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)

Serial analysis of gene expression (SAGE) allows a comprehensive profiling of gene expression within a given tissue and also an assessment of transcript abundance. We generated SAGE libraries from normal and neoplastic plasma cells to identify genes differentially expressed in multiple myeloma (MM). Normal plasma cells were obtained from palatine tonsils and MM SAGE library was generated from bone marrow plasma cells of MM patients. We obtained 29,918 SAGE tags from normal and 10,340 tags from tumor libraries. Computer-generated genomic analysis identified 46 upregulated genes in the MM library. Ten upregulated genes were selected for further investigation. Differential expression was validated by quantitative real-time PCR in purified plasma cells of 31 patients and three controls. P53CSV, DDX5, MAPKAPK2 and RANBP2 were found to be upregulated in at least 50% of the MM cases tested. All of them were also found upregulated in MM when compared to normal plasma cells in a meta-analysis using ONCOMINE microarray database. Antibodies specific to DDX5, RANBP2 and MAPKAPK2 were used in a TMA containing 57 MM cases and confirmed the expression of these proteins in 74%, 96%, and 21% of the MM samples, respectively. Analysis of differential expression using SAGE could identify genes important for myeloma tumorigenesis (P53CSV, DDX5, MAPKPK2 and RANBP2) and that could potentially be useful as therapeutic targets.
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PMID:SAGE analysis highlights the importance of p53csv, ddx5, mapkapk2 and ranbp2 to multiple myeloma tumorigenesis. 1917 22

Among the blood cancers, 13% mortality is caused by Multiple myeloma (MM) type of hematological malignancy. In spite of therapeutic advances in chemotherapy treatment, still MM remains an incurable disease is mainly due to emergence of chemoresistance. At present time, FDA approved bortezomib is the first line drug for MM treatment. However, like other chemotherapy, MM patients are acquiring resistance against bortezomib. The present study aims to identify and validate bortezomib resistant protein targets in MM using iTRAQ and label free quantitative proteomic approaches. 112 differentially expressed proteins were commonly found in both approaches with similar differential expression pattern. Exportin-1 (XPO1) protein was selected for further validation as its significant high expression was observed in both iTRAQ and label free analysis. Bioinformatic analysis of these common differentially expressed proteins showed a clear cluster of proteins such as SMC1A, RCC2, CSE1, NUP88, NUP50, TPR, HSPA14, DYNLL1, RAD21 and RANBP2 being associated with XPO1. Functional studies like cell count assay, flow cytometry assay and soft agar assay proved that XPO1 knock down in RPMI 8226R cell line results in re-sensitization to bortezomib drug. The mass spectrometry data are available via ProteomeXchange with identifier PXD013859. BIOLOGICAL SIGNIFICANCE: Multiple myeloma (MM) is a type of hematological malignancy which constitutes about 13% of all blood cell related malignancies. Chemoresistance is one of the major obstacles for the successful treatment for MM. Bortezomib is a first proteasome inhibitor drug, widely used in MM treatment. The present study aims to identify and validate bortezomib resistant protein targets in MM. Here, we identified 112 candidate proteins to be associated with bortezomib resistance using global quantitative proteomic analysis. Among these candidate proteins, we show that XPO1 plays crucial role in emerging bortezomib resistance using functional studies like cell count assay, flow cytometry assay and soft agar assay. XPO1 could be a potential therapeutic target for MM and development of inhibitors of XPO1 might help to cure MM.
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PMID:XPO1 is a critical player for bortezomib resistance in multiple myeloma: A quantitative proteomic approach. 3146 61