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)

Plasma cell malignancy, multiple myeloma, is the prototype of monoclonal terminal-differentiated B cell proliferation that reveals a monoclonal Ig in the serum and/or urine of the majority of patients. New insights into the biology and pathogenesis of this entity are based on careful research to a complex cytokine network including TNF beta, IL-1 beta, and IL-6, many oncogene products such as bc1-2 protein, H-ras p-21 protein, and RB-1 product, and cell surface antigens associated with myeloma cells. The recent understanding on the mechanism for acquisition of IgV region diversity during B cell development has clarified the origin of the clonogenic cell in multiple myeloma. Further identification of new prognostic parameters as well as new therapeutic agents is necessary for the rational therapy of this refractory malignancy.
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PMID:[Advances in biology and pathogenesis of multiple myeloma]. 769 96

We looked for abnormalities of the retinoblastoma (RB-1) gene and of RB protein expression in 35 patients with multiple myeloma (MM). Mutations in exons 20 to 24 of the RB-1 gene (exons where mutations predominate in retinoblastoma and other solid tumors) were analyzed by single stranded conformation polymorphism (SSCP). RB-1 protein was studied in bone marrow plasma cells by immunocytochemistry (ABC peroxidase technique) with a specific monoclonal antibody. Southern blot analysis of RB-1 gene was also performed in 20 of the patients. Twenty two patients analyzed had advanced disease (stage III or, in one case, plasma cell leukemia) and cytogenetic analysis (performed in 31 cases) found monosomy 13 in 9 patients. No rearrangement of the RB-1 gene was found by Southern analysis. Absent or greatly reduced RB-1 protein level was found in plasma cells in 4 of the patients (11%), whereas normal levels were seen in the remaining cases. No point mutation in exons 20 to 24 and their flanking introns were found in any of the 35 patients. Three of the 4 patients with absent or reduced RB-1 protein expression had advanced MM (stage III: 2 cases; plasma cell leukemia: 1 case); all 4 patients were resistant to treatment (as compared to 7 of the 31 patients with normal RB-1 protein levels); only one of them was subsequently found to have monosomy 13 (as compared to 9 of the 28 other karyotyped patients). Our findings suggest that abnormalities of the RB-1 gene and its expression are rare in MM. Absent or reduced expression of RB-1 protein was not significantly correlated to monosomy 13 and was not associated with gross rearrangements of the RB-1 gene by Southern analysis or point mutations in exons 20 to 24 of the gene. Reduced expression of RB-1 protein may be associated with advanced disease and poor response to treatment, although larger numbers of patients will be required for more adequate conclusions.
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PMID:The retinoblastoma gene (RB-1) status in multiple myeloma: a report on 35 cases. 852 59

We have studied the retinoblastoma (RB-1) susceptibility gene status and pRB expression in 22 human myeloma cell lines (HMCL) and in 10 patients with advanced multiple myeloma (MM). Deletions of the RB-1 gene were observed in 81% (17/21) of the informative HMCL, regardless of their paracrine or autocrine interleukin-6 (IL-6) status. Among the deleted HMCL, only one (U266) had a biallelic deletion and lacked pRB expression. Monoallelic deletions had no consequence on the RB-1 gene activation and pRB expression. One patient of 10 presented the same biallclic deletion as U266 and six of 10 had monoallelic deletions. We conclude that monoallelic deletions of the RB-1 gene are frequent in HMCL and MM patients but have no consequence on gene activation and pRB expression.
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PMID:High incidence of deletions but infrequent inactivation of the retinoblastoma gene in human myeloma cells. 855 72

