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

The in vitro growth response of bone marrow and blood cells to granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) was studied in 18 acute myeloid leukemia (AML) patients using semisolid and suspension cultures. In 80% of the cases growth of leukemic progenitor cells was stimulated by GM-CSF and/or G-CSF, as judged by colony or cluster formation. In acute promyelocytic leukemia [t(15;17)], G-CSF stimulated and maintained the leukemic progenitors only transiently but fully stimulated the residual normal granulocyte/macrophage colony-forming units (CFU-GM). In some cases of M2 and M4 leukemia, G-CSF enhanced markedly the production of mature but cytochemically abnormal neutrophils. In some cases of M1 leukemia, neither CSF stimulated leukemic progenitors but instead stimulated only residual normal granulopoiesis. Spontaneous colony formation was observed in 20% of cases and was correlated with high-grade leukemic growth in vivo and a poor response to chemotherapy. The differing effects of the CSFs upon leukemic cells and residual normal granulopoiesis may have some implications for the clinical use of GM-CSF and G-CSF to overcome infectious complications.
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PMID:In vitro growth response to G-CSF and GM-CSF by bone marrow cells of patients with acute myeloid leukemia. 169 Aug 27

For granulocytic-macrophage progenitor populations and their progeny, five glycoproteins have been identified: GM-CSF, G-CSF, multi-CSF, M-CSF and IL-6 that can regulate their proliferative activity, maturation and functional activities. The same glycoproteins also have a capacity to induce irreversible differentiation commitment in normal bipotential granulocyte-macrophage progenitors and in some myeloid leukaemic cell lines, which suggests that common cellular processes exist in both situations. The leukaemia inhibitory factor (LIF) is a glycoprotein, with intriguing properties, which can either induce differentiation in some myeloid leukaemic cell lines or prevent differentiation in normal totipotential embryonic stem cells. The data from the LIF studies suggest a genetic mechanism controlling self-generation that is relatively simple and may be common to all cells. However, the actual cellular response observed appears to depend on the nature of the responding cell.
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PMID:The induction and inhibition of differentiation in normal and leukaemic cells. 169 Sep 2

Because human P40 T-cell growth factor, tentatively designated interleukin-9 (IL-9), was isolated through its ability to stimulate a human IL-3-dependent leukemic cell line (M-O7E), we tested the ability of IL-9 to support the growth and differentiation of normal hematopoietic progenitor cells from peripheral blood and bone marrow. Although the M-O7E cell line was derived from a patient with megakaryoblastic leukemia, IL-9 has not proved to be a growth or maturation factor for megakaryocytes, but instead has proved to be effective in supporting the development of erythroid bursts (BFU-E) in cultures supplemented with erythropoietin. Using highly purified progenitors from peripheral blood, IL-3 showed a BFU-E plating efficiency of 46% compared with 20% for IL-9. Because of the purity of these cell preparations and the low cell density in culture, IL-9 is likely to interact directly with erythroid progenitors. Analysis of mixing experiments and of the morphology of the BFU-E in culture indicated that IL-9 interacts preferentially with a relatively early population of IL-3-responsive BFU-E. In cultures of human bone marrow or cord blood, IL-9 selectively supported erythroid colony formation, while IL-3 and granulocyte/macrophage colony-stimulating factor additionally yielded granulocyte/macrophage colonies. Therefore, IL-9 represents a new T cell-derived cytokine with the potential for selectively stimulating erythroid development in the hematopoietic system.
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PMID:Human P40 T-cell growth factor (interleukin-9) supports erythroid colony formation. 169 25

In order to minimize the interactions of clonogenic cells with accessory cells and characterize the direct effect of recombinant hematopoietic growth factors (HGF) on acute myelogenous leukemia colony-forming cells (AML-CFU), the response of CD34+ AML-CFU to individual or combined recombinant HGF, i.e., interleukin-1 (IL-1), interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF), was studied in 10 patients and compared with the growth response obtained from unfractionated marrow cells. IL-3 and GM-CSF had a similar stimulating activity on AML-CFU growth. G-CSF resulted the most efficient stimulus for colony formation and was additive or synergistic with IL-3 and GM-CSF, M-CSF, used alone, had a negligible stimulating activity. When CD34+ cells were used, IL-1 by itself had a low stimulating activity and displayed little or no synergy with IL-3, GM-CSF, and G-CSF. On the contrary, when unfractionated cells were used, IL-1 was very effective in inducing AML-CFU formation and was markedly synergistic with IL-3 and GM-CSF. These results show that IL-1-induced leukemic colony formation is prevalently mediated by accessory cells. IL-6 supported AML-CFU growth in seven of 10 cases, thus showing a direct effect on CD34+ leukemic cells, and enhanced the growth of IL-3-(+47 to +167%) and GM-CSF-dependent (+60 to +110%) AML-CFU. Recloning studies of single colonies demonstrated that primary CD34+ AML-CFU, stimulated by IL-3 and GM-CSF, generated secondary and tertiary colonies, whereas primary AML-CFU stimulated by G-CSF and IL-6 failed to give rise to secondary colonies, thus indicating a complete suppression of self-renewal. Sequential recloning of colonies grown in the presence of IL-3 + IL-6 demonstrated that addition of IL-6 and IL-3-containing plates resulted in a nearly complete suppression of self-renewal. In conclusion, these results demonstrate the heterogeneity of the CD34+ leukemic cell fraction and indicate the existence of complex regulatory events at the level of CD34+ leukemic cells. Data obtained from recloning experiments are of therapeutic interest in view of the clinical application of HGFs in the treatment of myeloid leukemias.
Leukemia 1990 Aug
PMID:Growth of CD34+ acute myeloblastic leukemia colony-forming cells in response to recombinant hematopoietic growth factors. 169 11

