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

NFS-60 cells were previously obtained from leukemia cells that were infected with the Cas-Br-M murine leukemia virus in vivo. We examined the proliferation and differentiation capacity of NFS-60 cells in the presence of native and recombinant (r) interleukin 3 (IL-3), recombinant granulocyte colony-stimulating factor (rG-CSF), recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), and r-erythropoietin (Ep) using methylcellulose culture methods. This cell line was able to form colonies in response to each hemopoietic factor, but colony formation was rarely seen in their absence. Some populations of NFS-60 cells could differentiate into neutrophils and macrophages in the presence of IL-3 and GM-CSF. Moreover, in the presence of Ep, this cell line formed well-hemoglobinized colonies as well as nonerythroid colonies. In the presence of G-CSF, NFS-60 cells remained in the promyelocytic state. Electron microscopic studies confirmed these morphologies. A single-cell transfer experiment demonstrated that neutrophils, macrophages, and erythroblasts were derived from a single cell. It is concluded that the NFS-60 cell line is a factor-dependent, bipotential hemopoietic cell line.
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PMID:Bipotential murine hemopoietic cell line (NFS-60) that is responsive to IL-3, GM-CSF, G-CSF, and erythropoietin. 245 92

The blast cells of acute myeloblastic leukemia may be considered as a renewal population maintained by stem cells that are capable of both self-renewal and differentiation. Blast stem cells grow in culture usually when stimulated by growth factors normally active on myelopoietic cells. Two culture methods permit an evaluation of the balance between self-renewal and differentiation; previous studies have shown that this balance can be affected by recombinant growth factors. These include interleukin 3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF), active on early cells in normal myelopoiesis, and G-CSF and CSF-1, restricted in normal hemopoiesis to the granulopoietic and macrophage/monocytic lineages, respectively. In this paper we report the results of evaluating the effects on these recombinant growth factors alone or in mixtures of two at optimal concentrations. The results were obtained either using titrations of colony formation in methylcellulose or growth in suspension. Star diagrams, a technique from exploratory data analysis, were used to provide quantitative and graphic displays of the results of the recombinant factors on the balance between blast self-renewal and differentiation. Blasts from 4 acute myeloblastic leukemia patients and one patient with the blast crisis of chronic myeloblastic leukemia were examined in detail. The great patient-to-patient variation usually observed was seen in both plating efficiency in methylcellulose and growth pattern in suspension. In spite of this variation, a common pattern of response to growth factors emerged. When the early acting factors, IL-3 and GM-CSF, were combined, the effect was quantitatively and qualitatively similar to the largest stimulation seen with either of the factors alone. In contrast, late-acting factors, G-CSF and CSF-1, influenced each other's effects when present together and each affected the activities of GM-CSF and IL-3. Notably, CSF-1, which often led to the accumulation of adherent, terminal cells in suspension, usually maintained or increased this differentiation-like activity in combination. G-CSF also favored differentiation in combination, although the effect was usually to increase the number of colonies in methylcellulose, most of which consist of blast cells incapable of further divisions. The results are discussed as they relate to the postulated structure of the blast population and the normal targets of the recombinant growth factors.
Leukemia 1988 Jun
PMID:The effects of combinations of the recombinant growth factors GM-CSF, G-CSF, IL-3, and CSF-1 on leukemic blast cells in suspension culture. 245 60

We report here that extended culture of purified rat peritoneal mast cells (RpMC), typical of the connective tissue-type (CTMC), gives rise to continuously proliferative cell lines without the requirement of exogenous growth factors such as IL-3 and IL-4 or accessory cells. Two of the cell lines established, RCMC1 and RCMC2, are described here. Both cell lines have been maintained in continuous culture in vitro for over a year. Although these cell lines were derived from CTMC, they exhibit phenotypic characteristics of mucosal-type mast cells, i.e., they contain rat mast cell protease II (RMCP II), low levels of histamine and stain alcian blue+/safranin-. Previous studies have identified both high and low affinity receptors for IgE, designated Fc epsilon RI and Rc epsilon RII, respectively, on RpMC and rat basophilic leukemia (RBL) cells. At the early stages of cell culture, RCMC1 expressed predominantly Fc epsilon RI and a gradual increase in the expression of Fc epsilon RII has been observed with time in culture. By comparison, RCMC2 expressed predominantly Fc epsilon RII throughout its entire period of cell culture.
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PMID:Factor-independent tissue cultured mast cells: establishment from rat peritoneal mast cells. 245 19