Genetic mechanisms leading to the development of multiple myeloma (MM) remain poorly understood. Given the frequency of chromosome 13 deletion in MM and the localization in 13q14 of the retinoblastoma susceptibility gene RB-1, an involvement of RB-1 in MM pathogenesis has been proposed. Moreover, interleukin-6 (IL-6) has been shown to be the main growth factor for MM in vitro and in vivo. The product of the RB-1 gene (pRB) can down-regulate IL-6 gene expression. Absence of pRB may then induce an autocrine IL-6 expression in myeloma cells and contribute to the autonomous growth of MM. As assessed in this review, heterozygous deletion of RB-1 is very common in MM but does not alter gene transcription and protein expression. Nevertheless, homozygous deletion of RB-1 has been identified in some MM patients with advanced disease and in the IL-6-autocrine human myeloma cell line U266. Thus, even if inactivation of RB-1 appears to be only a rare and late oncogenic event in MM and is not likely to represent the main mechanism involved in IL-6 up-regulation in MM, definitive assessment of the actual role played by RB-1 in MM pathogenesis still needs further investigation particularly the examination of pRB function.
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PMID:The retinoblastoma susceptibility gene RB-1 in multiple myeloma. 915 53

In this study we evaluated the replication pattern and cell-cycle dynamics of cells from patients considered to have a premalignant condition (monoclonal gammopathy, or MGUS) and patients with multiple myeloma (MM), as well as healthy controls. We applied the fluorescence in situ hybridization (FISH) technique with the TP53, RB-1 and 21q22 loci on the patient's cells. Asynchrony was determined by the presence of one single and one set of double dots in the same cell. The rate of asynchronic replication was significantly higher in the cells from MM patients, with intermediate value in the cells from MGUS, while the lowest rate was in cells from controls. We suggest that these results may reflect the changes in gene replication and cell-cycle progression that occur in premalignant and malignant cells.
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PMID:Replication pattern in cancer: asynchronous replication in multiple myeloma and in monoclonal gammopathy. 997 21

Deletions of 13q14.3 are well known in several malignancies and are thought to be associated with tumour suppressor function. The RB-1 gene is a tumour suppressor gene, but other loci including D13S319 and D13S25 telomeric to this within 13q14.3 are deleted in B-cell chronic lymphocytic leukaemia (B-CLL), multiple myeloma and non-Hodgkin's lymphoma, with varying clinical significance. The fluorescence in situ hybridization screening of 22 patients with T-prolymphocytic leukaemia (T-PLL) for deletions of 13q14.3 revealed loss of D13S25 in 17 cases (mean 40% range 13-98%), with 11 patients having at least a 20% deletion. Mapping the deletions for the RB-1, D13S319,and D13S25 loci revealed D13S25 as the most frequently deleted marker. However, patients with only the D13S25 deletion had low percentages of cells with the deletion (12-13%), suggesting that loss of D13S25 on its own may not provide sufficient growth advantage. The use of the YAC 954c12, which maps immediately adjacent to D13S25, defined the telomeric border of the deletion in some of the cases. Inv(14)(q11q32) and t(14;14)(q11;q32) are characteristic of T-PLL, but are also observed in premalignant T-cell clones in patients with ataxia telangiectasia. Transition to overt leukaemia may result from loss of suppressor function. Thus, 13q14.3 deletions could contribute to the development of overt leukaemia in T-PLL, but the involvement of more than one gene in the region cannot be excluded.
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PMID:Deletions of D13S25, D13S319 and RB-1 mapping to 13q14.3 in T-cell prolymphocytic leukaemia. 1152 51

Multiple myeloma (MM) is a malignancy of differentiated B lymphocytes and has remained an incurable disease. Chromosomal abnormalities are among the most important prognostic parameters for MM. Cytoplasm immunoglobulin-enhanced interphase fluorescent in situ hybridization (FISH) has been a standard cell-targeting method for identifying genomic aberrations in MM. We have developed another cell-targeting approach by using CD138 magnetic microbeads to sort plasma cells for FISH analysis. The FISH panel consisted of four probes targeting RB-1, D13S319, immunoglobulin H, and p53 loci. We reviewed the FISH and conventional cytogenetic results of 60 patients with MM. The present cell-targeting approach in conjunction with the FISH probe panel was more sensitive than FISH performed on untargeted cells in detecting prognostically significant genomic aberrations (72 versus 24%, P = 0.0016). The frequencies of genomic abnormalities identified were similar to previously reported data obtained with the standard cell-targeting method. Therefore, our cell-targeting approach and FISH panel reliably detect prognostically important genomic abnormalities in MM and are potentially suitable for widespread use.
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PMID:A practical approach to the detection of prognostically significant genomic aberrations in multiple myeloma. 1625 53

