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

This paper reports the molecular cloning of a rearranged c-myc region from the FT-1 cell line, which was derived from a spontaneous feline T-cell leukemia carrying the feline leukemia virus (FeLV). An abnormal c-myc EcoRI fragment of about 18 kilobases, detected by Southern blotting, was molecularly cloned from the DNA of the FT-1 cell line. The c-myc rearrangement in FT-1 was due to direct integration of the FeLV provirus genome immediately upstream of the c-myc gene in the opposite transcriptional orientation. Nucleotide sequencing showed that the LTR of this provirus had three copies of an enhancer-like sequence, unlike the sequences of FeLVs reported previously, which have only a single copy of this enhancer-like sequence.
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PMID:Molecular cloning of a feline leukemia provirus integrated adjacent to the c-myc gene in a feline T-cell leukemia cell line and the unique structure of its long terminal repeat. 253

To study the role of the protooncogene c-myb in regulating myeloid leukemia cell proliferation and differentiation, we exposed cells of the human leukemia lines HL-60, ML-3, KG-1, and KG-1a to an oligodeoxynucleotide complementary to an 18-base-pair (bp) sequence of c-myb-encoded mRNA. This treatment resulted in a significant decrease in cell proliferation in all of the lines, which was most marked in HL-60 cells. After 5 days in culture, in several separate experiments with different oligomer preparations, 75% growth inhibition was observed in c-myb antisense treated cells in comparison to untreated HL-60 cells. Two c-myb antisense oligomers of identical length with either 2- or 4-bp mismatches had no effect on cell growth nor did an 18-bp c-myb sense or myeloperoxidase antisense oligomer. The effect of a c-myc antisense oligomer (18 bp) on the growth of HL-60, KG-1, and KG-1a cells was also studied. This oligomer had much less inhibitory effect on cell proliferation than did the c-myb antisense sequence. Interestingly, although c-myc antisense treatment induced maturation of HL-60 cells while it inhibited cell proliferation, such an effect was not noted in c-myb antisense treated cells. These studies indicate that the nuclear protein encoded by the c-myb protooncogene is required for maintenance of proliferation in certain leukemia cell lines. In compared to c-myc protein suggest that, at least in HL-60 cells, c-myc amplification or N-ras activation may not be sufficient to maintain the leukemic growth in the absence of c-myb protein. These findings support the hypothesis that development and maintenance of a malignant phenotype requires a multiplicity of interrelated genetic events.
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PMID:An oligomer complementary to c-myb-encoded mRNA inhibits proliferation of human myeloid leukemia cell lines. 254 45

The molecular etiology of retrovirally induced T-cell tumors has been shown in many cases to involve proviral integration near a cellular oncogene, c-myc, N-myc, Pim-1 and pvt-1 being frequent targets for insertional activation. Murine B-cell tumors induced by infection with murine leukemia virus have been studied for rearrangements in these and other loci. In contrast to the T-cell lymphomas, tumors of the B-cell lineage, either early B-cell tumors induced in nude mice or late B-cell tumors in immunocompetent mice, did not show disruption of N-myc or Pim-1 in any of the tumors studied, although those lymphomas had acquired many new proviruses. The loci c-abl, bcl-2, fis-1, c-erbB, c-myb, and neu were likewise not involved. Rearrangement of c-myc was seen in 1 out of 71 and rearrangement of the pvt-1 locus in 4 out of 73 (5%) of the B-cell tumors. Thus it appears that mechanistic differences exist in the development of T-cell tumors and B-cell tumors caused by the same etiological agent.
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PMID:Retrovirally induced murine B-cell tumors rarely show proviral integration in sites common in T-cell tumors. 254 45

Aberrations in nuclear proto-oncogene organisation and/or gene expression have been implicated in cell transformation mediated by the v-abl gene. For example, it has been suggested that amplification of the c-myc proto-oncogene is a co-operative event in v-abl induced fibroblast transformation. We have investigated amplification of the c-myc, p53 and c-fos nuclear proto-oncogenes in several Abelson murine leukaemia virus (A-MuLV) transformed fibroblast lines. None of these proto-oncogenes were detectably rearranged or amplified in v-abl transformed Swiss 3T3 lines. In contrast, NIH3T3 fibroblasts transformed by the v-abl gene consistently showed a 4 to 16-fold amplification of the c-myc gene. These data show that c-myc gene amplification is not an obligatory event associated with A-MuLV transformation, but may be restricted to cell lines derived from NIH3T3. c-myc gene amplification also did not correlate with a reduced latency period for tumour induction in nude mice. In addition, c-myc amplification was not selected during tumourigenesis, indicating that this event is not required for A-MuLV transformed Swiss 3T3 cells to display a full tumourigenic phenotype.
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PMID:Analysis of A-MuLV transformed fibroblast lines for amplification of the c-myc, p53 and c-fos nuclear proto-oncogenes. 254 44

The administration of hydroxyurea (3 x 10(-4) M) and cytosine arabinoside (10(-7) M) greatly induces the expression of the vimentin gene in human promonocytic leukemia U-937 cells. The induction takes place at both the mRNA and protein levels, as demonstrated by Northern blot, immunoblot and immunofluorescence assays. On the contrary, the drugs inhibit the expression of c-myc and ornithine decarboxylase, and do not modify significantly the expression of beta-actin. Since hydroxyurea and cytosine arabinoside trigger the phenotypic differentiation of U-937 cells, as demonstrated by the induction of the differentiation-specific CD11b and CD11c antigens, it is concluded that vimentin expression might be implicated in the maturation of these cells.
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PMID:S-phase inhibitors induce vimentin expression in human promonocytic U-937 cells. 259 4

Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193) is a synthetic nucleoside inhibitor of inosine monophosphate dehydrogenase. This agent has recently been shown to induce differentiation of human leukemia cell lines. In the present study, we have monitored the effects of tiazofurin on differentiation and proto-oncogene expression in K562 erythroleukemia cells. Tiazofurin induced K562 cell hemoglobin production in a concentration-dependent manner. This induction of a differentiated phenotype was also associated with a loss of proliferative capacity. In contrast to the reversible effects of hemin on induction of K562 cell hemoglobin synthesis, the effects of tiazofurin were irreversible. Northern blot analysis of K562 cells treated with 10 microM tiazofurin demonstrated the accumulation of alpha- and gamma-globin mRNA. The results also demonstrate that there was little if any effect of tiazofurin on levels of c-myc, c-myb, or c-abl mRNA. Furthermore, there were no detectable changes in Ki-ras, Ha-ras or N-ras expression at the mRNA and protein levels in tiazofurin-treated K562 cells. These findings suggest that tiazofurin induces changes in levels of globin transcripts but has little if any effect on c-myc, c-myb, c-abl, or c-ras gene expression in K562 cells.
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PMID:Effects of tiazofurin on globin and proto-oncogene expression in K562 erythroleukemia cells. 263 29

Three cellular or putative oncogenes: c-myc, bcl1, and bcl2 were previously found to be rearranged in some B cell malignancies due to chromosomal translocations. Data concerning the role of such genetic rearrangements in B-CLL are very scanty and limited to few cases in which bcl1 rearrangements were found. We studied DNA samples from 38 cases of B-CLL by Southern blot technique in order to find out the existence and frequency of such events. No bcl1 or bcl2 rearrangements were found in any of the studied cases; thus, involvement of these genes in CLL must be rare. In one patient who had an aggressive and resistant disease, c-myc rearrangement was found.
Leukemia 1989 Jan
PMID:A search for bcl1, bcl2, and c-myc oncogene rearrangements in chronic lymphocytic leukemia. 264 78

The v-myc oncogenes of chicken retroviruses (including MC29) bear point mutations relative to chicken c-myc. These mutations result in several amino acid differences in the encoded proteins. We have used recombinant murine retroviruses containing various myc alleles to analyse the myelomonocytic transforming potential of the myc oncogene. The myc alleles used were MC29 v-myc, chicken c-myc, chimeric genes combining 5' sections of v- or c-myc with 3' sections of c- or v-myc, and mouse c-myc. The same retroviral vector (based on the genome of Moloney leukemia virus) was used for each allele and the genes were translated from genomic message. By infecting the primary mouse tissues, bone marrow, peritoneal-derived macrophages and mixed embryonic tissue with the recombinant viruses, variation was found in the transforming efficacy of these alleles: v-myc was most effective, followed by the two chimeric genes, whereas c-myc (chicken or mouse) was least effective in eliciting myelomonocytic transformation. Viral gag sequences were not necessary for this transformation. In each case, the transformed monocytes were growth factor-dependent and non-immortal. However, v-myc transformed monocytes (though not monocytes transformed by other myc alleles) were able to progress to an immortal, growth factor-independent phenotype. Our results indicate that v-myc is far more effective than c-myc in eliciting myelomonocytic transformation; that this is due to combinatorial effects of 5' and 3' mutations in the v-myc gene; and that secondary events in addition to these mutations are required for transformation of myelomonocytic cells to an immortal, tumorigenic phenotype.
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PMID:Transformation of murine myelomonocytic cells by myc: point mutations in v-myc contribute synergistically to transforming potential. 264 46

We report a new common proviral insertion site in murine leukemia virus-induced T cell lymphomas to be N-myc. Proviral activation of N-myc was found in 35% of independently induced primary tumors. The vast majority of the proviral insertions occur within a small segment of the 3'-untranslated region of the N-myc gene, directly downstream of the protein-encoding domain. This results in an increased level of expression of a truncated N-myc mRNA. Together with the previously shown c-myc activation we now find involvement of myc genes in greater than 75% of the primary T cell lymphomas induced by Moloney murine leukemia virus in C57BL10 and BALB/c mice, and show for the first time that N-myc can be over-expressed by a mechanism other than gene amplification.
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PMID:N-myc is frequently activated by proviral insertion in MuLV-induced T cell lymphomas. 265 9

While activation of the protooncogene c-N-ras is observed regularly in acute myelogenous leukemia, amplification of c-myc in AML cells or derived lines is uncommon. In particular, concurrent ras/myc activation, which has been shown to be critical in several elegant models of malignancy, has been demonstrated in a very small number of human tumors or derivative cell lines. A cell line, RED-3, is described which was derived from cells of a patient with aggressive acute leukemia which exhibits many markers of lineage infidelity. DNA from this cell line contains an activating point mutation of c-N-ras as well as 20-30-fold amplification of c-myc. After HL-60, this is the second example of ras/myc activation in AML derived cells and demonstrates that this lesion is not unique to HL-60. Rather, it may be important in leukemogenesis in a small proportion of AML patients.
Leukemia 1989 Jul
PMID:c-myc amplification coexistent with activating N-ras point mutation in the biphenotypic leukemic cell line RED-3. 265 2


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