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)

A class of mouse neoplasms termed Abelson virus-induced plasmacytoid lymphosarcomas has previously been found to express abnormal myb transcripts due to a helper virus insertion into the 5' end of the c-myb locus. We have established clonal cell lines from these tumors and have shown that they all express markers characteristic of myelomonocytic, rather than lymphoid, cells. Treatment of the plasmacytoid lymphosarcoma lines with phorbol 12-myristate 13-acetate led to various degrees of growth arrest, presumably due to myelomonocytic differentiation. To date, characterization of myeloid cell lines with varying responses to phorbol 12-myristate 13-acetate has not been reported. The different clonal plasmacytoid lymphosarcoma lines should, therefore, provide a good model to help elucidate the role of altered myb locus and other protooncogenes in myelomonocytic leukemia. Contrary to studies on induced differentiation of myelomonocytic cells with normal myb locus, our results on plasmacytoid lymphosarcoma cells indicate that reduced myb and myc expression may not be obligatory for growth arrest to occur. The present study, however, supports the previous notion that the myb transforming ability may be restricted to cells of the myelomonocytic lineage. In addition, we found that only the more mature cells can undergo prolonged phorbol 12-myristate 13-acetate-induced growth arrest, suggesting that the maintenance of these leukemic cells in their proliferative state, presumably by the myb gene product, can be overcome with appropriate differentiation signal(s).
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PMID:Phorbol ester-induced growth arrest of murine myelomonocytic leukemic cells with virus-disrupted myb locus is not accompanied by decreased myc and myb expression. 302 54

Antibodies were prepared against bacterially expressed polypeptides corresponding to various portions of the v-ets-encoded domain of P135gag-myb-ets, the transforming protein of avian leukemia virus E26. Immunoprecipitation analyses show that ca. 80 v-ets-encoded amino-acids located immediately after the v-myb/v-ets junction are not found in P54/56c-ets, the translation product of the c-ets proto-oncogene, nor in a set of cellular proteins of 64, 62, and 60 kDa related to but distinct from P54/56c-ets. In addition, Northern blot analyses show that these 5' v-ets sequences neither derive from the nontranslated region of the known cellular transcripts hybridizing to a v-ets probe nor from the c-myb transcript or the helper virus genetic information. Tryptic peptide analyses furthermore indicate that, except for these sequences and the last 16 carboxy terminal amino acids of P135gag-myb-ets, the amino acids encoded by v-ets are essentially colinear with those of P54c-ets.
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PMID:The 5' extremity of the v-ets oncogene of avian leukemia virus E26 encodes amino acid sequences not derived from the major c-ets-encoded cellular proteins. 302 65

Dsi-1 is a region of chromosomal DNA that underwent proviral insertion in 3 of 24 Moloney murine leukemia virus-induced rat thymomas. In one of these tumors, a provirus is also integrated adjacent to the proto-oncogene c-myc. The proviruses in Dsi-1 have been characterized and appear to be complete. The proviruses were located within a 2-kilobase region that contained four prominent DNase I-hypersensitive sites. These hypersensitive sites were observed in Moloney murine leukemia virus-induced thymomas but not in NRK cells. The region of Dsi-1 immediately 3' to the insertions cross-hybridized with human and chicken DNA, indicating that it contains highly conserved sequences. No evidence could be found for the expression of this highly conserved region. Dsi-1 was mapped to mouse chromosome 4. This location demonstrates that Dsi-1 is different from 16 of the known proto-oncogenes (c-abl, c-erbA c-erbB, c-ets-1, c-ets-2, c-fes, c-fos, c-myb, c-myc, c-raf, A-raf, c-Ha-ras, c-Ki-ras, N-ras, c-sis, and c-src) and 12 cellular regions of tumor-associated integrations in retrovirus-induced tumors (c-erbB, Fis-1, int-1, int-2, Mis-1/pvt-1, Mlvi-1, Mlvi-2, c-mos, c-myb, c-myc, Pim-1, and c-Ha-ras). Hybridization experiments indicated that Dsi-1 is probably different from five additional proto-oncogenes (c-fgr, c-fms, c-mos, neu, and c-yes) and from two additional frequent integration regions (lck and Mlvi-3).
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PMID:Dsi-1, a region with frequent proviral insertions in Moloney murine leukemia virus-induced rat thymomas. 302 11

