Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new human leukemia cell line, designated as ME-1, was established from the peripheral blood leukemia cells of a patient with acute myelomonocytic leukemia with eosinophilia (M4E0). This cell line has the characteristic chromosome abnormality of M4E0, inv(16) (p13q22). When cultured in RPMI 1640 medium containing 10% fetal calf serum, ME-1 cells were monoblastoid, but with the addition of cytokines such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, or medium conditioned by phytohemagglutinin-stimulated human peripheral leukocytes (PHA-LCM), the cells exhibited differentiation to macrophage-like cells. PHA-LCM also promoted eosinophilic-lineage differentiation of this cell line, although IL-5 did not do so. To elucidate the mechanism of proliferation and differentiation of ME-1 cells, we studied the effect of a potent inhibitor of protein kinase C, 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7), on colony formation of ME-1 cells. H-7 inhibited colony formation of ME-1 cells by IL-3 or GM-CSF dose dependently, but had little inhibitory effect on colony formation by IL-4. These results indicate that the proliferation and differentiation of ME-1 cells by IL-3 or GM-CSF were related to the activation of protein kinase C, while those by IL-4 involved other regulatory systems. ME-1 cells should be useful for studying the pathogenesis of M4E0 and the mechanisms of proliferation and differentiation of leukemic and normal progenitors by cytokines.
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PMID:Establishment and characterization of a new human leukemia cell line derived from M4E0. 207 80

The effect of erythropoietin (Epo) on colony formation by blast progenitors in acute myeloblastic leukaemia other than erythroleukaemia was studied using a blast colony assay. Epo alone did not induce colony formation, but when it was used together with phytohaemagglutinin-stimulated leucocyte-conditioned medium (PHA-LCM) the number of leukaemic colonies significantly increased in nine out of 12 cases studies. Preincubation of Epo with anti-Epo antibody completely abolished this enhancement, indicating that the increase in colony numbers was caused by Epo itself. Cell surface phenotype analysis of colonies produced by Epo plus PHA-LCM showed no increase in percentages of erythroid and megakaryocyte lineages. The addition of Epo also increased the self-renewal capacity of leukaemic blast cells. Fresh leukaemic cells did not express Epo receptors, but they were induced after incubation with PHA-LCM. The present study thus showed that the proliferative response to Epo is not restricted only to the erythroid lineage, but also extends to AML blast cells other than those in erythroleukaemia in the presence of colony stimulating factors.
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PMID:Enhanced growth of clonogenic cells from acute myeloblastic leukaemia by erythropoietin. 237 25

The in vitro effect of recombinant human GM-CSF (rHuGM-CSF) was tested on bone marrow-derived multilineage (CFU-GEMM) as well as megakaryocytic (CFU-Mk), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitors in a group (n = 16) of patients with myelodysplastic syndromes (MDS). Hematopoietic progenitor cell growth was markedly impaired in MDS patients as compared to normal controls (p less than 0.05, at least). Recombinant HuGM-CSF supported the growth of CFU-GEMM, CFU-Mk, and BFU-E at lower, equivalent, or slightly higher frequencies that those found in cultures plated with medium conditioned by peripheral blood leukocytes (PHA-LCM), but it was invariably ineffective in improving growth values. Recombinant HuGM-CSF supported the growth of granulocyte-macrophage colonies in 15 of 16 cases. The overall incidence (mean +/- SEM) of CFU-GM in cultures containing rHuGM-CSF (5 ng/ml) was significantly higher than the one found in cultures stimulated with PHA-LCM (40 +/- 15 vs. 17 +/- 7, p less than 0.05). Upon culture with rHuGM-CSF (5 ng/ml), in 5 of 15 patients de novo colony formation was observed (8 +/- 4) and in 4 of 15 patients CFU-GM growth (129 +/- 33) fell within normal range. Doses of rHuGM-CSF higher than 5 ng/ml did not result in a further increase of MDS-derived colony formation. It is concluded that rHuGM-CSF (a) does not improve the growth of CFU-GEMM, CFU-Mk, and BFU-E; (b) may completely restore the growth of CFU-GM in a subgroup of MDS patients; (c) while ineffective in improving anemia and thrombocytopenia, its in vivo in MDS may correct leukopenia through an effect at the level of granulocyte-macrophage progenitor cell compartment, at least in a subset of highly responsive patients.
Leukemia 1989 May
PMID:Growth of human hematopoietic colonies from patients with myelodysplastic syndromes in response to recombinant human granulocyte-macrophage colony-stimulating factor. 265 96

In groups of 26 patients with myeloproliferative disorders (MPD), 8 with chronic myelogenous leukaemia (CML); 8 with polycythaemia vera (PV); 10 with essential thrombocythaemia (ET); and 6 patients with reactive thrombocytosis (RT), we studied the growth characteristics of bone marrow CFU-M in agar culture. The bone marrows from all the patients with MPD formed so called endogenous CFU-M colonies, in the absence of PHA-LCM, that increased in a dose-dependent manner with the addition of increasing concentrations of normal human AB-citrated plasma (NH-ABCP), while the bone marrows from all the patients with RT and from healthy controls formed few or no endogenous CFU-M colonies. In MPD, the endogenous CFU-M growth was enhanced by normal T cells in a dose-dependent fashion, and was decreased with the depletion of T cells from the marrow cells. These results suggest that the formation of endogenous CFU-M colonies is caused by hypersensitivity of CFU-M in MPD to NH-ABCP, which may contain a small amount of Meg-CSF, and/or by in vitro T cell stimulation. Among MPD, the endogenous CFU-M growth in ET was significantly lower than that of other MPD patients; however, the total number of ET CFU-M grown in the presence of PHA-LCM was the highest. These data show that the bone marrow CFU-M in MPD are heterogeneous with respect to in vitro growth pattern or sensitivity to exogenous Meg-CSF.
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PMID:Heterogeneity of in vitro growth pattern of megakaryocyte progenitors (CFU-M) in myeloproliferative disorders. 341 10

