MiRNA expression profiling of CD20+ plasma cell myeloma (PCM): Upregulation of miR-155 shedding new insight into disease biology and clinicopathologic behavior.

Abstract

8108 Background: Up to15-20% of patients with PCM have expression of CD20, although the significance of this remains unclear. The prognostic significance of CD20 expression in PCM is unclear. Recently, a class of noncoding RNAs, miRNAs, were identified as critical gene regulators in cell growth, disease, and development. Our study investigates importance of miRNAs in cases of CD20+ PCM and correlates them with clinicopathological parameters. Methods: The miRNA expression profile of CD20+ PCM (n=6), diffuse large B cell lymphoma (DLBCL) (n=6), and CD20 negative PCM (n=8) were evaluated using the Affeymertrix miRNA microarray platform on GeneChip miRNA 2.0 array in paraffin-embedded samples. After hybridization and data acquisition, we used Partek Genomics Suite software for RMA normalization and to determine statistically significant differences in miRNA expression between experimental groups by ANOVA and pairwise comparisons (two-sided α=0.05). Results: miRNA expression profiles of CD20+ PCM, show upto >4 times upregulation of 7 miRNAs and downregulation of 8 miRNAs. miR-155, the miRNA upregulated in various B cell lymphomas and plays a key role in the lymphomagenesis, was amongst the highest miRNAs that were upregulated. Conclusions: miR-155 is known to repress SH2-domain containing inositol-5-phosphatase-1 (SHIP-1), which is a critical phosphatase that negatively down modulates AKT pathway and has functions during normal B-cell development. Physiologically, miR-155 is upregulated during B-cell activation upon antigen stimulation and so plays a role in antibody class switching and plasma cell formation. We propose that this overexpression of miR-155 in CD20+ PCM unblocks AKT activity, inducing cell proliferation and may explain some of the immunophenotypic behavior of CD20+ PCM. This work is intriguing for the new information it provides about the role of miR-155 in CD20+ PCM. Furthermore, the phenotype of miR-155+ve CD20+ PCM might ultimately provide new insights into regulation of poorly understood steps in B cell differentiation and maturation into plasma cell and more importantly the clinicopathological behavior of this entity.