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