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

Francesco Maura, Giovanna Cutrona, Laura Mosca, Serena Matis, Marta Lionetti, Sonia Fabris, Luca Agnelli, Monica Colombo, Carlotta Massucco, Manuela Ferracin, Barbara Zagatti, Daniele Reverberi, Massimo Gentile, Anna Grazia Recchia, Sabrina Bossio, Davide Rossi, Gianluca Gaidano, Stefano Molica, Agostino Cortelezzi, Francesco Di RaimondoMassimo Negrini, Pierfrancesco Tassone, Fortunato Morabito, Manlio Ferrarini, Antonino Neri

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3150-3158
Number of pages9
JournalLeukemia and Lymphoma
Volume56
Issue number11
DOIs
Publication statusPublished - Nov 2 2015

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Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

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, A. G., Bossio, S., Rossi, D., Gaidano, G., Molica, S., Cortelezzi, A., ... Neri, A. (2015). Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia. Leukemia and Lymphoma, 56(11), 3150-3158. https://doi.org/10.3109/10428194.2015.1028051