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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 action of recombinant human leukemia inhibitory factor (LIF) and 1-beta-D arabinofuranosylcytosine (ara-C) was studied on the human leukemia cell line U 937. Parameters investigated included monitoring of transcript levels of the proto-oncogenes C-MYC, C-FOS, and C-FMS, and analysis of nitroblue tetrazolium (NBT) reduction and of surface expression of the C3 bi receptor. Furthermore clonal proliferation of U 937 cells was assessed in soft agar cultures. The results indicate that both agents have only little effects on U 937 cells when acting alone. When combined in culture, however, they synergize to induce monocytic differentiation of U 937 cells as disclosed by significant increase of cells capable of reducing NBT and displaying surface C3 bi receptor that was accompanied by reduction of clonogenicity in colony assays. Induction of differentiation and inhibition of proliferation of U 937 cells was preceded by downregulation of transcript levels of C-MYC, increase of C-FOS mRNA, and induction of accumulation of C-FMS mRNA. By sequential use of LIF and ara-C we also demonstrate that the basis of synergism of both agents does not involve mechanisms at the level of receptor ligation but that synergism may be initiated by complementary intracellular metabolic cascades.
Leukemia 1990 Sep
PMID:Synergistic effect of recombinant human leukemia inhibitory factor (LIF) and 1-beta-D-arabinofuranosylcytosine (Ara-C) on proto-oncogene expression and induction of differentiation in human U 937 cells. 214 31

Vanadate, at concentrations between 0.5 and 2 mM, rapidly decreased the basal level of P-enolpyruvate carboxykinase (GTP) (EC 4.1.1.32) mRNA and blocked the dibutyryl cyclic AMP (Bt2cAMP)-induced increase in enzyme mRNA in both FTO-2B and H4IIE rat hepatoma cells. The concentration of vanadate necessary to inhibit the expression of this gene was similar to that required for the vanadate-mediated activation of the insulin receptor tyrosine kinase. To determine whether vanadate could inhibit PEPCK gene transcription, a series of chimeric genes containing several deletions in the P-enolypyruvate carboxykinase promoter between -550 and -68 was linked to the structural genes for either amino-3-glycosyl phosphotransferase (neo) or chloramphenicol acetyltransferase and introduced into hepatoma cells using three methods: (a) infection with a Moloney murine leukemia virus-based retrovirus, (b) transfection and stable selection for neo expression, or (c) transient expression of chloroamphenicol acetyltransferase. In FTO-2B hepatoma cells infected with retrovirus, vanadate rapidly (within 1 h) inhibited transcription of the PEPCK-neo gene and blocked induction of gene expression caused by the addition of either Bt2cAMP or dexamethasone to the cells. Vanadate was not a general transcription inhibitor since, it like insulin, stimulated the expression of the c-fos gene. Also, the inhibitory effect of vanadate was rapidly reversible in FTO-2B cells since PEPCK gene expression could be stimulated by Bt2cAMP and dexamethasone after removal of vanadate. A series of 5' deletions in the P-enolpyruvate carboxykinase promoter (-550 to +73) was ligated to the structural gene for neo and stably transfected into hepatoma cells. Sequences responsive to vanadate were detected between -109 and -68. This result was confirmed using H4IIE hepatoma cells transiently expressing the PEPCK-CAT gene. The most likely target for vanadate in that region of the P-enolpyruvate carboxykinase promoter is cAMP regulatory element 1 which maps from -91 to -84. A comparison of the inhibitory effects of insulin and vanadate in this system indicated a major difference in the site of action of these two compounds on PEPCK gene transcription.
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PMID:Vanadate inhibits expression of the gene for phosphoenolpyruvate carboxykinase (GTP) in rat hepatoma cells. 216 40

Induction of differentiation to macrophages in two different clones of myeloid leukemic cells by the hematopoietic regulatory proteins interleukin-6 (IL-6), or by granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), is shown to be associated with sustained accumulation of c-jun, jun-B, and c-fos mRNA that code for proteins that form complexes that are transcription factors (AP-1). In one but not in the other of these leukemic clones, differentiation is also associated with sustained accumulation of mRNA for the putative transcription factor zif/268. The results indicate that differentiation of myeloid cells by normal hematopoietic regulatory proteins is associated with induction of sustained elevated levels of mRNA for transcription factors that can regulate and maintain gene expression in the differentiation program, and that zif/268 gene expression is not essential for differentiation to macrophages.
Leukemia 1990 Dec
PMID:Induction of genes for transcription factors by normal hematopoietic regulatory proteins in the differentiation of myeloid leukemic cells. 224 2

