Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deregulated c-myc expression, as a consequence of translocation of the c-myc gene to one of the immunoglobulin loci, appears to play an important role in the pathogenesis of several B-cell tumors, including Burkitt's lymphoma, mouse plasmacytoma and rat immunocytoma. This study investigated the expression of c-myc and 2 other members of the myc gene family, L- and N-myc, at the mRNA and protein level, and analyzed for possible rearrangements of these genes in the human counterpart to the mouse plasmacytoma--multiple myeloma (MM). Nine well-characterized MM cell lines were examined by using Northern- and Southern-blot analysis and immunoprecipitation. The c-myc gene was found to be highly expressed in most MM cell lines. The level of expression was comparable to that observed in the COLO 320 and HL-60 cell lines, carrying amplified c-myc genes, and to that of B-cell lines with a higher proliferative activity than the MM cell lines. In the U-266 MM cell line, L-myc, but no c-myc mRNA or protein, was found. The L-myc gene was expressed in both early- and late-passage U-266 cells, suggesting that the L-myc expression was not the result of the in vitro cultivation. N-myc was not expressed in any of the MM cell lines. No rearrangements of c-myc or L-myc genes were found. We thus conclude that (a) in contrast to the corresponding mouse and rat B-cell tumors, c-myc is not frequently rearranged in MM; (b) c-myc is highly expressed in most MM lines; and (c) L-myc but not c-myc is expressed in the U-266 MM cell line.
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PMID:Expression of myc-family genes in established human multiple myeloma cell lines: L-myc but not c-myc gene expression in the U-266 myeloma cell line. 156 31

Oncogene analyses of four human myeloma cell lines provided no indication of gene amplification or rearrangement using DNA probes for the met, raf, abl, mos, erb B, Her-2-neu, fos, myb-7, fms, L-myc, sis, and myb-1 genes. However, a consistent elevation of up to 23-fold in the level of c-myc mRNA was observed in all of the cell lines studied. No restriction fragment length polymorphism (in exons one, two, or three) or c-myc gene amplification has as yet been demonstrated to account for the c-myc mRNA elevation. The c-myc mRNA has a half-life of 25 min which is comparable to that observed in other systems. The elevation in c-myc mRNA is further evidence for the role of the c-myc proto-oncogene in the pathogenesis of myeloma.
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PMID:Elevated c-myc messenger RNA in multiple myeloma cell lines. 198 Feb 37

Alteration and abnormal expression of the c-myc oncogene were investigated in human multiple myeloma. Human myeloma cells were highly purified (more than 95%) from bone marrow aspirates in 14 cases of advanced multiple myelomas and one case of plasma cell leukaemia. Southern blotting revealed that a rearranged configuration of c-myc gene was found in only one case of them, but this was a novel truncation of the gene in its coding exon II; a rearranged 3.4 kb band was detected by digestion with Xba I using c-myc exon II probe, but no rearranged band was found using exon III probe. In this case, the truncated c-myc allele was not transcribed; normal sized (2.4 kb) c-myc mRNA was markedly expressed, but no aberrant mRNA was detected. On the other hand, by Northern blotting, the nine cases, including the case with the rearranged c-myc gene, showed increased expression of normal sized (2.4 kb) c-myc mRNA. Elevated c-myc mRNA expressions were well related to the in vitro proliferation (3H-TdR uptake), but not to IL-6 response. Interestingly, extremely high expressions of c-myc mRNA were detected in two cases of aggressive myelomas, including the case with the rearranged c-myc gene, and in one of plasma cell leukaemia. These two cases of aggressive myelomas were the ones who showed the markedly high 3H-TdR uptakes, and had the common clinical features with the formation of an extramedullary mass and very short survival. These results suggest that the activation of c-myc gene could induce high proliferative activities and the subsequent aggressive transformation of myeloma cells.
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PMID:Increased expression of the c-myc gene may be related to the aggressive transformation of human myeloma cells. 202 78

