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)

It has been demonstrated that interleukin-6 (IL-6) is a cytokine regulating immune response, acute-phase reaction and hematopoiesis. The deregulated expression of IL-6 was suggested to be actually involved in the pathogenesis of polyclonal B cell activation and autoimmune diseases such as rheumatoid arthritis. It could be hypothesized that continuous polyclonal B cell activation may be eventually leading to the generation of plasmacytoma/myeloma, possibly with additional expression of oncogene(s) such as c-myc gene. Therefore, future studies on the gene regulation of IL-6 would provide critical informations on the molecular pathogenesis of these diseases. Furthermore, IL-6 could be used as anti-cancer drug in certain tumors. Moreover, inhibitors of IL-6 such as anti-IL-6 monoclonal antibodies or soluble forms of IL-6 receptors could be useful in the treatment of such polyclonal/monoclonal B cell abnormalities.
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PMID:Interleukin-6: possible implications in human diseases. 266 8

The frequency of ras (H-, K-, and N-ras) and c-myc oncogenes was investigated in multiple myeloma (MM). By means of the polymerase chain reaction (PCR)/oligonucleotide hybridization method, DNA from 56 tumor biopsies was analyzed for the presence of activating mutations involving codons 12 and 61 of the H-, K-, and N-ras genes and codon 13 of the N-ras gene. Mutations, involving the N- or K-ras genes, were detected in 18 of 56 (32%) cases of which 12/43 (27%) were at diagnosis and 6/13 (46%) were after treatment. In some cases, multiple mutations affecting different ras alleles were detected. Direct nucleotide sequence analysis of PCR products indicated that a more heterogeneous nature of the base pair changes than previously shown for other tumors along with a preferential involvement of N-ras codon 61. The heterogeneity of MM cases with respect to the presence of ras oncogenes prompted an analysis of possible correlations with different clinico-pathologic characteristics of MM from which a correlation between the presence of ras oncogenes and a partial or complete lack of response to therapy emerged. The frequency of activating rearrangements or mutations of the c-myc gene were studied by Southern blot analysis and PCR sequencing, respectively. However, contrary to previous reports involving mostly MM cell lines, no structural alterations of the c-myc gene were found. These results indicate that ras, but not c-myc, oncogenes are activated in vivo in MM cells, representing the first oncogene alteration that has been associated at appreciable frequency with this type of malignancy. While the mechanism of occurrence and biological role of ras activation in MM remains to be elucidated, the preliminary correlations observed in this study between the presence of ras oncogenes and poor therapeutic response suggest that further investigations of the possible prognostic significance of these alterations are necessary.
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PMID:Ras oncogene mutation in multiple myeloma. 268 17

The characteristics of a human cell line (LP-1) derived from the peripheral blood of a patient with IgG-lambda myeloma in leukemic transformation are described. The cells resemble immature plasma cells in that they exhibit a membrane phenotype that is intermediate between late B lymphocytes and plasma cells, even though they secrete IgG-lambda chains. Treatment of LP-1 cells with 12-0 tetradecanoylphorbol-13-acetate (TPA) or pokeweek mitogen (PWM) induces the appearance of surface markers and ultrastructural features typical of mature plasma cells but does not affect their proliferative activity. Molecular analysis of the cell line showed an increased expression of the c-myc protooncogene and the presence of abnormally sized transcripts. Conventional cytogenetics and pulsed-field gel electrophoresis showed no structural rearrangements of the c-myc gene, suggesting that the abnormal c-myc expression may be due to point mutations or small deletions within the gene. The LP-1 cell line is a useful model in which to study the process of B-cell maturation; such study may lead to the uncovering of unusual mechanisms of c-myc activation. Furthermore, the LP-1 cell is a potential partner in the generation of human hybridomas.
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PMID:The human myeloma cell line LP-1: a versatile model in which to study early plasma-cell differentiation and c-myc activation. 278 66

We have examined primary leukemia cells from multiple myeloma and plasma-cell leukemia patients for rearrangement, amplification and expression of c-myc oncogene. No rearrangement or detectable amplification of the c-myc could be found in 21 cases of multiple myeloma. In contrast, 2/3 cases of plasma-cell leukemia showed amplification of the oncogene with concomitant higher level of expression.
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PMID:Amplification of the c-myc oncogene in human plasma-cell leukemia. 286 25

