Date of this Version
BLOOD, 24 May 2012 Volume 119, Number 21; doi 10.1182/blood-2011-07-370122
miRNA deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1–positive MCL (n = 30) and cyclin D1–negative MCL (n =7) and compared them with small lymphocytic leukemia/ lymphoma (n =12), aggressive B-cell lymphomas (n =138), normal B-cell subsets, and stromal cells.We identified a 19-miRNA classifier that included 6 up-regulated miRNAs and 13 down regulated miRNA that was able to distinguish MCL from other aggressive lymphomas. Some of the up-regulated miRNAs are highly expressed in naive B cells. This miRNAclassifier showed consistent results in formalinfixed paraffin-embedded tissues and was able to distinguish cyclin D1–negative MCL from other lymphomas. A 26-miRNA classifier could distinguish MCL from small lymphocytic leukemia/lymphoma, dominated by 23 up-regulated miRNAs in MCL. Unsupervised hierarchical clustering of MCL patients demonstrated a cluster characterized by high expression of miRNAs from the polycistronic miR17-92 cluster and its paralogs, miR-106a-363 and miR-106b-25, and associated with high proliferation gene signature. The other clusters showed enrichment of stroma-associated miRNAs, and also had higher expression of stroma-associated genes. Our clinical outcome analysis in the present study suggested that miRNAs can serve as prognosticators.