Clonal plasma cell pathophysiology and clinical features of disease are linked to clonal plasma cell expression of cyclin D1 in systemic light-chain amyloidosis Journal Article

  

Authors:	Zhou, P.; Hoffman, J.; Landau, H.; Hassoun, H.; Iyer, L.; Comenzo, R. L.
Article Title:	Clonal plasma cell pathophysiology and clinical features of disease are linked to clonal plasma cell expression of cyclin D1 in systemic light-chain amyloidosis
Abstract:	Background: Overexpression of cyclin D1 (CCND1) in the clonal plasma cells (PCs) of patients with systemic light chain amyloidosis (AL) has been shown to occur even in cases without t(11;14). Associations between CCND1 expression and the clonal PC disease that underlies AL and the clinical features that characterize AL have not been systematically evaluated. Patients and Methods: To assess the significance of CCND1 expression in the pathophysiology of the clonal PC in AL, we evaluated CD138+ marrow PC from 16 newly diagnosed untreated patients by gene expression profiling (GEP) and performed a supervised analysis comparing clones that overexpressed CCND1 with those that did not. To assess the significance of CCND1 expression with respect to the clinical features of AL, we developed and validated a real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) method for quantitating expression of CCND1 in the CD138+ marrow PC cells from 53 newly diagnosed cases of AL. Results: In the analysis of GEP data, clones that overexpressed CCND1 also expressed significantly higher levels of endoplasmic reticulum protein processing genes such as SEL1L, Sec63, and PDIA6. In the analysis of RT-qPCR data, patients whose clones overexpressed CCND1 more often made only free light chains and fewer intact M-proteins, and also had a lower response rate to initial therapy. In multivariate analysis, CCND1 expression was an independent baseline predictor of survival in AL. Conclusion: CCND1 expression is a feature of the clonal PC disease in AL that merits prospective evaluation. © 2012 Elsevier Inc. All rights reserved.
Keywords:	survival; adult; controlled study; aged; major clinical study; overall survival; clinical feature; validation process; pathophysiology; quality control; reverse transcription polymerase chain reaction; gene expression profiling; amyloidosis; light chain; plasma cell; endoplasmic reticulum; quantitative analysis; protein secretion; multivariate analysis; real time polymerase chain reaction; cell clone; cyclin d1; m protein; immunoglobulin light chains; plasma cells; syndecan 1; protein quality; paraprotein; bnp
Journal Title:	Clinical Lymphoma, Myeloma and Leukemia
Volume:	12
Issue:	1
ISSN:	2152-2650
Publisher:	Elsevier Inc.
Date Published:	2012-02-01
Start Page:	49
End Page:	58
Language:	English
DOI:	10.1016/j.clml.2011.09.217
PROVIDER:	scopus
PUBMED:	22100494
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84856853155&partnerID=40&md5=d515c1dbf51e026aeb71cc5396319d98
Notes:	--- - "Export Date: 2 April 2012" - "Source: Scopus"

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