Tumor necrosis factor (TNF) is a regulatory cytokine that has pleiotropic effects on hematopoietic cell growth and differentiation. The present studies have examined the effects of TNF on the differentiation of phorbol-ester resistant human KG-la leukemia cells. Treatment with 100 U/mL of TNF or 33 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) had no detectable effect on the growth of KG-1a cells. In contrast, TNF, but not TPA, induced cellular aggregation and expression of the ICAM-1 adhesion molecule in KG-1a cells. Furthermore, KG-1a cells responded to TNF, but not to TPA, with a partial down-regulation of c-myc mRNA levels and induction of M-CSF gene transcription. Previous work suggested that TNF induces M-CSF gene expression through activation of phospholipase A2 and eicosanoid production. The present studies also demonstrate that TNF stimulated phospholipase A2 activity. In contrast, there was no detectable increase in phospholipase A2 activity following TPA treatment. These results indicate that: 1) certain characteristics of the differentiated monocytic phenotype were induced by TNF in the phorbol ester-resistant KG-1a line, and 2) treatment with TNF and not TPA was associated with activation of phospholipase A2 during induction of monocytic differentiation in these cells.
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PMID:Induction of monocytic differentiation by tumor necrosis factor in phorbol ester-resistant KG-1a cells. 169 25

We have examined the in vitro effects of recombinant human (rh) interleukin-1 (IL-1) on the growth of purified megakaryoblasts obtained from patients with acute megakaryoblastic leukemia. We demonstrate that both IL-1 alpha and IL-1 beta treatment of these cells led to stimulation of DNA synthesis (as shown by increase of 3H-thymidine incorporation up to 35-fold) and also resulted in colony formation of leukemic megakaryoblasts. However, the stimulatory effect of IL-1 was dependent on endogenous production of IL-6, because addition of neutralizing monoclonal antibody (MoAb) to IL-6 abrogated the stimulatory activity of IL-1. In contrast, neutralizing MoAbs to granulocyte (G)-colony stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, and macrophage (M)-CSF failed to counteract the growth-enhancing effects of IL-1. Leukemic megakaryoblasts accumulated IL-6 mRNA and released IL-6 protein into their culture supernatant when exposed to rh IL-1 but failed to disclose transcripts for G-, GM-, and M-CSF under these conditions. Analysis of IL-6 receptor (IL-6R) transcript levels demonstrated that megakaryoblasts constitutively expressed IL-6R mRNA and that these transcripts are down-regulated to undetectable levels upon exposure to IL-1 and IL-6. Increase of 3H-thymidine incorporation by megakaryoblasts could be duplicated by exogenous IL-6 that could be blocked by neutralizing MoAb to IL-6. In conclusion, our results suggest that leukemic megakaryoblasts could produce and secrete IL-6, and express IL-6R, and that the growth-enhancing effect of IL-1 on these cells is indirect, via production of IL-6 by leukemic cells.
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PMID:Interleukin-6 (IL-6) is an intermediate in IL-1-induced proliferation of leukemic human megakaryoblasts. 170 Jul 30

The effects of recombinant human tumor necrosis factor alpha (TNF alpha) on colony growth were studied using highly enriched progenitor cells from normal human bone marrow. Supplementation of TNF to culture resulted in a dose-dependent suppression of granulocyte colony-stimulating factor (G-CSF) induced granulocytic colony formation and also erythropoietin (Epo) induced erythroid burst formation. However, the number of erythroid bursts, stimulated by interleukin-3 (IL-3) plus Epo, increased when TNF was added at comparable concentrations. Further, TNF enhanced eosinophilic colony growth induced by IL-3 or granulocytic-macrophage colony-stimulating factor (GM-CSF). In GM-CSF cultures TNF (100-1000 U/ml) also induced granulocytic and macrophage colonies. The addition of neutralizing antibodies against G-CSF, GM-CSF, or interleukin-6 (IL-6) to culture did not abrogate the observed effects of TNF, so that stimulation of myeloid colony growth was unlikely to result from the secondary induction of G-CSF or GM-CSF. TNF therefore exerts favourable effects on hematopoietic progenitors responsive to the more primitive colony-stimulating factors (IL-3, GM-CSF) and potent negative effects on precursors reactive to the single lineage G-CSF and Epo. These contrasting effects of TNF suggest that TNF, when available to marrow progenitors at similar tissue concentrations, may drive hematopoiesis within the progenitor cell compartment into selected directions.
Leukemia 1991 Jan
PMID:Positive and negative effects of tumor necrosis factor on colony growth from highly purified normal marrow progenitors. 170 38