Proto-oncogenes are thought to be involved in cellular differentiation and proliferation. Tumor necrosis factors (TNFs) are specific cytokines that have cytostatic and cytotoxic effects in vitro against a wide range of human tumor cells. We have previously demonstrated that recombinant TNFs (rTNFs) have an antiproliferative effect on certain human leukemic cell lines (HL-60, KBM3, KBM5) and no effect on others (K562). To study the possible role of the c-myc and c-myb oncogenes in this antiproliferative effect of TNF, we examined their expression in cell lines HL-60, KBM3, KBM5, and K562 before and after incubation with rTNF-alpha. Expression of c-myc and c-myb was elevated in all cell lines prior to incubation with rTNF-alpha. In the sensitive cell lines HL-60, KBM5, and KBM3 expression of c-myc and c-myb decreased rapidly 8-, 16-, and 4-fold, respectively, by 24 hr. K562 cells, insensitive to rTNF-alpha, exhibited no change in c-myc or c-myb expression over 24 hr. These studies demonstrated that down-regulation of c-myc and c-myb expression were associated with antiproliferative effects of rTNF-alpha on these cell lines.
Leukemia 1988 Nov
PMID:Suppression of c-myc and c-myb expression in myeloid cell lines treated with recombinant tumor necrosis factor-alpha. 305 50

The influence of interferon-alpha 2 (IFN-alpha 2) on the mRNA levels of cellular proto-oncogenes was studied in malignant cells from patients with chronic lymphocytic leukemia (CLL). These cells can be induced to blast transform, differentiate and, in some cases, proliferate upon exposure to IFN. Treatment with IFN-alpha enhanced the levels of c-myc mRNA in malignant cells from the patients, whereas the levels of c-myb mRNA decreased, as measured by slot blot hybridizations. In cells from some patients, an enhanced expression of c-fos and k-ras was observed following exposure to IFN-alpha. No major effect on the expression of c-raf or of enolase was observed in any of the patients following exposure to IFN-alpha, whereas the levels of beta 2-microglobulin mRNA increased. In contrast to the observed effects on oncogene expression in CLL cells, IFN had no major effect on the expression of any of the tested oncogenes in lymphocytes from healthy donors or in B-cells from three neoplastic cell lines (380, FL18, RS). We conclude that IFN-alpha can enhance or repress the expression of several oncogenes in nondividing primary malignant cells from patients with leukemia. We also show that the response of malignant cells from patients to IFN-alpha is different than that seen with neoplastic cell lines which represent a similar stage of B-cell differentiation.
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PMID:Influence of interferon-alpha on the expression of cellular oncogenes in primary chronic lymphocytic leukemia cells. 306 Jul 97

The authors have assayed the level of expression of several cell-cycle related genes in several populations of circulating myeloid leukemic blast cells. The genes explored included oncogenes such as c-myc, c-myb, p53, and cell-cycle-related genes such as vimentin, calcyclin, ornithine decarboxylase (ODC) and histone H3. Particular attention was given to analysis of the relationship existing between the mRNA levels of the histone H3 gene, which is expressed specifically in the S phase of the cell cycle, and the levels of other genes that are expressed in different stages of the G1 phase. Remarkable differences were observed among the different cases indicating that a differential expression of cell-cycle-related genes characterizes many acute leukemias. This differential expression is reflected in an altered ratio among G1-related genes and the H3 histone gene. The large fraction of leukemic cells which does not express histone H3 and therefore is functionally noncycling, shows a heterogeneous pattern of G1-related gene expression. This reflects the inability of most leukemic cells to progress through the G1 phase into the S phase of the cell cycle. This inability represents an abnormality of the cell cycle. It is concluded that the study of the expression of cell-cycle genes and protooncogenes in in understanding how leukemic cells enter a state of proliferation arrest, which appears to occur in a large fraction of leukemic cells.
Leukemia 1988 Dec
PMID:Expression of oncogenes and cell cycle related genes in acute and chronic leukemias. 319 78