High-affinity receptors for interleukin 2 (IL-2) are expressed on T cells following activation. These receptors are composed of both alpha and beta chains. Expression of alpha chains and, therefore, expression of high-affinity receptors are critically regulated at the level of transcription initiation. We have further dissected the regulatory elements involved in controlling transcription of the IL-2 receptor alpha-chain (IL-2R alpha) gene. The IL-2R alpha promoter contains a kappa B site and binding sites for additional nuclear factors within a 50-base-pair region (positions -290 to -240 relative to the major transcription start site). These include one upstream of the kappa B site and one similar to the c-fos serum response element (SRE), which is downstream of the kappa B site. Mutation of the kappa B site decreases IL-2R alpha promoter activity in MT-2 cells (a T-cell line that has been transformed with human T-cell lymphotropic virus type I), but not in Jurkat cells (a T-cell leukemia line) that have been activated by phorbol 12-myristate 13-acetate (PMA). In contrast, mutation of a region upstream of the kappa B site decreases activity in PMA-induced Jurkat cells but increases activity in MT-2 cells. Mutation of the SRE-like site decreases activity in both cell types but the effect in PMA-induced Jurkat is more pronounced. Thus, these distinct cis-acting elements play different physiological roles in IL-2R alpha gene activation in MT-2 cells and PMA-induced Jurkat T cells. These studies provide direct evidence for a functionally significant SRE-like sequence in a gene other than c-fos and the actin genes and identify other elements that are critical for IL-2R alpha gene expression.
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PMID:The same target sequences are differentially important for activation of the interleukin 2 receptor alpha-chain gene in two distinct T-cell lines. 230 42

Phorbol ester-induced differentiation of human B-chronic lymphocytic leukaemic cells was found to be preceded by a rapid transient induction in expression of the c-jun proto-oncogene, which paralleled that of c-fos. Induced expression of c-myc but not of c-fos/c-jun proto-oncogenes was markedly higher in a proliferating variant leukaemic cell population compared with that seen in typical lymphocytic leukaemia cells. These data suggest that the c-fos/c-jun nuclear oncogenes play a role in induced differentiation, whilst c-myc is more important in the proliferative response of B lymphocytes.
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PMID:Patterns of nuclear proto-oncogene expression during induced differentiation and proliferation of human B chronic lymphocytic leukaemia cells. 231 71

The intracellular Na+/K+ ratio was studied for its effect on expression gene beta-actin and oncogene c-fos and activity of these genes during the mitotic cycle in ascites cells of leukemia P-388 and Ehrlich tumour. It was established that gene beta-actin was activated at high and low ratios of Na+/K+, while c-fos only at high ones. The expression of these genes during the mitotic cell cycle was due to changes in the intracellular Na+/K+ ratio. The obtained data showed an important role of intracellular homeostasis of monovalent cations in regulation of gene expression during the mitotic cell cycle.
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PMID:[Effects of intracellular Na+/K+ ratio on expression of c-fos oncogene and beta-actin gene in ascitic cells of leukemia P-388 and Ehrlich tumor]. 237 85

The McDonough strain of the feline sarcoma virus contains a transforming gene (v-fms) which contains partial nucleotide homology with proto-oncogenes encoding tyrosine kinases. One of the v-fms-encoded products, gp140fms, is a cell surface transmembrane glycoprotein that may function as a growth factor receptor. Although c-fms transcripts have been detected in placental trophoblasts and normal human bone marrow, the role of the c-fms gene product is unknown. We now report that induction of monocytic, but not granulocytic, differentiation of human HL-60 leukaemic cells is associated with expression of c-fms, preceded by that of c-myc and c-fos. Because c-fms transcripts are also detectable in peripheral blood monocytes and in blasts from certain patients with myelomonocytic leukaemia, the c-fms gene product may play a role in monocytic differentiation.
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PMID:Expression of the c-fms proto-oncogene during human monocytic differentiation. 240 50

Transcription of the c-fos gene is transiently activated to generate large amounts of unstable c-fos RNA when quiescent fibroblasts are stimulated by polypeptide mitogens or whole serum. A cloned human c-fos gene (c-fosH) transfected into mouse fibroblasts is regulated in a similar manner. An element essential for transcription activation is located between nucleotides -332 and -276 relative to the mRNA cap site. This element has properties similar to those of previously characterized transcription enhancer elements. However, replacement of the 5' activating element by enhancers from SV40 or Moloney murine leukemia virus does not allow regulated c-fosH expression. The study of fusion genes showed that in addition to the 5' activating element, transient accumulation of c-fosH RNA following serum stimulation requires sequences at the 3' end of the c-fosH gene.
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PMID:Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5' element and c-fos 3' sequences. 241 12

RNA transcript levels of the protooncogenes c-myc, c-fos, and c-fms were measured in bone marrow cells obtained from patients with acute myelocytic leukemia at diagnosis or in complete remission. As controls, normal bone marrow cells were studied. The c-myc RNA levels are significantly higher in acute myelocytic leukemia cells at diagnosis than in remission or in normal marrow cells. In most instances the high c-myc RNA levels are a reflection of the high proportion of immature cells present in leukemic marrows. The bone marrow cells of several patients contain extremely high levels of c-myc RNA, levels which cannot be accounted for by the proportion of immature cells present in the bone marrow. The leukemic cells of patients with morphologically indistinguishable leukemias manifest different patterns of c-myc, c-fos, and c-fms expression. This observation is consistent with differences in behavior of leukemic cells even among patients with the same French-American-British type of leukemia. The normal-appearing bone marrow cells of some acute myelocytic leukemia patients in complete remission differ from normal bone marrow cells in having slightly higher c-myc RNA levels, as well as in the pattern of expression of c-fos and c-fms. The possible use of protooncogene expression patterns to subdivide the French-American-British categories of acute myelocytic leukemia into subtypes with greater prognostic significance is discussed.
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PMID:Expression of the protooncogenes c-myc, c-fos, and c-fms in acute myelocytic leukemia at diagnosis and in remission. 243 29

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


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