simultaneous increase in erythropoietin activity and decrease in packed cell volume. These findings indicate that erythroid aplasia associated with feline leukemia virus infection is not caused by a failure in erythropoietin production.
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PMID:Serum erythropoietin changes in cats with feline leukemia virus-induced erythroid aplasia. 631 29

The factor-dependent cell line, TF-1, established from a patient with erythroleukaemia, shows characteristics of immature erythroblasts. Addition of granulocyte-macrophage colony stimulating factor (GM-CSF) to the culture medium is required for long-term growth of the cells. Erythropoietin (Epo) can also be used to sustain TF-1 cells but for only limited periods (approximately a week). Low levels of both growth factors can act synergistically to maintain proliferation for a longer period of time than Epo alone. To eliminate the requirement of exogenous Epo for growth, TF-1 cells were co-cultured with a retroviral secreting cell line containing the human erythropoietin (hEpo) gene and a neomycin (neo) selectable marker. TF-1 cells which exhibited neo resistance (indicating infection by the retrovirus) were then grown in low concentrations of GM-CSF without the addition of Epo. Under these conditions growth of normal TF-1 cells was not sustained. The neo-resistant cells survived for more than 14 days indicating synergy between GM-CSF and the Epo synthesised by the co-cultured TF-1 cells. Radioimmunoassays performed on growth media detected concentrations up to 1 mU/ml of Epo, implying that stable integration of the retroviral vector and expression of the hEpo gene have been achieved.
Leukemia 1995 Oct
PMID:Retroviral-mediated gene transfer of the human erythropoietin gene into a factor-dependent cell line, TF-1. 747 17


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