The c-myc gene plays a pivotal role in mediating the competence state for cell cycle transversion. This biologic role is in contradiction to reports of elevated expression of the gene in multiple myeloma, a tumor with restricted self-renewal capacity. To more clearly define the role of this gene in plasma cells of myeloma patients, c-myc messenger RNA (mRNA) and/or oncoprotein expression were semiquantitatively analyzed on the single cell level in 19 cases of multiple myeloma, among them 1 biclonal case and 1 case with coexistent chronic lymphocytic leukemia (CLL). Performing anti-sense/mRNA in situ hybridization, mature c-myc gene transcripts were detected in 92% (12 of 13) of cases and could definitely be attributed to the plasma cells by our study. The number of Ki 67-positive plasma cells actively passing the cell cycle was less than 1% and independent of c-myc gene expression. However, because the presence of the 152-c-MYC epitope was correlated to extent of marrow plasmacytosis (r = .64; P = .043) and content of plasmablasts (P = .09), the c-myc gene might serve a function different from proliferative activity, but also associated with tumor cell mass. In CLL cells (21 of 22 cases) and their benign counterparts, ie, bone marrow and peripheral blood lymphocytes, the anti-sense/c-myc mRNA hybridization signals remained below the threshold considered as cutpoint between negative and positive. The low amounts of c-myc transcripts were correlated to neither stage of disease (P = .52) nor lymphocyte counts (P = .24). Because the numbers of peripheral blood lymphoma cells were independent of tumor mass and of c-myc gene transcripts expressed, peripheral blood lymphocytosis might more likely reflect homing processes than proliferative activity in CLL.
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PMID:Expression of the c-myc proto-oncogene in multiple myeloma and chronic lymphocytic leukemia: an in situ analysis. 207 52

Genetic alterations that lead to the clonal expansion of differentiated cells in multiple myeloma have still to be elucidated. Many chromosomal aberrations have been found, but until now, none of them is typically associated with multiple myeloma. In search for genetic defects in multiple myeloma we studied the structure and expression of the c-myc oncogene and the pvt-like region because of their frequent association with other B-cell malignancies. Here we report co-amplification of the c-myc oncogene and the 5' part of the pvt-like region in two out of 26 cases of multiple myeloma. In both cases only kappa-light chains were produced. The amplification also manifested itself at the RNA level. Total RNA was analysed in one of these two cases showing abundant c-myc mRNA. In the same RNA sample we also detected a strong hybridizing band of about 7 kb, when the pSS.4 probe, representing the 5' part of the pvt-like region, was used. This band was not present in total RNA from normal bone marrow cells or bone marrow from multiple myeloma patients without the amplification of c-myc and the pvt-like region. Until now, transcripts of the pvt-like region were only found in a few human cell lines ranging in size from 1 to 11 kb. This is the first case in which a high expression of a +/- 7 kb transcript of the pvt-like region has been found in freshly obtained tumor material probably due to a pvt-amplification. The occurrence of abnormalities in the c-myc and the pvt-like region in multiple myeloma is a rare event and may be associated with the progression of this type of tumor.
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PMID:Amplification of the c-myc and the pvt-like region in human multiple myeloma. 221 59

A complex translocation has interrupted the third exon of the c-myc gene in human plasma cell myeloma tumor cells and a derivative cell line (NCI-H929). As a result of this rearrangement, a chimeric mRNA is expressed which commences 5' of the c-myc coding region and includes sequences introduced by the translocation event. All of the detectable c-myc-containing mRNA in the tumor and cell line was derived from this rearranged c-myc allele. This chimeric c-myc mRNA, in which most of the germ line c-myc 3' untranslated region has been replaced, was greater than sevenfold more stable than c-myc transcripts with intact 3' ends. This suggests that the 3' untranslated region may play an important role in c-myc mRNA stability.
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PMID:Complex translocation disrupts c-myc regulation in a human plasma cell myeloma. 327 65

The control of c-myb mRNA abundance was examined in three representative cell lines, (the erythroleukaemia F4-12B2, the myeloma MOPC-31C and the fibroblast NIH3T3), which display abundant, low and undetectable levels of this transcript, respectively. We observed a small difference in half-life between F4-12B2 and MOPC-31C c-myb mRNA (175 min and 105 min, respectively) insufficient to account for the approximately 20-fold lower levels of this transcript in myelomas. Using the run-on transcription assay we found that c-myb transcripts were initiated at similar rates in all three cell types and were elongated at this relatively high rate to a site approximately 2 kilobases into the first intron. NIH3T3 c-myb transcripts did not proceed detectably beyond this pause/attenuation site, while in F4-12B2 cells transcription of regions 3' of this site occurred at a rate approximately 12-fold greater than in MOPC-31C. We have concluded that this transcriptional arrest mechanism, together with small differences in RNA turnover, were sufficient to account for the spectrum of c-myb mRNA abundance observed. Despite evidence of transcript initiation, we were unable to detect c-myb mRNA in fibroblasts, even under conditions (e.g. serum stimulation) which induced high c-myc mRNA levels. However, a novel 3.0 kilobase transcript with homology to c-myb was detected in cycloheximide-treated NIH3T3 cells.
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PMID:A transcriptional arrest mechanism involved in controlling constitutive levels of mouse c-myb mRNA. 328 Oct 94

