CD20+ Plasma Cell Myeloma (PCM): Molecular Characterization by miRNA Profiling Leads to New Insights into Disease Biology and Clinico-Pathological Behavior
Ravindra Kolhe, Amyn Rojiani, Anand Jillella, Vamsi Kota. Georgia Health Sciences University, Augusta, GA
Background: 15-20% of patients with PCM have strong expression of CD20, with unclear significance.
Profiling studies also found an association between cyclin D1, t(11;14) and CD20 expression with no prognostic significance. Recently, a class of noncoding RNAs called miRNAs was identified as critical gene regulators in development and class switch. Our study investigates the importance of these miRNAs in CD20+ PCM.
Design: miRNA expression profile of CD20+ PCM (n=6), diffuse large B cell lymphoma (DLBCL) (n=6), and CD20-ve PCM (n=8) were evaluated using the Affeymertrix miRNA microarray platform on GeneChip miRNA 2.0 array in FFPE samples. Following 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). Confirmation of the array data was done on the FirePlex Assay (Firefly BioWorks, Inc) platform which utilizes encoded hydrogel microparticles to perform multiplexed detection of microRNAs with readout on a standard flow cytometer.
Results: The miRNA expression profiles of CD20+ PCM, show significant (>4 times) upregulation of a set of 7 miRNAs, and downregulation of 8 miRNAs. miR-155, the miRNA upregulated in various B cell lymphomas, which plays a key role in the lymphomagenesis was amongst one of the miRNAs that were upregulated in our CD20+ PCM.
Conclusions: miR-155 represses 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 in the germinal centers upon antigen stimulation and hence plays a role in antibody class switching and plasma cell formation. We propose that this sustained 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.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 225, Wednesday Afternoon