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

被引:21
作者
Maura, Francesco [1 ,2 ]
Cutrona, Giovanna [3 ]
Mosca, Laura [1 ,2 ]
Matis, Serena [4 ]
Lionetti, Marta [1 ,2 ]
Fabris, Sonia [1 ,2 ]
Agnelli, Luca [1 ,2 ]
Colombo, Monica [4 ]
Massucco, Carlotta [4 ]
Ferracin, Manuela [5 ,6 ]
Zagatti, Barbara [5 ,6 ]
Reverberi, Daniele [7 ]
Gentile, Massimo [8 ]
Recchia, Anna Grazia [8 ]
Bossio, Sabrina [8 ]
Rossi, Davide [9 ]
Gaidano, Gianluca [9 ]
Molica, Stefano [10 ]
Cortelezzi, Agostino [1 ,2 ]
Di Raimondo, Francesco [11 ,12 ]
Negrini, Massimo [5 ,6 ]
Tassone, Pierfrancesco [13 ]
Morabito, Fortunato [8 ]
Ferrarini, Manlio [4 ]
Neri, Antonino [1 ,2 ]
机构
[1] Univ Milan, Dept Clin Sci & Community Hlth, I-20122 Milan, Italy
[2] Fdn IRCCS Ca Granda, Osped Maggiore Policlin, Hematol CTMO 1, Milan, Italy
[3] IRCCS S Martino IST, SS Mol Diagnost, Genoa, Italy
[4] IRCCS S Martino IST, Sci Direct, Genoa, Italy
[5] Univ Ferrara, Dept Morphol Surg & Expt Med, I-44100 Ferrara, Italy
[6] Univ Ferrara, Lab Technol Adv Therapies LTTA, I-44100 Ferrara, Italy
[7] IRCCS S Martino IST, Dept Pathol, Genoa, Italy
[8] Azienda Osped Cosenza, UOC Ematol, Cosenza, Italy
[9] Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, Novara, Italy
[10] Pugliese Ciaccio Hosp, Dept Hematol & Oncol, Catanzaro, Italy
[11] Catania Univ, Catania, Italy
[12] Ferrarotto Hosp, Dept Biomed Sci, Div Hematol, Catania, Italy
[13] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Catanzaro, Italy
关键词
B-cell receptor; BCL2; chronic lymphocytic leukemia; gene expression profiling; microRNA; stereotyped VH CDR; CLINICAL-FEATURES; PROGRESSION; MUTATIONS; CANCER; IMMUNOGLOBULINS; MULTICENTER; GUIDELINES; DIAGNOSIS; APOPTOSIS; PATTERNS;
D O I
10.3109/10428194.2015.1028051
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:3150 / 3158
页数:9
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