The v-myb, ets-containing avian leukemia virus E26 is unique in its capacity to transform both erythroblasts and myeloblasts. Previous studies showing that v-myb is sufficient for the transformation of myeloid cells failed to definitively establish the role of the v-ets gene. We have now isolated a mutant of E26, ts1.1, that is temperature-sensitive for erythroid cell transformation and that we found to contain a single mutation in the v-ets gene. Surprisingly, myeloid cells transformed by this mutant showed an altered phenotype relative to wild-type-transformed cells, in that they resemble promyelocytes. In addition, infection of mature macrophages with ts1.1 led to their transformation and conversion into promyelocyte-like cells. We conclude that the v-ets domain of the p135gag-myb-ets protein of E26 has an effect on both erythroid and myeloid cell differentiation, suggesting a possible role for the c-ets/c-myb genes in the commitment of hematopoietic cells towards specific lineages.
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PMID:A single point mutation in the v-ets oncogene affects both erythroid and myelomonocytic cell differentiation. 320 83

The highly conserved, single copy c-myb gene has been independently transduced by two avian acute leukemia viruses, AMV and E26. This gene has also undergone insertional mutagenesis by non-acutely transforming murine leukemia viruses in a number of hematopoietic tumors. The common denominator of these retroviral activations of c-myb appears to be truncation of the normal coding region at either or both ends. The role of point mutations in myb-induced leukemogenesis is currently unknown. The products of the c-myb gene and its altered viral counterparts are nuclear proteins, a large fraction of which are associated with the nuclear matrix. In addition, the myb gene products have short half-lives and bind DNA in vitro. These features suggest that myb may act by regulating DNA replication or transcription. Consistent with this notion, the expression of c-myb is cell cycle dependent in several cell types. However, the abundant expression of c-myb in the thymus is not similarly regulated and may serve a different function. The expression of c-myb appears not to be limited to hematopoietic tissues as previously thought and the nature of the hematopoietic specificity of transformation by v-myb is not currently understood. Nevertheless, hematopoietic growth factors and their receptors appear to play an important role in such transformation. Two new experimental systems for studying myb have recently been described. First, the discovery of a myb-related gene in Drosophila should allow the application of powerful classical and molecular genetic approaches. The functional similarity of this distantly related gene to the much more closely related avian and mammalian myb genes is unknown. Second, recent studies of murine myb in normal and abnormal hematopoiesis offers several advantages relative to the avian system, such as in-bred animal strains, a wealth of specific cell-surface markers, and cloned hematopoietic growth factor and receptor genes. Isolation or construction of an acutely transforming murine myb retrovirus may thus be very useful. Several obvious goals for future research will be to define the function of myb proteins within the nucleus, to understand the regulation of myb expression during the cell cycle, to establish which molecular alterations are essential for converting c-myb into a transforming gene, and the determine the role of myb in human malignancies.
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PMID:The myb oncogene. 333 62

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

WEHI-274 is a monocytic leukemia that arose in a BALB/c mouse infected with Abelson murine leukemia virus. A series of subclones were derived from early passages of this tumor. Three subsets of these leukemogenic subclones were identified. Two subsets demonstrated autostimulatory patterns of growth. This was due to the ectopic production of the T-cell lymphokine the panspecific hemopoietin IL-3 in one case and of the T-cell lymphokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in the other. The third type of subclone did not secrete any autostimulatory growth factor. In the subclone producing IL-3, one copy of IL-3 gene was rearranged and abnormal IL-3 RNA transcripts were present in the nucleus. Subclones producing GM-CSF also contained abnormal GM-CSF RNA transcripts, although no rearrangement of the GM-CSF gene was detected. All three sets of subclones shared a common rearrangement of one c-myb oncogene, suggesting that they share a common ancestor. These results suggest that initiation or progression of leukemogenic behavior in this abnormal clone occurred in three different ways, two of which involved autostimulation by the ectopic activation of T-cell lymphokine genes.
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PMID:Autostimulatory mechanisms in myeloid leukemogenesis. 347 68


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