We describe a 53-year-old male patient with multiple myeloma (IgA, kappa) who showed massive intramuscular tumors and hyperamylasemia of the salivary (S) type 10 months after initial diagnosis. Suspension culture of the abnormal plasma cells in the pleural fluid showed the production of S-amylase, which was confirmed by the expression of S-amylase mRNA comigrating with salivary gland mRNA. Cytogenetic analysis of the cells showed common abnormalities 1p+q-and 8q+. They expressed IL-6 mRNA, but not c-myc mRNA. Neither structural abnormality nor amplification was detected in the alleles of S amylase, and c-myc using Southern blot analysis. All of the eight patients with plasma cell dyscrasia with hyperamylasemia reported so far (including the present one) are Japanese, and showed S-type hyperamylasemia and extramedullary tumor formation at initial diagnosis or during the course of the disease. All of the four patients in whom cytogenetic analysis was performed had structural abnormalities of chromosome 1, on which the S-amylase gene is known to be located, although the break point were variable.
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PMID:[Amylase-producing plasma cell dyscrasia. Genomic analysis in a case of intramuscular tumor formation and a review of the literature]. 768 94

The expression of 6 different oncoproteins and 2 tumour suppressor gene products in the plasma cells of 63 bone marrow samples was used to determine a profile of the oncogenic phenotype of patients with multiple myeloma. Dual label flow cytometry after periodatelysine paraformaldehyde fixation was used to detect cell surface phenotype and intracellular protein expression simultaneously. The normal range for both the incidence and intensity of expression was determined for each protein by analysing plasma cells (high CD38 intensity) in 22 normal bone marrow samples. The percentage of myeloma patients with a greater than normal incidence of plasma cells expressing these proteins was 53% for c-myc, 28% for Rb, 28% for bcl-2, 27% for c-fos, 24% for p53 wild, 22% for p53 mutant, 13% for c-neu and 13% for pan-ras. When a panel of 8 antibodies was used, 82% of the samples (n = 28) had an increased incidence of expression by at least one oncoprotein or tumour suppressor gene product. The 5 patients with a normal incidence of expression of all 8 proteins were in plateau stage and 4 had not received chemotherapy for more than 12 months. The number of patients with an increased incidence of expression by 2 or more oncoproteins was significantly greater (X2 = 9.0; p < 0.005) in progressive disease (55%) than in stable disease (14%) but there was no specific phenotype pattern associated with progressive disease. All 6 oncoproteins and both tumour suppressor gene products had a greater incidence and intensity of expression in progressive than in stable disease. The expression of c-myc oncoprotein correlated with c-myc mRNA expression in the same samples (n = 10) but c-myc did not correlate with either the plasma cell labelling index (r = -0.15) nor serum thymidine kinase (r = 0.10). Our results suggest that there is a heterogeneous, non-systematic but almost universal presence of activated oncogenes and tumour suppressor genes in the plasma cells of patients with multiple myeloma and that disease progression is associated with the accumulation of a variety of secondary genetic changes which confer increased malignant behaviour.
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PMID:The oncoprotein phenotype of plasma cells from patients with multiple myeloma. 769 21

Multiple myeloma (MM) is a malignant proliferation of bone marrow plasma cells. Molecular analyses of the involvement of oncogenes (c-myc, and N- and K-ras genes) and suppressor gene (p53) in pathogenesis of MM have been recently carried out. Relatively high incidence of elevated expression of c-myc mRNA have been found, although the gene rearrangements are very rare. Mutations of N- and K-ras genes have been found in about 1/3 of patients with MM. Point mutations of p53 gene were detected in about 10-20% of patients. The mutations were found in terminal or leukemic phase of the disease. These indicate that oncogenes and suppressor genes are involved in the development and progression of MM.
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PMID:[Molecular analysis of multiple myeloma cells]. 769 86


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