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

Expression of the proto-oncogene p93c-fes and its associated tyrosine kinase activity is marked in mature granulocytes, monocytes, differentiated HL-60 leukemia cells, and leukemia cell lines KG-1, THP-1, HEL, and U-937, which can be induced to differentiate along the granulocyte/monocyte pathway. Conversely, p93-c-fes expression is absent in the K562 cell line, which is resistant to myeloid differentiation. Upon transfection and clonal selection of K562 cells using a mammalian expression vector containing the 13-kilobase pair c-fes gene, c-fes mRNA was transcribed and p93-c-fes tyrosine activity kinase was expressed. Clones expressing c-fes underwent myeloid differentiation as assessed by the appearance of phagocytic activity, Fc receptors, nitro blue tetrazolium reduction, Mac-1 immunofluorescence, and lysozyme production. These results indicate that the expression of the c-fes protooncogene and its associated tyrosine kinase activity plays a major role in the initiation of myeloid differentiation.
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PMID:K562 leukemia cells transfected with the human c-fes gene acquire the ability to undergo myeloid differentiation. 265 6

We investigated the ability of the proto-oncogene L-myc to substitute for c-myc in blocking murine erythroleukemia differentiation. Murine erythroleukemia cells (line C19) were transfected with recombinant plasmids containing genomic and cDNA fragments of the L-myc gene driven by a Moloney murine leukemia virus long terminal repeat. Clones expressing constitutive high levels of L-myc failed to differentiate in response to the chemical inducer N,N'-hexamethylene bisacetamide (HMBA). The block to differentiation correlated with the level of L-myc expression. Furthermore, transfected clones grown in the presence of inducer for an extended period of time showed an increased level of L-myc expression. These results suggest that functional domains of the c-myc gene involved in differentiation are located in the discrete regions of homology between the c- and L-myc genes.
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PMID:A transfected L-myc gene can substitute for c-myc in blocking murine erythroleukemia differentiation. 266 39

The clinical association of an increased incidence of acute myelogenous leukemia (AML) with previous chemoradiotherapy, the detection of specific karyotypic changes in these secondary (therapy-induced) cases of AML and the discovery of increasing levels of oncogene-specific RNA in leukemia cells suggest that one potential site of action of environmental agents might be the proto-oncogenes in human hematopoietic stem cells. The location of human proto-oncogenes at the sites of chromosome breaks and/or translocations in cells from some patients with leukemia or lymphoma is a striking observation. These data stimulated research into the mechanism of activation of specific oncogenes that change the biology of human hematopoietic cells. Recent investigations have focused upon several areas that might alter cell biology including: 1) translocation and/or inversion of chromosome fragments containing a proto-oncogene to a location where other gene sequences can stimulate oncogene activation, 2) replication of copy number of proto-oncogenes or increased transcriptional activity and 3) point mutation in proto-oncogenes leading to a structurally altered protein. The third area of research has recently received significant attention with respect to the potential role of three ras genes (c-Harvey-ras, c-Kirsten-ras and N-ras) in human leukemias and myelodysplastic syndromes. Recent studies have proposed a model for leukemogenic transformation of human hematopoietic cells by the product of a mutated ras oncogene. Mutations at codons 12, 13 or 61 of the first exon of its 4.7 Kb of DNA (for c-Ha-ras) have been described. Other data revealing an absence of such mutations in the ras genes of many human leukemias and the absence of detectable transcription of ras genes in many alkylating agent-associated cases of AML, suggest that while ras mutations may be involved in some settings, there are probably multiple genetic pathways to leukemogenic transformation of human hematopoietic cells.
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PMID:ras mutations in human leukemia and related disorders. 268 41

The proto-oncogene c-N-ras frequently bears point mutations in ANLL cell DNA which endow it with the capacity to transform NIH/3T3 cells in vitro. Chronic myelogenous leukemia (CML) is a neoplasm highly related to ANLL since it involves the same hematopoietic progenitor cells and ultimately transforms to a neoplasm virtually indistinguishable from acute nonlymphoblastic leukemia (ANLL). Thus, we and others have examined ras genes in CML. This report confirms that ras gene activation is a very infrequent event in CML. However, a lymphoblastic cell line derived from a patient with CML did exhibit a novel second exon 61st codon activating mutation of c-N-ras.
Leukemia 1989 Nov
PMID:Infrequent ras activation in chronic myelogenous leukemia (CML): activating 61st codon mutation in the CML-derived cell line, IM-9. 268 48

Translocation t(3;21)(q26;q22) is a rare but nonrandom event occurring in Philadelphia positive chronic myeloid leukemia. We describe five new cases (two males, three females) where t(3;21) is associated with the progression of the disease. Using FACS analysis, we confirm the myeloid type of the blast crisis. High resolution chromosomal analysis allowed us to define more precisely the chromosomal breakpoints to 3q26.2 and 21q22.2, close to the respective localizations of two genes important in cell proliferation and cancer pathogenesis: the transferrin receptor gene and the ets.2 proto-oncogene.
Leukemia 1989 Aug
PMID:Translocation (3;21) in Philadelphia positive chronic myeloid leukemia: high resolution chromosomal analysis and immunological study on five new cases. 274 89

