Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia

Abstract

In this study we investigated specific biological and clinical features associated with chronic lymphocytic leukemia (CLL) patients carrying stereotyped BCR subset #4 (IGHV4–34) among a prospective cohort of 462 CLL/MBL patients in early stage (Binet A). All subset #4 patients (n = 16) were characterized by the IGHV mutated gene configuration, and absence of unfavorable cytogenetic lesions, NOTCH1 or SF3B1 mutations. Gene and miRNA expression profiling evidenced that the leukemic cells of subset #4 cases showed significant downregulation of WDFY4, MF2A and upregulation of PDGFA, FGFR1 and TFEC gene transcripts, as well as the upregulation of miR-497 and miR-29c. The transfection of miR-497 mimic in primary leukemic CLL cells induced a downregulation of BCL2, a known validated target of this miRNA. Our data identify biological characteristics associated with subset #4 patients, providing further evidence for the putative role of BCR in shaping the features of the tumor cells in CLL.

Keywords::

• B-cell receptor
• BCL2
• chronic lymphocytic leukemia
• gene expression profiling
• microRNA
• stereotyped VH CDR

Acknowledgements

This work was supported by Associazione Italiana Ricerca sul Cancro (AIRC, AN-IG10136, MF IG14326, and FM-RG6432), AIRC–Special Program Molecular Clinical Oncology (5 per Mille, grant 9980, 2010-15; A.N., M.F., P.T., M.N. and F.Mo.) Ricerca Finalizzata from the Italian Ministry of Health 2006 (G.C., F.Mo., M.F., and P.T.) and 2007 (G.C.), Fondo Investimento per la Ricerca di Base (grant RBIP06LCA9; M.F.), progetto Compagnia San Paolo (G.C.), the Ministero della Salute, Ricerca Corrente, and Ricerca Finalizzata FSN, Rome, Italy (A.P.). S.B. and L.D.S. were supported by fellowships from the AIRC; M.L. was supported by a fellowship from the Fondazione Italiana Ricerca sul Cancro (FIRC).

Potential conflict of interest:

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Supplementary material available online

Supplementary Methods and materials

Supplementary Tables I–IV

Supplementary Figures 1–4. available online at http://informahealthcare.com/doi/abs/10.3109/10428194.2015.1028051.