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)

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

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

We report two leukemia patients with double minutes (DMs) chromosomes. Both patients were diagnosed as having acute myelocytic leukemia (AML) FAB M2. Cytogenetic analysis showed normal chromosome karyotype with 1-53 DMs chromosomes in the first patient, and complex chromosome aberrations including deletion of chromosome 8 at 8q24 region and 1-84 DMs chromosomes in the second patient who had a history of extensive radiotherapy for laryngeal cancer 8 years prior to the development of leukemia. Analysis of DNA from the two patients revealed that oncogene of c-myc was amplified about 5 to 10 folds in the leukemic cells. The other fourteen oncogene of c-myc was c-myb, c-abl and N-myc, showed no increases of gene content. Furthermore, a transforming gene, N-ras was detected in the first patient by in vivo selection assay method. This is the second report on AML patients with c-myc gene amplification and DMs chromosomes.
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PMID:[c-myc gene amplification and N-ras transforming gene in two cases of acute myelocytic leukemia with double minute chromosomes]. 269 22

The majority of patients with chronic myelogenous leukemia (CML) have a characteristic reciprocal translocation between chromosome 9 and 22, resulting in the Philadelphia (Ph1) chromosome. During this translocation, the c-abl oncogene on chromosome 9 is transferred to the Ph1 chromosome and linked to a breakpoint cluster region (bcr), which is part of a large bcr gene. This phenomenon results in the formation of a bcr-c-abl fusion gene, which is transcribed into an 8.5 kb chimeric mRNA encoding a 210 kd bcr-c-abl fusion protein. The fusion protein has tyrosine kinase activity implicated in the pathogenesis of CML. The breakpoint near the c-abl locus on chromosome 9 can occur within a large area. In contrast, the breakpoints on chromosome 22 cluster within the bcr region of 5.8 kb. A chronic phase lasts for an average of 2 to 3 years; and, subsequently, most patients enter blast crisis. In the present study, we examined 15 Ph1-positive CML patients (eight in chronic phase, one in accelerated phase, and six in blast crises) as to whether the identifiable difference in the locations of the bcr breakpoints exist between CML patients in chronic phase and those in blast crisis. In seven of eight CML patients in chronic phase, in one in accelerated phase, and in four out of six CML patients in blast crisis, the bcr breakpoints clustered in the 3' portion of the bcr. Thus, we could not find out the correlation between the locations of the bcr breakpoints and the clinical stage of the CML patients. This might imply that blastic transformation in Ph1-positive CML was caused by other mechanisms than the transition of the bcr breakpoints.
Leukemia 1989 Jul
PMID:No correlation between locations of bcr breakpoints and clinical states in Ph1-positive CML patients. 273 54

Despite the major breakthrough in the knowledge of the molecular events underlying the t(9;22) translocation, still no consistent data have been found on the evolution of Ph1 positive CML from the chronic to the accelerated or blastic phase of the disease. In most patients in fact the bcr/abl rearrangements are identical both in chronic phase and in blast crisis, and overall differences in chronic phase duration, related to different location of breakpoints inside the bcr region, were found to be marginal. We approached this problem by studying the molecular features of the bcr/abl abnormality in rare CML patients with very long, atypical chronic phase. The three patients studied, whose chronic phase duration is 17, 19, and 21 years, respectively, have typical genomic bcr rearrangements, and two of them show, hybridizing Northern blots to c-abl, the 8.5 kb mRNA, as that typically present in CML. It seems that genomic alterations within bcr and abl cannot account, alone, for the duration of the chronic phase of Ph1 positive CML and those quantitative and/or qualitative alterations of the p210 bcr/abl protein, unluckily awkward to prove, might be responsible for the atypical clinical features of these CML long survivors.
Leukemia 1989 Jul
PMID:Philadelphia-positive chronic myelogenous leukemia with typical bcr/abl molecular features and atypical, prolonged survival. 273 55

Tumor induction by treatment with polycylic hydrocarbons depends on age and the strains of rats used. Juvenile LE rats are very sensitive to the induction of leukemia and chromosomal breaks by intravenous DMBA injection. We have previously demonstrated a chromosomal translocation in chromosome 3 and 12 in a DMBA induced LE rat leukemia cell K3D. In our present communication we have examined the c-abl expression in the leukemic cell line as well as in the LE rats at different ages. We found that in the leukemic cell K3D the c-abl expression is elevated both at the level of mRNA and protein. In the preleukemic stage, highly elevated expression of c-abl mRNA was detected exclusively in the spleen of the juvenile LE rats. Furthermore this high expression of the c-abl gene correlates well with hypermethylation of possible cytosine residue in the c-abl genomic locus.
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PMID:Detection of hypermethylation of the c-abl genomic locus in the spleen of juvenile LE rats. 284 25

