Association between distinct gene and miRNA expression profiles and utilization of stereotyped subset #4 in the cells of CLL patients [Gene Expression]

Highly homologous B-cell receptors, stereotyped BCR, are expressed in a recurrent fraction of patients with chronic lymphocytic leukemia (CLL). In this study, we investigated the biological and molecular features of leukemic cells from 16 patients utilizing stereotyped subset #4 BCR (IGHV4-34) in a prospective cohort of 462 Binet stage A CLL patients. All subset #4 patients were characterized by the IGHV mutated gene configuration and by the absence of unfavorable cytogenetic lesions, and NOTCH1 and SF3B1 mutations. Gene expression profiling demonstrated a significant downregulation of WDFY4, MF2A and upregulation of PDGFA, FGFR1 and TFEC genes in leukemic cells from subset #4 compared to those from the remaining IGHV-mutated patients. Similarly, in the cells from subset #4 cases there was a specific miRNA expression pattern involving the upregulation of miR-497 and miR-29c. Furthermore transfection of miR-497 mimic in primary leukemic CLL cells induced a downregulation of BCL2, known to be a validated target of this miRNA. Our data identify a distinct gene and miRNA expression profile of the cells from subset #4 patients, providing further evidence for the putative role of BCR in shaping the features of the leukemic cells.

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Maura F, Cutrona G, Mosca L, Matis S, Lionetti M, Fabris S, Agnelli L, Colombo M, Massucco C, Ferracin M, Zagatti B, Reverberi D, Gentile M, Recchia AG, Bossio S, Rossi D, Gaidano G, Molica S, Cortelezzi A, Di Raimondo F, Negrini M, Tassone P, Morabito F, Ferrarini M, Neri A