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)

Five clonal cell lines were established from a spontaneous BALB/c mouse osteosarcoma, and characterized. Four of these lines showed some similarities in morphology, in vitro growth properties, production of collagenous and noncollagenous extracellular matrix proteins and osteogenic differentiation. The cells formed colonies with characteristic differences in size and morphology in soft agar, and osteogenic sarcomas and metastases in syngeneic mice after transplantation. Ultrastructurally, cells in the transplant tumours showed marked osteogenic features. There were no osteoclast-like cells. The fifth cell line had somewhat different characteristics. All five lines expressed infectious endogenous murine leukemia viruses. Increased c-myc protoon-cogene expression was found in one cell line and c-fos expression at different levels in all lines. There was only very low expression of c-Ha-ras and no expression of c-Ki-ras and c-sis. DNA analysis showed the presence of newly acquired proviral genomes integrated at different sites in the cellular DNA. The results show that distinct osteogenic neoplastic subclones can be obtained from a primary mouse osteosarcoma. Although the clones exhibited an appreciable morphological, functional, and molecular diversity they retained the basic pathogenic properties of the tumour from which they were derived.
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PMID:Establishment and characterization of osteogenic cell lines from a spontaneous murine osteosarcoma. 324 85

Expression of both the c-fos and c-sis protooncogenes during myeloid differentiation has been detected in cells of the monocytic lineage. Since an increase in c-fos transcripts was not detected during dimethylsulfoxide induced HL-60 granulocytic differentiation, it was suggested that within the myeloid series c-fos gene expression might be lineage specific. In the present study, we have determined whether expression of the c-fos and c-sis genes is indeed specific for the monocytic pathway or rather common to both the granulocyte and monocyte pathways. C-fos and c-sis gene expression was analyzed in freshly isolated human granulocytes and monocytes, in human HL-60 promyelocytic leukemia cells induced to differentiate along the granulocytic or monocytic pathway, in myeloblasts from five patients with the M1 or M2 subtype of acute myeloblastic leukemia (AML) and in blasts from six patients with M4 myelomonocytic leukemia. The level of c-fos mRNA was fifteen times higher in granulocytes as compared with monocytes. An increase in c-fos expression was also found in HL-60 cells differentiated along the granulocytic pathway after exposure to hypoxanthine, hexamethylene bisacetamide, and the combination of retinoic acid and dibutyryl adenosine 3'5' cyclic monophosphate. Three of 5 M1 and M2 leukemic myeloblast preparations depleted of lymphoid and monocytic cells and all six M4 leukemic cells expressed c-fos transcripts. In contrast, c-sis gene transcripts were detectable in monocytes and during drug induced monocytic differentiation of the HL-60 cells but not in granulocytes during granulocytic differentiation of the HL-60 cells or in AML samples. Thus, in the myeloid series, c-sis gene expression is lineage specific while expression of the c-fos gene is found in both lineages and may be related to metabolic pathways common to both granulocytes and monocytes.
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PMID:c-sis but not c-fos gene expression is lineage specific in human myeloid cells. 327 63

The exposure of a polyoma virus transformed rat fibroblast cell line H3 to UV-C irradiation (254 nm) causes a transient increase in the abundance of RNAs for the cellular oncogenes c-H-ras, c-myc and c-fos, as well as RNAs homologous to an endogenous rat leukemia virus-related sequence (RaLV). Treatment with cycloheximide also causes a transient increase in the c-H-ras, c-myc and RaLV RNAs, with a time course similar to that obtained with UV irradiation. UV-C irradiation also causes a transient increase in the RNAs for c-H-ras and c-myc in an SV40 transformed human keratinocyte cell line SVK-14. Dose response studies with UV light at the various wavelengths found in sunlight indicate that UV-B (270-330 nm) and UV-A (345-440 nm) are much less potent than UV-C in inducing increased levels of c-H-ras and c-myc RNAs in SVK-14 cells. Thus, in addition to the well known mutagenic effects of UV irradiation, UV damage to DNA can also lead to increased expression of cellular oncogenes in both rodent fibroblasts and human keratinocytes.
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PMID:Ultraviolet light induces the expression of oncogenes in rat fibroblast and human keratinocyte cells. 328 98

The relationship between the expression of the c-fos proto-oncogene and the expression of the class I major histocompatibility (MHC) antigens during the early stages of induced differentiation in three different leukemic cell lines was examined. In the U937 histiocytic lymphoma line TPA induced an increase in mRNA and cell surface MHC expression which followed induction of c-fos. In contrast, in the murine erythro-leukemia cell line, DMSO induced declining constitutive c-fos levels that were accompanied by declining mRNA and cell surface MHC expression. In the pluripotent HL60 promyelocytic line induction of macrophage differentiation with TPA led to c-fos induction and rising MHC levels, whereas induction of granulocyte differentiation with DMSO did not induce c-fos expression and was followed by declining MHC levels. Taken together, the results suggest that the c-fos proto-oncogene might be involved in the control of class I MHC antigen expression during differentiation.
Leukemia 1987 Mar
PMID:Expression of major histocompatibility class I genes in differentiating leukemic cells is temporally related to activation of c-fos proto-oncogene. 331 38

