Plasmablastic Lymphoma (PBL): Molecular Characterization by miRNA Expression Profiling
Ravindra Kolhe, Amyn Rojiani, Anand Jillella, Vamsi Kota. Georgia Health Sciences University, Augusta, GA
Background: PBL is an aggressive B-cell lymphoma(DLBCL) that is likely to affect young HIV+ve men. Studies have suggested that tumors with PBL morphology represent a group of neoplasms corresponding to different entities including extramedullary plasmablastic tumors associated with plasma cell myeloma (PCM). Recently, a class of noncoding RNAs called miRNAs has emerged as critical gene regulators in cell growth, disease, and development. The goal of the current study was to evaluate the similarities and differences among PBL, DLBCL and PCM.
Design: The miRNA expression profile of PBL (n=6), PCM (n=13), and DLBCL (n=6), were evaluated using the Affeymertrix miRNA microarray platform on GeneChip miRNA 2.0 array in paraffin-embedded 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).The FirePlex Assay (Firefly BioWorks, Inc) was used to profile microRNAs in total RNA purified from the FFPE specimen. This platform utilizes encoded hydrogel microparticles to perform multiplexed detection of microRNAs with readout on a standard flow cytometer.
Results: The miRNA expression profiles of PBL vs DLBCL vs PCM, show significant (>10 times, p<0.05) upregulation of a set of 10 miRNAs, and down regulation of 5 miRNAs. Interestingly, miR-196a was upregulated 13X (p< 0.0047) as compared to DLBCL.
Conclusions: To the best of our knowledge, the current study represents the first global miRNA profiling of PBL. Recent studies have shown that miR-196a directly targets Annexin A1 (ANXA1) and represses its expression in cancers and promotes cell proliferation, anchorage-independent growth & suppresses apoptosis. miRNA-196a levels are inversely correlated with survival in pancreatic adenocarcinoma patients. miR-196a also plays a direct role in the down-regulation of keratin 5 (KRT5), small prolinerich protein 2C (SPRR2C), and S100 calcium-binding protein A9 (S100A9) genes whose expression is characteristically decreased or lost during neoplastic transformation. We propose that this sustained overexpression of miR-196a along with set of 14 deregulated miRNAs in PBL suppresses ANXA1 like activity, inducing cell proliferation and may explain some of the very aggressive behavior of PBL. This work is intriguing for the new information it provides about the complete set of deregulated mirna's and role of miR-196a in PBL.
Monday, March 4, 2013 2:00 PM
Proffered Papers: Section C, Monday Afternoon