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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-adherent cord blood and bone marrow mononuclear cells were analyzed by multiparameter flow cytometry before and at day 2, 4, 7, and 11 of culture in recombinant interleukin 3 (IL-3) and granulocyte colony-stimulating factor (G-CSF, cord blood) or stem cell factor (SCF), IL3 and granulocyte-macrophage colony-stimulating factor (GM-CSF, BM) to assess the differentiation and maturational pathway of myeloid cells. Before cell culture cord blood contained progenitor cells (CD34+) in various differentiation stages (CD38(-)----CD38bright), mature lymphocytes, monocytes, and neutrophils, but no immature neutrophils and immature monocytes. During cell culture, all CD34+ cells acquired the CD38 antigen between day 2 and 5 of cell culture, the CD34 antigen was lost between day 5 and 11 of cell culture. Differentiation of cells into the myeloid cell lineage was characterized by the acquisition of both CD33 and CD71. The latter is indicative for the active proliferation of these cells. Maturation of the cells into the neutrophilic pathway was indicated by the acquisition of first the CD15 antigen followed by CD11b and CD16 respectively. Whereas maturation of the cells into the monocytic pathway was indicated by the acquisition of first CD11b followed by CD14 and a dim expression of both CD15 and CD16. In normal bone marrow, cells of various maturational stages are already present before cell culture. During cell culture differentiation of cells into the myeloid lineage and maturation of the cells along the monocyte and neutrophilic lineage followed identical pathways as was observed before cell culture. Differentiation and maturational pathways of cord blood and adult bone marrow were identical. The results confirm the surface-antigen-defined pathways of myeloid cell differentiation described previously for non-cultured normal bone marrow aspirates. The detailed assessment of cell maturation and differentiation of cultured cells by multidimensional flow cytometry permits the determination of the specific effects of various recombinant human growth factors on myeloid cells.
Leukemia 1992 Oct
PMID:Differentiation and maturation of growth factor expanded human hematopoietic progenitors assessed by multidimensional flow cytometry. 140 53

Myeloid leukemia development requires the acquisition by a cell of two abnormalities: an abnormal capacity for self-replication; and a capacity for autocrine stimulation, usually involving the known growth factors for granulocyte-macrophage cells. Curiously, in human leukemia, this does not usually result in autonomous growth when assessed in clonal in vitro cultures. Depending on gene programming, in particular in human or murine myeloid leukemias, the hemopoietic growth factors can also suppress the leukemic population by inhibiting the capacity of the leukemic stem cells for self-generation. The regulator showing the highest suppressive activity varies from leukemia to leukemia, with G-CSF. GM-CSF, IL-6, or leukemia-inhibitory factor (LIF) all having high activity on appropriate target cells. Combinations of these regulators are more effective than single agents alone. Analyses of human HL60, U937 and murine M1 leukemic models indicate that the development of morphological maturation in the leukemic cells is not a necessary feature of stem-cell suppression. LIF has an anomalous action on stem-cell self-generation, being highly effective in the suppression of certain myeloid leukemic cell lines, but being necessary to maintain self-generation in normal embryonic cells. This suggests the existence of a common control medium governing self-generation decisions in cells of different lineages, but that the outcome of the decision is determined by the differentiation program operating in different cells. The colony-stimulating factors are being used in combination with chemotherapy in the treatment of patients with acute myeloid leukemia, but the above principles require caution in certain situations.
Leukemia 1992
PMID:Role of hemopoietic growth factors in the development and suppression of myeloid leukemia. 160 21

Thuja polysaccharide g fraction (TPSg) was shown to be an inducer of the CD4+ fraction of the human peripheral blood T-cell subset (1,2). Furthermore, it could be demonstrated that TPSg is a potent inhibitor of the expression of HIV-1-specific antigens and of the HIV-1-specific reverse transcriptase (3). This report deals with the cytokine pattern induced by TPSg in human peripheral blood lymphocyte (PBL) and purified monocyte/macrophage cultures. In addition, a further characterization of the CD4+ T-cell fraction stimulated by TPSg was performed by FACS analysis. TPSg is induces IL-1 beta, IL-2, IL-3, IL-6, gamma-IFN, G-CSF, GM-CSF, and TNF-beta production in PBL cultures; and IL-1 beta and IL-6 in monocyte/macrophage cultures. Enzyme-linked immunosorbent assays (ELISAs) demonstrated that no IL-4 was produced by PBL cultures under TPSg influence.
Leukemia 1992
PMID:Mitogenic activity of high molecular polysaccharide fractions isolated from the cuppressaceae Thuja occidentalis L. enhanced cytokine-production by thyapolysaccharide, g-fraction (TPSg). 160 22

