Genome-wide miRNA profiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis |
| |
Authors: | Iqbal Javeed Shen Yulei Liu Yanyan Fu Kai Jaffe Elaine S Liu Cuiling Liu Zhongfeng Lachel Cynthia M Deffenbacher Karen Greiner Timothy C Vose Julie M Bhagavathi Sharathkumar Staudt Louis M Rimsza Lisa Rosenwald Andreas Ott German Delabie Jan Campo Elias Braziel Rita M Cook James R Tubbs Raymond R Gascoyne Randy D Armitage James O Weisenburger Dennis D McKeithan Timothy W Chan Wing C |
| |
Affiliation: | Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA. |
| |
Abstract: | 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 miRNA classifier showed consistent results in formalin-fixed 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|