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)

Intracytoplasmic mu-positive pre-B cells (mu+VH315- cells) transformed with Abelson virus continuously produced cells (mu+VH315+ cells) that were double-stained by anti-mu and anti-VH315 antibodies which specifically recognized the immunoglobulin heavy chain variable region identical or closely related to that of MOPC315 myeloma protein. Southern blot analysis indicated that the mu+VH315+ cells were generated from the mu+VH315- cells by the VH315.D.JH2 to a germline JH3 joining on the non-productive VH315.D.JH2 allele, which resulted in the production of mu-chains with variable region detectable by anti-VH315 antibodies. Therefore, it is strongly indicated that VHDJH to JH joining is not blocked in mu-chain-producing pre-B cells, and thus is free from allelic exclusion machinery.
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PMID:VHDJH to JH joining is not blocked in mu-chain-producing pre-B cells, implying the breakdown of allelic exclusion. 212 42

To develop a molecular-based assay so that the diagnosis of feline B-cell neoplasia can be facilitated, we have characterized 24 feline immunoglobulin heavy chain variable region (IGH V) complementary DNA (cDNA) transcripts. Structural homology with rearranged human IGH V genes was found, and the sequence information was used to design a feline-specific polymerase chain reaction (PCR)-based assay to amplify the complementarity determining region 3 as a marker for B-cell clonality. Conserved primers derived from the second and third framework regions of V gene segments were used in conjunction with 2 sequence-specific primers and 1 degenerate primer derived from the J gene segments. Each PCR reaction was run in duplicate, and both native and denatured PCR products were evaluated using polyacrylamide gel electrophoresis. Formalin-fixed, paraffin-embedded (FFPE) tissue sections from cats with confirmed B-cell neoplasia (diffuse large B-cell lymphoma, plasmacytoma, and myeloma) were examined, and 15/22 (68.2%) cats produced results indicative of the presence of a monoclonal population of B cells. The evaluation of denatured PCR products (heteroduplex analysis) facilitated a more accurate interpretation in 3/15 (20%) cats. Pseudoclonality was a major reason for the failure to detect monoclonality. Poor DNA quality is a significant concern and was responsible for the removal of 2 cats from the study. Using this assay, FFPE normal feline lymphoid tissues and unfixed peripheral blood mononuclear cells were determined to be composed of polyclonal populations of B cells. This assay represents a useful adjunctive diagnostic tool for the diagnosis and investigation of feline B-cell lymphoproliferative disorders.
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PMID:Characterization of feline immunoglobulin heavy chain variable region genes for the molecular diagnosis of B-cell neoplasia. 1614 6

Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells (PCs) in the bone marrow (BM). MM is viewed as a clonal disorder due to lack of verified intraclonal sequence diversity in the immunoglobulin heavy chain variable region gene (IGHV). However, this conclusion is based on analysis of a very limited number of IGHV subclones and the methodology employed did not permit simultaneous analysis of the IGHV repertoire of non-malignant PCs in the same samples. Here we generated genomic DNA and cDNA libraries from purified MM BMPCs and performed massively parallel pyrosequencing to determine the frequency of cells expressing identical IGHV sequences. This method provided an unprecedented opportunity to interrogate the presence of clonally related MM cells and evaluate the IGHV repertoire of non-MM PCs. Within the MM sample, 37 IGHV genes were expressed, with 98.9% of all immunoglobulin sequences using the same IGHV gene as the MM clone and 83.0% exhibiting exact nucleotide sequence identity in the IGHV and heavy chain complementarity determining region 3 (HCDR3). Of interest, we observed in both genomic DNA and cDNA libraries 48 sets of identical sequences with single point mutations in the MM clonal IGHV or HCDR3 regions. These nucleotide changes were suggestive of putative subclones and therefore were subjected to detailed analysis to interpret: 1) their legitimacy as true subclones; and 2) their significance in the context of MM. Finally, we report for the first time the IGHV repertoire of normal human BMPCs and our data demonstrate the extent of IGHV repertoire diversity as well as the frequency of clonally-related normal BMPCs. This study demonstrates the power and potential weaknesses of in-depth sequencing as a tool to thoroughly investigate the phylogeny of malignant PCs in MM and the IGHV repertoire of normal BMPCs.
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PMID:Comprehensive assessment of potential multiple myeloma immunoglobulin heavy chain V-D-J intraclonal variation using massively parallel pyrosequencing. 2252 5

Myeloma develops due to the accumulation of multiple pathological genetic events, many of which have been defined. Hyperdiploidy and reciprocal translocations centered on the immunoglobulin heavy chain variable region constitute primary genetic lesions. These primary lesions co-operate with secondary genetic events including chromosomal deletions and gains, gene mutations and epigenetic modifiers such as DNA methylation to produce the malignant phenotype of myeloma. Some of these events have been linked with distinct clinical outcome and can be used to define patient groups. This review explores the molecular biology of myeloma and identifies how genetic lesions can be used to define high- and low-risk patient groups, and also defines potential targets for therapy. The authors also explore how this information can be used to guide therapeutic decision-making and the design and interpretation of clinical trials, both now and in the future.
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PMID:Understanding the molecular biology of myeloma and its therapeutic implications. 2321 92