TY - JOUR
T1 - Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia
AU - Maura, Francesco
AU - Cutrona, Giovanna
AU - Mosca, Laura
AU - Matis, Serena
AU - Lionetti, Marta
AU - Fabris, Sonia
AU - Agnelli, Luca
AU - Colombo, Monica
AU - Massucco, Carlotta
AU - Ferracin, Manuela
AU - Zagatti, Barbara
AU - Reverberi, Daniele
AU - Gentile, Massimo
AU - Recchia, Anna Grazia
AU - Bossio, Sabrina
AU - Rossi, Davide
AU - Gaidano, Gianluca
AU - Molica, Stefano
AU - Cortelezzi, Agostino
AU - Di Raimondo, Francesco
AU - Negrini, Massimo
AU - Tassone, Pierfrancesco
AU - Morabito, Fortunato
AU - Ferrarini, Manlio
AU - Neri, Antonino
N1 - Publisher Copyright:
© 2015 Informa UK, Ltd.
PY - 2015/11/2
Y1 - 2015/11/2
N2 - 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.
AB - 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.
KW - B-cell receptor
KW - BCL2
KW - chronic lymphocytic leukemia
KW - gene expression profiling
KW - microRNA
KW - stereotyped VH CDR
UR - http://www.scopus.com/inward/record.url?scp=84947813967&partnerID=8YFLogxK
U2 - 10.3109/10428194.2015.1028051
DO - 10.3109/10428194.2015.1028051
M3 - Article
SN - 1042-8194
VL - 56
SP - 3150
EP - 3158
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 11
ER -
