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

• Published in: Leukemia & lymphoma Vol. 56; no. 11; pp. 3150 - 3158
• Main Authors: Maura, Francesco, Cutrona, Giovanna, Mosca, Laura, Matis, Serena, Lionetti, Marta, Fabris, Sonia, Agnelli, Luca, Colombo, Monica, Massucco, Carlotta, Ferracin, Manuela, Zagatti, Barbara, Reverberi, Daniele, Gentile, Massimo, Recchia, Anna Grazia, Bossio, Sabrina, Rossi, Davide, Gaidano, Gianluca, Molica, Stefano, Cortelezzi, Agostino, Di Raimondo, Francesco, Negrini, Massimo, Tassone, Pierfrancesco, Morabito, Fortunato, Ferrarini, Manlio, Neri, Antonino
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 02.11.2015
• Subjects: Aged; B-cell receptor; B-Lymphocyte Subsets - metabolism; BCL2; chronic lymphocytic leukemia; Cluster Analysis; Complementarity Determining Regions - genetics; Computational Biology; Female; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Variable Region - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Male; microRNA; MicroRNAs - genetics; Middle Aged; Mutation; Phosphoproteins - genetics; Receptor, Notch1 - genetics; Receptors, Antigen, B-Cell - genetics; Receptors, Antigen, B-Cell - metabolism; Reproducibility of Results; Ribonucleoprotein, U2 Small Nuclear - genetics; RNA Splicing Factors; stereotyped VH CDR; Transcriptome; BCL2; microRNA; chronic lymphocytic leukemia; B-cell receptor; gene expression profiling; stereotyped VH CDR
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428194.2015.1028051

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.