The methylation state of CCGG sites in and around the human ornithine decarboxylase gene, oncogenes c-myc and erb-A1, and actin genes were determined in human malignant leucocytes from patients with acute and chronic myeloid leukemia, chronic lymphatic leukemia, polycythemia vera, and multiple myeloma by means of isoschizomeric restriction endonuclease analysis. When compared with DNA from leucocytes of healthy controls, the ornithine decarboxylase and erb-A1 genes were substantially hypomethylated in all samples obtained from patients with chronic lymphatic leukemia. Hypomethylation of genes, particularly growth-related sequences, might be a crucial fact in the malignant transformation of human leucocytes. Its relatively simple detection from blood samples may prove clinically applicable in monitoring patients with chronic lymphatic leukemia.
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PMID:Hypomethylation of ornithine decarboxylase gene and erb-A1 oncogene in human chronic lymphatic leukemia. 290 92

Mammalian DNA contains several families of highly repeated sequences, some of which have been suggested to be mobile elements. We have screened tumour tissue for the rearrangement of cellular oncogenes and found evidence for the behaviour of repetitive DNA sequences as transposable elements which may activate oncogenes. In the mouse myeloma NSI and XRPC24 we found that intracisternal A particle genome was inserted into the coding region of c-mos. In both cases the rearranged c-mos was transcriptionally activated and was also able to transform NIH 3T3 cells. In the canine transmissible venereal tumour we found that c-myc was rearranged due to the insertion of an 1.8 kilobase pair cellular DNA. Nucleotide sequence analysis demonstrated that the inserted piece is 60% homologous to the monkey KpnI element which is a representative of the LINE group.
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PMID:Activation of oncogenes by transposable elements. 302 23

Bone marrow plasma cells of patients with myeloma are frequently aneuploid, have a high RNA content and typically show monoclonal immunoglobulin in their cytoplasm. Kappa-lambda co-expression in aneuploid tumor cells was restricted to patients with IgG lambda myeloma. Immunophenotype studies revealed early B cell expression often in association with mature B cell markers. Chromosomal aberrations were complex with a predominance of numeric but also structural lymphoma-type translocations; the latter were most prevalent in IgA myeloma. Specific translocations such as t(8;14) and t(11;14) were accompanied by aberrations of c-myc and bcl-l cellular genes. Effective salvage programs have been developed for melphalan-prednisone refractory myeloma. In comparing high-dose dexamethasone with vincristine-adriamycin + dexamethasone (VAD), VAD was superior particularly for relapsing myeloma (response rate of 60 vs. 23%). For VAD refractory myeloma, high-dose melphalan (HDM) programs were developed; total body irradiation (850 rad) followed by HDM 140 mg/m2 and supported by autologous bone marrow grafts was particularly effective and relatively well tolerated with all 4 patients still in remission from 3 to 15 months.
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PMID:Biology and therapy of multiple myeloma. 312 42

The transcription factor PEA1 (a homologue of AP1 and c-jun) is highly active in several fibroblast cell lines, compared to its low activity in a myeloma and an embryo-carcinoma (EC) cell line. Serum components are essential to attain these high levels of PEA1 activity in fibroblasts. This serum requirement is abrogated by transformation with the oncogenes c-Ha-ras, v-src and polyoma middle T (Py-MT) but not by immortalization with polyoma large T (Py-LT), v-myc, c-myc or SV40 large T (SV40T). Expression in myeloma cells of the same transforming oncogenes, as well as v-mos and c-fos, activates PEA1, whereas expression of the same immortalizing oncogenes and EIA does not. These results suggest that a common target for transforming oncogenes is PEA1. Serum components have no effect on PEA1 activity in the myeloma and EC cell lines. In contrast, retinoic acid treatment of F9 EC cells augments PEA1 activity. These results suggest that transforming oncogene expression compensates for the absence of cell type-specific factors which are required to activate PEA1. Activation of PEA1 may lead to altered transcription of a set of transformation-related genes.
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PMID:Transforming but not immortalizing oncogenes activate the transcription factor PEA1. 314 63

Structural alterations of the c-myc oncogene in human Burkitt's lymphoma and mouse plasmacytoma suggest that this oncogene is involved in several B cell neoplasms. The possibility of c-myc alterations in human myeloma has not been explored, probably because the low proliferative activity characteristic of this tumor impairs the propagation of representative cell lines for the performance of adequate cytogenetic studies. This report describes alterations in the c-myc locus with concomitant elevated expression of mRNA in the tumor cells of two of 37 patients with multiple myeloma. In one case, somatic cell hybrid studies revealed that the cloned rearranged DNA was entirely derived from chromosome 8, thus indicating a novel mechanism of c-myc activation different from that in Burkitt's lymphoma. Seven other patients exhibited five- to 12-fold overexpression of c-myc RNA when compared with normal marrow cells. Elevated mRNA expression in about one fourth of our patients suggests that the c-myc oncogene has a pathogenetic role in the evolution of multiple myeloma.
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PMID:Alteration and abnormal expression of the c-myc oncogene in human multiple myeloma. 327 75

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


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