Abelson leukemia virus (A-MuLV) is an oncogenic murine retrovirus whose genome contains sequences homologous to those of a normal cellular gene, c-abl. It has been demonstrated to cause rapid transformation of several cell types, including pre-B lymphocytes, macrophages, and fibroblasts. More recently, A-MuLV has been reported to induce thymic tumors in a mouse strain (C57BL/Ka) previously thought to be resistant to disease induction. We showed that the masses occurring after intrathymic injection of the virus were composed of lymphocytes of a previously described immature T-cell phenotype. This phenotype has been defined here by flow cytometry of 10 primary tumor samples stained with antibodies to several thymocyte differentiation antigens. Hybridization of DNAs from these tumors with v-abl, immunoglobulin mu, and T-cell antigen receptor beta-chain probes confirmed the T-lymphoid, polyclonal nature of the primary tumor cells. The primary tumors were malignant, as clearly shown by reinjection into Thy-congenic host animals. Further, four Thy- in vitro cell lines derived from three tumors differed from the majority of primary tumor cells and were similar to previously described A-MuLV-transformed pre-B cells. The consistent T-lymphoid phenotype exhibited by primary A-MuLV thymomas may represent one stage of normal thymocyte differentiation.
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PMID:Transformation of T-lymphoid cells by Abelson murine leukemia virus. 287 33

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

We have determined the prevalence of amplification and rearrangements for c-myc, c-myb, c-mos, bcr, c-abl, c-Ha-ras-1, c-N-ras, and c-K-ras-2 in a total of 51 cases of human leukaemia (19 patients with AML, 13 cases with CML, 14 cases with ALL, and 5 cases with CLL). Amplifications at a level of more than 2 two copies per haploid genome are apparently very rare and were found only once for c-myb in a c-ALL patient. Oncogene rearrangements were not found except for bcr, which was rearranged in all cases of CML, and 5 cases of ALL studied. Restriction fragment lengths polymorphisms (RFLPs) were also analysed. A previously described rare 5 kb EcoRI allele at the c-mos locus was absent in our patients. Rare alleles at the c-Ha-ras-1 locus were found to be significantly more prevalent in our patients than in a control group. Transfection experiments revealed no dominant transforming oncogenes in the tumour DNA of 3 patients carrying such rare alleles.
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PMID:Oncogene amplifications, rearrangements, and restriction fragment length polymorphisms in human leukaemia. 288 56

Herbimycin A, a benzoquinonoid ansamycin antibiotic, is found to reduce intracellular phosphorylation by tyrosine protein kinase. The human chronic myelogenous leukemia cell line K562 expresses a structurally altered c-abl protein with tyrosine kinase activity. When K562 cells are induced to undergo erythroid differentiation by hemin, reduction in the intracellular level of tyrosine phosphorylation occurs. In order to understand the relationship between induction of differentiation and reduction of tyrosine phosphorylation by the c-abl gene product, the effect that herbimycin A, a selective inhibitor of intracellular tyrosine kinase activity, exerts on the differentiation of K562 cells was examined. Reduction of tyrosine phosphorylation in K562 cells by herbimycin A was observed within 1 h. Noncytotoxic concentrations of herbimycin A induced erythroid differentiation of K562 cells but not of murine erythroleukemia 745A cells. The other human myeloid leukemia cell lines (HL-60, THP-1, and U937) tested were not induced to undergo cell differentiation by this antibiotic. Herbimycin A and the other well-known inducers such as hemin, butyric acid, Adriamycin, and 1-beta-D-arabinofuranosylcytosine had additive or more than additive effects on induction of erythroid differentiation of K562 cells. With respect to inhibition of cell growth, the sensitivity of K562 cells to herbimycin A was highest in the human leukemia cell lines we tested. Noncytotoxic concentrations of herbimycin enhanced the antiproliferative effect of Adriamycin or 1-beta-D-arabinofuranosylcytosine on K562 cells. Combination therapy with herbimycin A and its derivatives may be considered for use in the treatment of some types of leukemia where tyrosine kinase activities are implicated as determinants of the oncogenic state.
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PMID:Induction of erythroid differentiation of K562 human leukemic cells by herbimycin A, an inhibitor of tyrosine kinase activity. 291 Apr 52


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