Multiple myeloma (MM) is a neoplasm of a terminally differentiated B-cell. Human myeloma cell lines were shown to be suitable model systems for use in various fields of the biological sciences. This study was aimed to investigate the genetic aberrations in human multiple myeloma cell lines. Interphase fluorescence in situ hybridization (FISH) with probes for the regions containing 13q14 (RB-1), 13q14.3 (D13S19), 14q32 (IGHC/IGHV) , 1q12 (CEP1), 17p13 (TP53) were was used to detect 7 HMCL and 85 cases of newly diagnosed MM. FISH with LSI IGH/CCND1 , LSI IGH/FGFR3 and LSI IGH/MAF probes were used to detect t(11;14) (q13;q32) , t(4;14) (p16;q32) and t(14;16) (q32;q23) in HMCL and MM with 14q32 rearrangement. The results showed that molecular cytogenetic aberrations were found in all 7 HMCL, six (85.7%) HMCL simultaneously had 13q14, 13q14.3 deletion. Chromosome 1q21 abnormality was found in six (33.3%) HMCL with at least 3 copies amplifications. Illegitimate 14q32 rearrangement was found in five (71.4%) HMCL, including one with t(11;14), two with t(4;14) and three with t(14;16). 17p13 deletion was detected in 5 HMCL. Chromosomal changes were observed in 85.9% of the 85 cases of newly diagnosed MM. The del(13), 1q12 amplification, del(17p), 14q32 rearrangement, t(11;14), t(4;14), t(14;16) were present in 44.7%, 52.9%, 20%, 62.4%, 27.1%, 24.7% and 3.5% of the patients respectively. There was no significant difference in the prevalence of genetic abnormalities of del(13q), 14q32 rearrangement, 1q12 amplification, t(11;14), t(4;14) except del(17p) and t(14;16). It is concluded that HMCL representative of the most aggressive phase of plasma cell neoplasms accumulated a large amount of genetic aberrations. Loss of p53 are strikingly common in HMCL suggesting that the impairment of the P53 tumor suppressor pathway is an important contributor to extramedullary tumor expansion.
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PMID:[Comparative study of genetic aberrations in human multiple myeloma cell lines and newly diagnosed MM by fluorescence in situ hybridization]. 2117 60

This study was to aimed investigate the influence of immunomagnetic sorting on detecting the genetic aberrations of multiple myeloma (MM) by interphase fluorescence in situ hybridization (FISH) and to explore the detection method suitable to use in our country. The genetic aberrations of immunomagnetically sorted and unsorted bone marrow cells from the same MM patients were detected by interphase FISH and the detectable rate of genetic aberration was compared. The types of probes included 13 q14 (RB-1) and 14q32 (IGH). The 42 and 22 sorted and unsorted marrow samples from MM patients were detected by using 13q14 probe and 14q32 probes respectively, the results indicated that the 13q14 deletion was found in 9 of 42 (21.4%) unsorted marrow samples and in 25 of 42 (56.8%) CD138(+)-sorted marrow samples. The 13q32 rearrangement was found in 7 of 22 (31.8%) unsorted marrow samples and in 14 of 22(63.6%) CD138(+)-sorted marrow samples. Both of the difference was statistically significant (p = 0.001 and p = 0.035 respectively). Percentages of cytogenetic alterations detected in unsorted bone marrow cells correlated positively with percentage of plasma cells tested by bone marrow smears or flow cytometry. When percentage of plasma cells tested by bone marrow smears exceed 50%, or by flow cytometry exceed 10%, there was no difference between 2 methods. It is concluded that immunomagnetic sorting of CD138(+) cells increases the probability of detection of the 13q14 deletion and 14q32 rearrangement in bone marrow samples. The low detectable rate of genetic aberration in unsorted bone marrow cells is associated to the low percentage of plasma cells in bone marrow samples, higher percentage of plasma cells can partly overcome the shortage of unsorted detection method. When percentage of plasma cells tested by bone marrow smears exceed 50%, or by flow cytometry exceed 10%, there was no difference between 2 methods.
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PMID:[Influence of immunomagnetic sorting on detecting genetic aberration of multiple myeloma cells by interphase fluorescence in situ hybridization]. 2136 21