DNA-specific agents have the capacity to induce the maturation of ML-1 human myeloblastic leukemia cells to monocyte/macrophages if adequate concentrations of fetal bovine serum or mitogen-stimulated human leukocyte-conditioned medium (CM) are present in the culture medium. Fetal bovine serum and CM contain specific differentiation-inducing factors that, in conjunction with the drugs, bring about cell maturation. To examine the mechanism by which this interactive effect occurs, ML-1 cells were exposed to actinomycin D or daunomycin in various combinations with CM, using concentrations at which neither the drug nor CM, when applied individually, induced maturation to a significant extent. Pretreatment for 3 days with drug followed by treatment for 3 days with CM caused maturation of 75% of the cells, as determined by the appearance of Fc receptors. Other markers of differentiation, including alpha-napthyl acetate esterase, acid phosphatase, and morphology, also reflected the increase in maturation. The simultaneous application of drug and CM was equally effective in inducing differentiation. Pretreatment of the cells with CM followed by treatment with drug failed to induce maturation, whereas pretreatment with CM followed by a second application of CM caused the expression of Fc receptors in 62% of the cells. In contrast, pretreatment with drug followed by a second application of drug did not induce differentiation significantly. These results indicate that the drug sensitizes the cells to respond to concentrations of CM to which they would otherwise be refractive. The drug-induced sensitization is reversible. At sensitizing drug concentrations, cell viability was preserved but, as measured by radiolabeling for 1 h, total RNA synthesis was decreased by 38% and mRNA synthesis by 87%. At these drug concentrations, the synthesis of mRNA specified by all seven oncogenes examined (myb, myc, abl, fos, N-ras, sis, erb B) was decreased by 15-60%. The administration of CM subsequent to drug caused a further decrease of some mRNA levels (c-myb, c-myc) but increased the level of others (c-fos). The drug-induced lowering of mRNA levels is considered to inhibit the synthesis of proteins specifically required for G1-S transit and maintenance of the proliferation program, amplifying, thereby, the maturation signal emitted by the differentiation factors present in serum and in CM. As a result, expression of the maturation program is initiated.
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PMID:Mechanism of interaction between antineoplastic agents and natural differentiation factors in the induction of human leukemic cell maturation. 346 37

In vitro differentiation studies using the bipotential human leukemia cell line, HL60, have indicated that high levels of expression of two proto-oncogenes, c-fos and c-fms, are restricted to the myelomonocytic lineage. No such expression has been detected in induced granulocytic cells. In striking contrast to these observations, we found that c-fos mRNA levels are very high in purified human granulocytes, but barely detectable in blood monocytes and tissue macrophages. Human granulocytes contain, however, relatively low levels of c-fos protein, indicating that c-fos mRNA is inefficiently translated or that the protein is rapidly degraded in these cells. In closer agreement with the in vitro results, the level of the expression of c-fms is high in purified blood monocytes and undetectable in granulocytes. We found, however, that the evolution of monocytes into tissue macrophages is accompanied by a significant decrease in c-fms expression, suggesting that the function of c-fms is restricted to specific stages of monocytic differentiation. Our observations also show that results obtained using in vitro differentiation systems have to be regarded with caution, since they may not reflect the in vivo situation.
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PMID:Lineage-specific expression of c-fos and c-fms in human hematopoietic cells: discrepancies with the in vitro differentiation of leukemia cells. 346 21

Prolonged exposure to 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] of 2 sublines (AB-2 and AB-26) of human promyelocytic HL 60 leukemia cells produced increased adherence of the cells to the culture substratum. Advantage was taken of this property to separate physically a population of cells highly enriched in macrophage-like forms. When these differentiated cells were placed in culture medium free of 1,25(OH)2D3, there was a rapid reversal of the features of the differentiated phenotype, monitored by the loss of alpha-naphthyl butyrate esterase activity and the loss of adherence to the substrate. The reversal was accompanied by the resumption of normal rates of DNA synthesis, mitosis, and reaccumulation of c-myc and c-myb transcripts. The levels of transcripts of oncogenes c-fos and c-fms, which became abundant in the phenotypically differentiated cultures, declined along with the loss of adhesiveness and reversion to more primitive myeloblastic forms. These changes in proto-oncogene expression became evident before cell proliferation resumed, thereby excluding the diluting effect of the outgrowth of undifferentiated cells. It is concluded that in this system there is no firm commitment to terminal, as opposed to early, differentiation in the great majority of the cells and that the expression of the monocytic maturation-associated genes c-fos and c-fms is down-regulated when macrophage-like cells dedifferentiate. This strengthens the case for an association between macrophage differentiation and the expression of oncogenes c-fos and c-fms.
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PMID:Changes in proto-oncogene expression associated with reversal of macrophage-like differentiation of HL 60 cells. 347 50