The effects of combinations of recombinant human growth factors (colony-stimulating factor (CSF], interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony stimulating factor (G-CSF) for inducing proliferation of leukemic cells were compared in 27 acute myeloid leukemias (AMLs). While functional heterogeneity of AML was clearly shown, we further demonstrated that optimal growth may be obtained with combinations of CSF. The most striking feature was that, in both suspension and semisolid cultures, IL-3 and G-CSF acted synergistically in supporting AML cell proliferation except in cases for which G-CSF was found to be an inhibitory factor. In the majority of cases, the proliferative effects of the IL-3 and GM-CSF combination were significantly higher than the most potent of either factor present alone in the cultures. Finally, preincubation with IL-3 greatly potentiated the responsiveness of AML cells to subsequent addition of either GM-CSF or G-CSF. These results indicate that AML cells respond to growth factor in the same way as normal hemopoietic cells and that stimulation by a second late-acting growth factor such as G-CSF is also required to yield optimal growth.
Leukemia 1989 Mar
PMID:Recombinant human IL-3 and G-CSF act synergistically in stimulating the growth of acute myeloid leukemia cells. 246 64

Physiological inducers of myeloid cell growth and differentiation were used to simultaneously analyze the expression of the proto-oncogenes c-myc, c-myb, c-fos, c-fes and c-fms during normal myelopoiesis, where growth is coupled to differentiation, as compared with that in leukemia, where growth has been uncoupled from differentiation as well as upon suppression of the leukemic phenotype via induction of differentiation and growth arrest. Proto-oncogene expression was also used as a tool to dissect the growth to differentiation developmental cascade. Myeloid cell growth was correlated with high c-myc and c-myb RNA levels, decreasing to undetectable levels in terminally differentiated cells. No c-myc RNA was detected in normal myeloid progenitors induced for differentiation without growth, using media conditioned by mouse granulocytes (GCM), indicating that c-myc may play either no role or an inhibitory one in differentiation. RNA levels of the proto-oncogenes c-fos, c-fes and c-fms were undetectable in normal or M1 differentiation inducible (D+) leukemic myeloblasts, and were stably induced upon stimulation of the normal precursors for growth and differentiation, with highest levels at the time when most of the cells had undergone terminal differentiation. Only c-fes RNA was induced upon M1D+ differentiation. It was also shown to be induced upon induction of differentiation without growth in normal myeloid precursors. Using c-myc and c-myb RNA suppression as molecular markers for induction of M1D+ differentiation, the existence of myeloid differentiation factor(s), distinct from myeloid growth factors, has been demonstrated. Such differentiation inducing activity was found in media conditioned by mouse lungs or granulocytes, and was induced in normal myeloid precursors by the myelopoietic growth factors IL3, GM-CSF, G-CSF, and M-CSF. Taken together, the results of this study enhance and add to previous work to better correlate the expression of the proto-oncogenes myc, myb, fes, fos and fms with several parameters of normal and abnormal myeloid cell growth and differentiation. The results indicate that the normal myeloid growth to differentiation developmental cascade entails a mechanism whereby myeloid growth factors induce myeloid differentiation factors, subsequently suppressing c-myc and c-myb RNA expression, leading to the induction of differentiation and growth arrest, including early accumulation of c-fes RNA followed by accumulation of c-fos and c-fms RNAs. It was also indicated that this cascade is impaired in leukemia.
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PMID:Proto-oncogene expression and dissection of the myeloid growth to differentiation developmental cascade. 247 Nov 31

Various human lymphokines such as semipurified human interleukin 3 (IL 3), recombinant human IL 3, granulocyte colony stimulating factor (G-CSF), and recombinant human interleukin 4 (IL 4) stimulated growth of human bone marrow cells, but from all these factors tested, only IL 3 by itself was able to cause an increase in histamine content. Fibroblast monolayers as well as factors in their supernatants also increased proliferation and histamine content of bone marrow cells. Concentrated supernatants (Mr greater than 10,000) also inhibited cell proliferation and induced histamine content. The same fraction concentrated on a Mr cut-off greater than 50,000 enhanced cell growth and the total histamine content per culture. Thus, fibroblast supernatants contained both growth promoting and inhibitory factors. However, using the rat basophilic leukemia (RBL) cell line as a test system for such fibroblast-derived differentiation factors, we showed that if cell proliferation was inhibited, histamine content was also enhanced. Furthermore, certain drugs known to inhibit cell division, such as sodium butyrate or hydroxyurea, were also found to cause an increase in histamine content of RBL cells. Thus, our data demonstrate that basophil/mast cell differentiation, in terms of augmentation of cellular histamine levels, may be achieved by exposure to certain growth-inducing cytokines, factors inhibiting proliferation or pharmacological agents which inhibit cell proliferation.
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PMID:Factors influencing proliferation and histamine content of cultured human bone marrow cells. 247 28

