MicroRNA expression in tumor cells from Waldenstrom's macroglobulinemia reflects both their normal and malignant cell counterparts

Abstract

MicroRNAs (miRNAs) are involved in the regulation of many cellular processes including hematopoiesis, with the aberrant expression of differentiation-stage specific miRNA associated with lymphomagenesis. miRNA profiling has been essential for understanding the underlying biology of many hematological malignancies; however the miRNA signature of the diverse tumor clone associated with Waldenstrom's macroglobulinemia (WM), consisting of B lymphocytes, plasmacytes and lymphoplasmacytic cells, has not been characterized. We have investigated the expression of over 13 000 known and candidate miRNAs in both CD19 ⁺ and CD138 ⁺ WM tumor cells, as well as in their malignant and non-malignant counterparts. Although neither CD19 ⁺ nor CD138 ⁺ WM cells were defined by a distinct miRNA profile, the combination of all WM cells revealed a unique miRNA transcriptome characterized by the dysregulation of many miRNAs previously identified as crucial for normal B-cell lineage differentiation. Specifically, miRNA-9 ^*/152/182 were underexpressed in WM, whereas the expression of miRNA-21/125b/181a/193b/223/363 were notably increased (analysis of variance; P<0.0001). Future studies focusing on the effects of these dysregulated miRNAs will provide further insight into the mechanisms responsible for the pathogenesis of WM.