Transformation of a rat thyroid epithelial cell line (FRTL5-C12) with Kirsten and Harvey murine sarcoma viruses (carrying the ras oncogenes) results in elevated levels of three perchloric acid-soluble nuclear phosphoproteins. These three proteins are also induced to high levels in the PC-C13 thyroid epithelial cell line when transformed by the myeloproliferative sarcoma virus (carrying the v-mos oncogene) and when transformed by transfection with the c-myc proto-oncogene followed by infection with the polyoma leukaemia virus (PyMuLV) carry the polyoma middle T antigen gene. Neither c-myc or PyMuLV alone induced high levels of the three nuclear proteins. Untransformed thyroid fibroblasts have high levels of two of the three proteins and can be transformed by PyMuLV alone resulting in the appearance of the third protein. Transformation with Harvey sarcoma virus also results in the induction of the third protein. The three phosphoproteins have been purified by h.p.l.c. and shown to be related to the HeLa protein HMGI already described. The results of these studies indicate that elevated levels of these HMGI-like proteins are associated with neoplastic transformation and/or with an undifferentiated phenotype.
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PMID:Elevated levels of a specific class of nuclear phosphoproteins in cells transformed with v-ras and v-mos oncogenes and by cotransfection with c-myc and polyoma middle T genes. 282 Jul 15

The c-fms proto-oncogene encodes the receptor for the mononuclear phagocyte colony stimulating factor, CSF-1. Although the tyrosine kinase activity of the CSF-1 receptor is stimulated by its ligand, the viral oncogene, v-fms, encodes a constitutive receptor kinase that can transform both fibroblasts and hematopoietic cells by a nonautocrine mechanism. Mutations in the c-fms gene as well as a critical alteration of the distal 3' coding sequences appear to be responsible for fully activating its latent transforming potential. The v-fms gene can convert CSF-1 or IL-3 dependent hematopoietic cell lines to factor independence and render them tumorigenic. Expression of the v-fms gene product does not transmodulate the normal receptors for CSF-1 or IL-3 and affects neither their affinity, number, nor potential to be independently down-regulated by their ligands or by phorbol esters. The ability of v-fms to transform hematopoietic target cells suggests that critical alterations in the c-fms proto-oncogene might similarly contribute to leukemia.
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PMID:Fibroblast and hematopoietic cell transformation by the fms oncogene (CSF-1 receptor). 282 35

The macrophage colony stimulating factor, CSF-1 (M-CSF) exerts its pleiotropic effects on hematopoietic cells of the mononuclear phagocyte series by binding to a single class of high affinity receptors encoded by the c-fms proto-oncogene. Binding of CSF-1 to its receptor activates an intrinsic tyrosine kinase activity, resulting in autophosphorylation of the receptor on tyrosine, rapid receptor down modulation, and phosphorylation of as yet unidentified physiologic substrates that initiate a mitogenic response. Transduction of a human CSF-1 receptor cDNA into mouse fibroblasts enables them to proliferate in response to human recombinant CSF-1, suggesting that the receptor gene contains all the information necessary to elicit a mitogenic response, even in cells which do not normally respond to the growth factor. The v-fms oncogene product has undergone genetic alterations which constitutively activate the receptor kinase in the absence of CSF 1. Insertion of the v-fms gene into macrophage or immature myeloid cell lines abrogates their dependence on hematopoietic growth factors and renders them tumorigenic in nude mice. Reconstitution of lethally irradiated mice with bone marrow stem cells containing the v-fms oncogene also induces clonal proliferation and, ultimately, frank malignancies of multiple hematopoietic lineages. Thus, constitutive activation of the CSF-1 receptor gene, either by mutation or gene rearrangement, might be expected to contribute to leukemia.
Leukemia 1988 Dec
PMID:The role of the CSF-1 receptor gene (C-fms) in cell transformation. 284 91

A common site of ecotropic murine leukemia virus integration designated Evi-2 (ecotropic viral integration site-2) has been identified in BXH-2 myeloid tumors. As part of experiments to determine whether Evi-2 identified a new proto-oncogene locus involved in myeloid disease, we determined its chromosomal location. We mapped Evi-2 to mouse Chromosome 11 using standard recombinant inbred strain and genetic backcross analysis. We then determined the location of Evi-2 relative to other proto-oncogene and growth factor loci located on Chromosome 11 by interspecific backcross analysis. The loci included in this study were the proto-oncogene loci, Erbb, Erba, and Rel, as well as, Il-3 (interleukin-3), Csfgm (granulocyte-macrophage colony stimulating factor), and Trp53-1 (transforming protein p53). All loci except Erbb had been previously mapped to Chromosome 11 with the use of somatic cell hybrids and consequently their positions on Chromosome 11 were not known. One proto-oncogene, Erbb-2 (analogous to the neu proto-oncogene), and one growth factor locus, Csfg (granulocyte colony-stimulating factor), which had not been mapped in the mouse were also localized on Chromosome 11 using the interspecific backcross mice. Recombination between Evi-2 and all proto-oncogene and growth factor loci was demonstrated, suggesting that Evi-2 may ultimately identify a new proto-oncogene involved in myeloid disease. This study revealed a number of interesting conserved linkage groups common to mouse and man.
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PMID:Localization of Evi-2 to chromosome 11: linkage to other proto-oncogene and growth factor loci using interspecific backcross mice. 285 Nov 24

Oncogene abnormalities are thought to have a central role in some human malignant disorders, particularly Burkitt leukaemia/lymphoma and chronic myeloid leukaemia (CML). However, the extent to which specific oncogene changes determine the clinical features of these disorders is unknown. This question was studied in two groups of patients with CML negative for the Philadelphia (Ph) chromosome; one group showed clinical features typical of Ph-positive CML and the other group lacked such features. Molecular findings were compared with those of Ph-positive CML. In all ten patients there was evidence for rearrangement of the bcr (breakpoint cluster region) gene. In the four cases studied the c-abl proto-oncogene was translocated to chromosome 22 and in five cases there was transcription of a chimeric bcr-abl mRNA. Thus, the molecular abnormality is the same in both groups of Ph-negative CML and identical to that in Ph-positive CML. Factors other than the bcr/c-abl rearrangement must underlie the clinical heterogeneity of CML.
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PMID:Do oncogenes determine clinical features in chronic myeloid leukaemia? 288 97


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