Differentiation of a human eosinophilic leukemia cell line, EoL-1, induced by the culture supernatant of a human ATL cell line, HIL-3 (HIL-3 sup) was compared with differentiation induced by defined cytokines. HIL-3 sup induced EoL-1 cells to express eosinophilic granules and segmented nuclei after 6 to 9 days of incubation. HIL-3 sup also induced the expression of Fc epsilon receptor II (Fc epsilon RII/CD23) and an eosinophil differentiation antigen EO-1 mainly on eosinophilic granule (+) cells. Furthermore, HIL-3 sup induced EoL-1 cells to respond to an eosinophil chemotactic factor, platelet activating factor. HIL-3 cells express messenger RNA (mRNA) of interleukin-5 (IL-5), macrophage colony-stimulating factor (M-CSF), and IL-3 but not granulocyte CSF (G-CSF). Granulocyte-macrophage CSF (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha) were detected in the HIL-3 sup. Recombinant IL-2 (rIL-2), rIL-3, rIL-4, rIL-5, rM-CSF, and rGM-CSF did not induce eosinophilic granules. rG-CSF induced a few eosinophilic granule (+) cells, and TNF-alpha, which did not induce eosinophilic granules by itself, enhanced the ability of G-CSF to induce them. However, G-CSF and TNF-alpha did not induce the expression of Fc epsilon RII and EO-1 antigen. Moreover, anti-G-CSF, anti-TNF-alpha, anti-GM-CSF, anti-IL-3, and anti-IL-5 antibodies did not suppress the effect of HIL-3 sup on the differentiation of EoL-1 cells. All the data suggest that HIL-3 sup contains an unidentified factor that induces differentiation of EoL-1 cells, and that EoL-1 cells and HIL-3 sup provide an important model for the examination of differentiation mechanisms and functions of eosinophils.
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PMID:Differentiation of a human eosinophilic leukemia cell line (EoL-1) by a human T-cell leukemia cell line (HIL-3)-derived factor. 170 98

Granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) are increasingly used to stimulate granulopoiesis in neutropenic patients but in most cases without any knowledge of the endogenous CSF-levels. With the purpose to define serum levels of GM-CSF and G-CSF during induction chemotherapy and haematological reconstitution in patients with acute leukaemia we have used enzyme-linked immunosorbent assay (ELISA) techniques to measure these growth factors in 18 patients with acute myeloid leukaemia (AML) and eight patients with acute lymphoblastic or undifferentiated leukaemia (ALL/AUL). G-CSF above 0.05 ng/ml was detected in 54% of the analysed AML samples, median 0.29 (range 0.05-2.80) ng/ml; and in 40% of analysed ALL/AUL samples, median 0.09 (range 0.05-3.00) ng/ml. In patients with AML there was a clear correlation between an elevated serum concentration of G-CSF and documented infections. On the other hand, 15/18 of the patients with acute myeloid leukaemia and 8/8 patients with ALL/AUL had non-detectable levels of GM-CSF (less than 0.10 ng/ml). Two patients had measurable levels of GM-CSF in all samples, median 0.71 (range 0.26-1.18) ng/ml and in these patients the levels successively decreased during and after chemotherapy and did not increase in response to infections. In normals detectable levels of GM-CSF were found in 2/35 individuals and G-CSF in 0/10 individuals.
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PMID:Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in serum during induction treatment of acute leukaemia. 171 57

Among 52 patients diagnosed as acute myeloid leukemia (AML), nine cases were found in which interleukin-5 (IL-5) induced a proliferative response in the leukemic cells, as measured by the stimulation of DNA synthesis or colony formation in vitro. All cases (n = 7) with the cytogenetic abnormality t(8;21)(q22;q22) belonged to this group of IL-5 responders. Of the additional two cases, one had an apparently normal karyotype, but the other expressed a dicentric chromosome 21, an abnormality also involving the breakpoint region 21q22. The leukemic cells of the IL-5 responsive patients could also be stimulated to proliferate by IL-3, GM-CSF and G-CSF, and in some cases by IL-6 or M-CSF. Immunophenotypic analysis revealed the presence of the immature hematopoietic cell antigen CD34, the myelomonocytic maturation antigens CD13 and CD33, in association with the B-cell related surface marker CD19 on the leukemic cells. Immunoglobulin mu and T-cell receptor beta-genes in the leukemic cells were in germline configuration. Upon incubation in colony culture, clonogenic cells were capable of producing progeny showing eosinophilic or neutrophilic maturation following stimulation with IL-5 or G-CSF, respectively. It is concluded that IL-5 responsive AML represents a subgroup of leukemia with distinct immunotypic and cytogenetic features.
Leukemia 1991 Aug
PMID:Acute myeloid leukemias with chromosomal abnormalities involving the 21q22 region identified by their in vitro responsiveness to interleukin-5. 171 59


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