In this study we demonstrate that tumor necrosis factors (TNF alpha and TNF beta) are potent modulators of the in vitro proliferation of human AML cells. Blast cells from 11 cases of acute myeloblastic leukemia (AML) were incubated with recombinant TNF alpha or TNF beta in serum-free 3H-TdR uptake and colony culture systems in the presence or absence of recombinant interleukin-3 (IL-3), granulocyte macrophage colony-stimulating factor (GM-CSF), G-CSF, or M-CSF. Depending on the supplemented CSF, TNF could upregulate or suppress AML blast proliferation. Enhancement of AML growth by TNF was observed in the presence of IL-3 (in 9 of 11 cases in 3H-TdR assay; 6 of 9 cases in colony assay) and GM-CSF (in 8 of 11 cases in 3H-TdR assay; 4 of 9 cases in colony assay). In certain cases in which IL-3 or GM-CSF alone was unable to induce proliferative responses of AML cells, the simultaneous addition of TNF elicited colony growth and DNA synthesis suggesting a synergistic action between TNF and IL-3 or GM-CSF. In contrast, TNF suppressed G-CSF-induced growth (9 of 10 cases in 3H-TdR assay; 5 of 6 cases in colony assay). TNF could also stimulate DNA synthesis (in 2 of 11 cases) or colony formation (in 2 of 9 cases) in AML cultures without the addition of other growth factors. Experiments with neutralizing antibodies and specific radioimmunoassays for individual CSFs showed that the synergistic and antagonistic effects of TNF on AML growth could not be attributed to a release of one of these CSFs by the AML cells. The opposing consequence of exposure of AML blasts to TNF are of interest in view of our understanding of the pathophysiology of AML growth and the in vivo application of recombinant cytokines in AML patients.
Leukemia 1990 Jan
PMID:Modulation of colony stimulating factor-(CSF) dependent growth of acute myeloid leukemia by tumor necrosis factor. 168 38

Using a human G-CSF cDNA as a probe, we analyzed the t(15;17) breakpoint by Southern blot analysis with conventional and/or pulsed-field gel electrophoresis in 12 patients with acute promyelocytic leukemia. The results did not show the rearrangement, deletion, or restriction fragment length polymorphism within the gene and in the surrounding sequences.
Leukemia 1990 Jul
PMID:Lack of involvement of the G-CSF gene by chromosomal translocation t(15;17) in acute promyelocytic leukemia. 169 4

Monoclonal antibody YB5.B8 was previously shown to inhibit haemopoietic colony formation in response to a complex growth factor supplement in vitro (Cambareri A. C., Ashman L. K., Cole S. R. & Lyons A. B. (1988), Leukemia Res. 12, 929). We now report studies of the effect of the antibody on colony formation by normal human bone marrow cells in response to recombinant human colony-stimulating factors GM-CSF, G-CSF and IL-3. MAb YB5.B8 significantly reduced the yield of colonies of all types examined (granulocyte-macrophage, granulocyte, macrophage and eosinophil) in response to GM-CSF but not to IL-3 or G-CSF. However, MAb YB5.B8 failed to influence the proliferation of the myelomonocytic leukaemia cell line RC-2A in response to GM-CSF, G-CSF or IL-3. Direct binding studies demonstrated the presence of low numbers of receptors for GM-CSF on RC-2A cells, however, the binding of this cytokine was not influenced by co- and/or pre-incubation with MAb YB5.B8. Therefore the antigen identified by YB5.B8 is probably not a receptor for GM-CSF and may indirectly influence the response of normal haemopoietic progenitors to this cytokine.
 ...
PMID:A monoclonal antibody that inhibits the action of GM-CSF on normal but not leukaemic progenitors. 169 6