To evaluate relationships between c-fos proto-oncogene expression and specific lineages of hematopoietic differentiation we analyzed the constitutive and TPA-induced expression of the c-fos gene in a wide variety of fresh human leukemic cells. High constitutive c-fos expression was detected in acute leukemias with monocytic phenotype (FAB M4/M5) and in subsets of B lymphoid leukemias, some of which coexpressed B lymphocytic and monocytic markers. Conversely, low basal levels of c-fos transcripts were found in pure acute granulocytic leukemias (FAB M1/M2/M3), in erythroleukemias (FAB M6), in the great majority of B, and in all T lymphoid leukemias. TPA-induced c-fos expression seems to correlate with monocytoid differentiation only when sustained levels of transcripts (ie, detectable for at least 24 hours) were detected. Sustained c-fos expression was in fact observed only in those myeloid or lymphoid cells that acquired a stable monocyte-like phenotype in response to the phorbol ester. These results indicate that high constitutive c-fos expression may identify myelomonocytic-oriented forms of leukemia, specific subsets of B lymphoid malignancies, and at least some cells terminally differentiated in vitro to a monocyte-like phenotype. c-fos oncogene expression can therefore be regarded as an additional marker for the subclassification of human leukemias.
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PMID:c-fos oncogene expression in human hematopoietic malignancies is restricted to acute leukemias with monocytic phenotype and to subsets of B cell leukemias. 349 89

The structure and the expression of 11 cellular oncogenes (protooncogenes) were analyzed in primary cells from 20 acute lymphocytic (ALL) and 31 acute myelogenous (AML) leukemia patients. Neoplastic cells, obtained prior to initiation of therapy, were purified and classified, on the basis of both surface antigen pattern and morphology, into pre-B, B, and T ALL and M1-M5 AML. RNA was extracted and analyzed for expression of cellular oncogenes coding for nuclear proteins (c-myc, c-myb, c-fos), the beta-chain of platelet-derived growth factor (c-sis), growth factor receptors or related proteins (c-src, c-abl, c-fes, c-erbB), or putative intermediate transducers of mitogenic signals (c-Ha-ras, c-Ki-ras, c-N-ras). Quantitative analysis of total RNA was carried out by dot blot hybridization to specific cDNA or genomic probes. Number and size of transcripts were evaluated by blot hybridization of electrophoretically fractionated poly(A)+ RNA. Expression of c-myc and c-myb was detected in all leukemic cells at variable levels and was characterized by well-defined patterns within ALL subtypes. Conversely, significant levels of c-fos transcripts were detected only in myelomonocytic (M4) and monocytic (M5) leukemias. Among the "src-family," c-fes was expressed more in AML than ALL, and c-abl was expressed at variable but not elevated levels in all leukemia types. c-Ha-ras was uniformly expressed at low levels, as in non-neoplastic cells. c-Ki-ras transcription was detected only in T ALL; N-ras expression was barely demonstrable. The structure of these protooncogenes was not grossly modified, as evaluated by Southern analysis, except for c-myc rearrangement in B ALL. These studies indicate that cellular oncogene expression in specific subtypes of leukemic cells may relate to either the proliferative activity (c-myc, c-myb) or the differentiation state (c-fos) of the cells, or possibly to expression of receptors for putative hemopoiesis-related growth factors (c-fes, c-abl). Our data provide a basis for in-depth analysis of protooncogene expression in normal and neoplastic hemopoiesis.
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PMID:Expression of cellular oncogenes in primary cells from human acute leukemias. 352 May 70

We have previously demonstrated that declines in c-myc expression precede the induction of c-fos and c-fms transcripts during monocytic differentiation of human leukemia (HL-60 and U-937) cell lines. The present study has monitored the effects of 1-beta-D-arabinofuranosylcytosine (ara-C) on proto-oncogene expression in U-937 cells. The results demonstrate that ara-C inhibits both U-937 proliferation and c-myc expression in a concentration- and time-dependent manner. At non-toxic concentrations of ara-C, these decreases in c-myc RNA occur in the absence of changes in the level of actin transcripts. The results also demonstrate that ara-C increases c-fos but not c-fms expression. Similar findings have been obtained with retinoic acid. Furthermore, although both agents induce a more mature U-937 phenotype, ara-C is a relatively weak inducer of these cells. These findings would suggest that the changes in proto-oncogene expression induced by ara-C may be related to induction of differentiation or the inhibitory effects of this agent on proliferation.
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PMID:Effects of 1-beta-D-arabinofuranosylcytosine on proto-oncogene expression in human U-937 cells. 353 6


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