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

Ping Zhou, James Hoffman, Heather Landau, Hani Hassoun, Lakshmanan Iyer, Raymond L. Comenzo

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)49-58
Number of pages10
JournalClinical Lymphoma, Myeloma and Leukemia
Volume12
Issue number1
DOIs
StatePublished - Feb 2012
Externally publishedYes

Keywords

  • Amyloidosis
  • BNP
  • Cyclin D1
  • Immunoglobulin light chains
  • Plasma cells

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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