The effect of retinoic acid (RA) alone and in combination with cytosine arabinoside (Ara-C) on differentiation of fresh human myeloid leukaemic cells from patients with AML was studied. Cells from six patients: three with acute myelomonocytic leukaemia AMMoL and three with acute monoblastic leukaemia AMoL with a percentage of blasts greater than 70, were treated in an in vitro primary suspension culture with retinoic acid (10(-7) M), cytosine arabinoside (100 ng/ml) or both in combination. Non-adherent mononuclear cells were seeded at a concentration of 5 x 10(5) cells/ml in RPMI 1640 culture medium supplemented with 20 per cent fetal bovine serum and 10 per cent (PHA-LCM) phytohaemagglutinin leucocyte conditioned medium and incubated for 6 days at 37 degrees C in a humidified incubator containing 5 per cent CO2 in air. Morphological and functional differentiation into terminal mature elements was induced in all leukaemia cells of the six patients following exposure to the combination of both agents. These results suggest the potential usefulness of the combination of a differentiating agent (retinoic acid) and an antileukaemic drug (cytosine arabinoside) in the treatment of acute myeloid leukaemias: AMMoL and AMoL. This combination warrants a clinical trial.
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PMID:Retinoic acid alone and in combination with cytosine arabinoside induces differentiation of human myelomonocytic and monoblastic leukaemic cells. 342 32

The response of human myeloid leukemia cells to various sources of colony-stimulating activity (CSA) and media conditioned by phytohemagglutinin-stimulated mononuclear cells (PHA-LCM) was investigated in liquid and colony culture. PHA-LCM, placenta-conditioned medium, GCT cell line-conditioned medium, leukocyte-conditioned medium, and partially purified CSA for human and murine cells were tested for ability to support growth of granulocyte-macrophage colonies from adherent cell-depleted human bone marrow. This activity was correlated with ability to support leukemia colony growth in methylcellulose, and [3H]thymidine incorporation in liquid culture by normal bone marrow cells, leukemia cells, and the KG-1 myeloid leukemia cell line. For normal cells, growth and liquid culture responses were highly correlated for various sources of CSA (r = 0.92), and addition of data using PHA-LCM changed results only slightly (r = 0.89). [3H]thymidine incorporation by leukemia cells from patients without a prior history of a myeloproliferative disorder was also highly correlated with normal CSA (r = 0.97) for sources other than PHA-LCM. Responses of leukemia blasts and KG-1 cells in liquid culture to PHA-LCM appeared in excess of its CSA for normal cells. Colony growth by leukemia cells was not clearly correlated with either liquid culture activity for leukemia cells or CSA for normal cells. PHA-LCM was also not statistically superior to placenta-conditioned medium as stimulus for leukemia colony growth, but was superior to placenta-conditioned medium for some patients. Differentiation in culture did not appear to depend on CSA source. We conclude that normal myeloid cells respond to CSA in a highly correlated fashion in both colony and liquid cultures. The majority of myeloid leukemia cells respond to either PHA-LCM or CSA, but the ability of PHA-LCM to support leukemia cell growth is greater than its CSA content. The possibility exists that overlapping populations responsive to CSA and to PHA-LCM are present simultaneously in patients with myeloid leukemia.
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PMID:Response of human myeloid leukemia cells to various sources of colony-stimulating activity and phytohemagglutinin-conditioned medium. 660 Sep 65

Colony formation by granulocyte/macrophage and eosinophilic progenitor cells in the blood and/or bone marrow of four patients with "hypereosinophilic syndrome' (HES) was studied in agar culture. Colony-stimulating activity (CSA) was derived from leucocyte feeder layers (LFL) or from medium conditioned by phytohaemagglutinin-stimulated lymphocytes (LCM). The total numbers of colonies in the patients' blood and marrow were normal. When patients' marrow cells were cultured over LFL, the proportion of colonies that were eosinophilic was greater than normal (mean 21% vs 6%, P less 0.001) and this difference was accentuated when CSA was derived from LCM (mean 53% vs 15%, P less than 0.001). LCM derived from normal subjects and LCM prepared from HES patients had similar effects. In the blood the total number of colonies and the proportion of eosinophilic colonies were similar in patients and controls. The overall pattern of colony formation HES differed distinctly from that observed in a patient with eosinophilic leukaemia reported previously. We conclude that the proportion of eosinophil-committed progenitor cells in the marrow of patients with HES is increased, but we have failed to demonstrate a role for the patient's own lymphocytes in augmenting eosinophil production.
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PMID:Increased eosinophil colony formation in agar by haemopoietic cells from patients with the hypereosinophilic syndrome. 732 99