We have tested a panel of recombinant hematopoietic growth factors (HGF) including the interleukins (IL) 1, 2, 3, 4, and 6 and the colony stimulating factors GM-CSF, G-CSF, M-CSF for their ability to induce proliferation of precursor B acute lymphoblastic leukemia cells (ALL) from 19 patients. In Ficoll-Isopaque isolated and T cell-depleted ALL bone marrow samples, IL2 (two cases), IL3 (four cases), and GM-CSF (one case) infrequently stimulated DNA synthesis measured by 3H-thymidine (TdR) uptake, and the other recombinant growth factors completely failed to do so. In repeat experiments with ALL blasts purified by fluorescence activated cell sorting (FACS), IL2, IL3, and GM-CSF responses could not be reproduced, suggesting that nonleukemic contaminant cells, and not the ALL blasts, had been stimulated by these factors. Cocktails containing combinations of IL1-IL4 and IL6 also lacked proliferation inducing potency. Depending on the purity of the incubated ALL cell samples, an impure preparation of B cell growth factors that has been reported to contain a highly effective stimulatory activity for precursor B ALL cells induced proliferation of residual normal cells as well as the ALL cells, as was evident from combined analysis of DNA synthesis and karyotyping. Exposure of the ALL blasts to artificial activators of protein kinase C and Ca2+ mobilization resulted in significant rises in 3H-TdR uptake, suggesting that these intracellular compounds are involved in transducing signals that upregulate proliferation. Although it remains possible that some of the human recombinant growth factors promote the growth of precursor B ALL cells in combination with other stimuli, a dominant role in the regulation of proliferation of these cells cannot be attributed to any of these cytokines at the present time.
Leukemia 1989 May
PMID:Recombinant hematopoietic growth factors fail to induce a proliferative response in precursor B acute lymphoblastic leukemia. 249 81

Regulatory effects on myelopoiesis and myelogenous leukaemia cell proliferation mediated by a human T cell clone (TCC) carrying a gamma/delta receptor have been studied. MHC-unrestricted cytotoxicity could be induced in this clone by culture with IL-2 but not IL-4. Increasing concentrations of IL-2 resulted in increased lysis of natural killer (NK)-susceptible target cells but lysis of NK-resistant targets could not be induced. Moreover, cytotoxicity on fresh chronic myeloid leukaemia cells was not measurable even after culture with 1000 U/ml IL-2. However, NK-resistant targets could be lysed when anti-receptor antibodies (OKT3 or TCR-delta 1) were added to the assay. Clone 290-2 cells secreted lymphokines potentially inhibitory for myelopoiesis (TNF-alpha, IFN-gamma), and their supernatants could inhibit optimally stimulated granulocyte/macrophage colony formation by normal bone marrow. Moreover, 290-2 cells prevented the consistently observed IL-3-stimulated enhancement of proliferation of CML cells, although even IL-3-pretreated leukaemic cells were still resistant to lysis by this clone. Thus, cells of this type, even when not directly cytolytic, could have a role in the regulation of myeloid cell growth.
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PMID:Regulation of normal myelopoiesis and chronic myelogenous leukaemia cell proliferation through a non-cytotoxic mechanism by a gamma/delta T cell clone. 253 Jan 64

The genetic structure and expression of the T cell receptor (TcR) loci were examined in pre-B and early hemopoietic cells. Thirty-eight percent of Abelson murine leukemia virus-transformed pre-B cell lines were rearranged at TcR gamma. Moreover, many pre-B cell lines were rearranged at two distinct gamma loci, V gamma 1.2 and V gamma 2. The gamma rearrangements in the pre-B cell lines were similar to those observed previously in T cell lines. V + C-containing gamma mRNA was detected in two pre-B cell lines. In all other pre-B and interleukin (IL) 3-dependent lymphoid and myeloid lines examined, smaller C gamma-containing mRNA were detected. These C gamma transcripts were independent of the genetic configuration of the gamma locus. In contrast, the TcR alpha and beta loci were in the germ-line configuration in all non-T cell lines examined and mRNA encoding these loci were not detected. When IL3-dependent lymphoid and myeloid cell lines were transformed to growth factor independence by a non-autocrine mechanism, no mRNA transcripts encoding TcR C gamma were detected. However, TcR C gamma mRNA transcripts were detected in factor-independent cell lines that arose by an autocrine mechanism. The cell cycle expression of C gamma was compared with protooncogenes and other marker genes previously shown to be cell cycle specific. mRNA transcripts encoding C gamma were detected in the highest amounts 4-8 h after IL 3, but not phorbol myristate acetate, addition. A similar time period of expression was observed with ornithine decarboxylase which has been shown to be expressed in G1 phase. These observations indicate that TcR gamma is often rearranged in pre-B cell lines and may be directly regulated by IL3 in IL3-dependent cells.
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PMID:Structure and expression of the T cell receptor gamma locus in pre-B and early hemopoietic cells. 255 23

We have examined the influence of recombinant, human IL-3 on normal and leukemic B cell precursors. CD10/CALLA+ leukemic B cell precursors, the pre-B cell line BLIN-1, and surface IgM-B cell precursors isolated from fetal bone marrow all responded to IL-3. This IL-3 response was dose-dependent and could be abrogated by a rabbit anti-IL-3 antiserum. Binding studies using radiolabeled IL-3 revealed the presence of approximately 200 high affinity IL-3 receptors on the BLIN-1 cell line, with a KD of 150pM. We conclude that normal and leukemic human B cell precursors express functional IL-3 receptors, extending the biologic range of this hematopoietin to the lymphoid lineage.
Leukemia 1989 Jun
PMID:Proliferative effect of interleukin-3 on normal and leukemic human B cell precursors. 265 29


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