We established the continuous growth of WEHI-3B D+ cells in protein-free chemically defined F-12 medium by stepwise decreases in the concentration of fetal calf serum. This cell line, designated as WEHI-3B-Y1, has now been propagated in protein-free F-12 medium for 3 years. The population-doubling time of the cells in culture is about 24 hr. WEHI-3B-Y1 cells are immature undifferentiated cells which show positive staining for naphthol ASD chloroacetate esterase and alpha-naphthyl butyrate esterase and spontaneously exhibit a low level of differentiation to mature granulocytes and macrophages. Medium conditioned by WEHI-3B-Y1 cells stimulated the proliferation of an interleukin-3 (IL-3)-dependent FDCP-2 cell line. This conditioned medium was shown to have erythroid burst-promoting activity when assayed using normal murine bone marrow. The colony formation of WEHI-3B-Y1 cells in semi-solid agar culture was not stimulated by purified recombinant human granulocyte colony-stimulating factor (rhG-CSF). However, in the presence of human transferrin, rhG-CSF enhanced the number of colonies of WEHI-3B-Y1 cells but did not induce their differentiation. These results suggest that WEHI-3B-Y1 cells cultured in protein-free medium produced murine IL-3. In addition, human G-CSF enhanced the clonal growth but did not induce the differentiation of WEHI-3B-Y1 cells cultured in serum-free medium.
Leukemia 1990 Oct
PMID:Growth and differentiation of a murine interleukin-3-producing myelomonocytic leukemia cell line in a protein-free chemically defined medium. 169 90

The c-kit proto-oncogene encodes a transmembrane receptor with a tyrosine kinase internal domain. C-kit has been mapped to the W locus in the mouse, and the gene encoding the ligand has been shown to be the product of the murine SI locus. Previous genetic studies have shown that the murine W and SI loci play important roles in the normal function of hemopoietic stem cells. As these stem cells have been identified as the origins of abnormal clones in acute myeloblastic leukemia (AML), a study was begun of c-kit in AML. By Northern blot analysis, it was shown that all of 21 blast populations from AML patients were kit expression positive, but some AML cell lines did not transcribe detectable c-kit mRNA. This study is now extended to the responses of freshly obtained AML cells and cell lines to the ligand, mast-cell growth factor (MGF). In culture, fresh cells usually responded to added ligand with increases in both self-renewal and terminal divisions. The most obvious effects were seen when MGF was combined with either IL-3 or G-CSF. The response of cell lines to MGF mirrored their expression of c-kit; expression positive lines responded in culture with patterns similar to those seen for fresh cells. C-kit expression negative cells did not respond to MGF. RNA prepared from the cells giving rise to one such line, OCI/AML-5, was available for study. mRNA for c-kit could not be detected in this RNA sample by Northern blot analysis or the polymerase chain reaction. Thus the heterogeneity found in AML blast populations extends to the involvement of c-kit and its ligand in growth regulation, although blast populations without this regulatory apparatus appear to be rare.
Leukemia 1991 Jun
PMID:Mast cell growth factor, a ligand for the receptor encoded by c-kit, affects the growth in culture of the blast cells of acute myeloblastic leukemia. 171 40

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

This paper describes the properties of a continuous cell line derived from the blast cells of a patient with acute myeloblastic leukemia (AML), secondary to the treatment of Hodgkin's disease. The line grows slowly without stimulation but responds to interleukin-3 (IL-3), GM-CSF and mast cell growth factor (MGF), a ligand for the receptor encoded by the c-kit oncogene. When OCI/AML-4 cells are exposed to MGF with IL-3 or GM-CSF, additive or synergistic effects are seen. Combinations of MGF and G-CSF, IL-6 or CSF-1 give less growth than MGF alone. OCI/AML-4 cells are sensitive to retinoic acid; a dose related decrease in clonogenic cells is observed when OCI/AML-4 cells are exposed to retinoic acid in suspension culture. OCI/AML-4 cells are sensitive to cytosine arabinoside (ara-C), but the ara-C dose-response curve can be changed by altering the regulatory milieu in suspension culture. The cells are more ara-C sensitive in MGF or G-CSF than in IL-3 or GM-CSF. Following a 24 h exposure to retinoic acid, the ara-C sensitivity increases; in contrast, after a similar exposure to hydrocortisone, the cells become less ara-C sensitive. These changes in ara-C sensitivity occur in cells that are actively making DNA, as indicated by the reduction in colony formation after exposure to tritiated thymidine. Since OCI/AML-4 cells respond to many of the regulators that affect the growth of freshly obtained AML blast cells, it is proposed that this cell line may be useful for the study of regulation on AML in general and the interaction between different regulators in particular.
Leukemia 1991 Aug
PMID:OCI/AML-4 an acute myeloblastic leukemia cell line: regulation and response to cytosine arabinoside. 171 61


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