title: Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia.
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.
authors: a Department of Clinical Sciences and Community Health , University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milano , Italy.
authors: Francesco
authors: F
authors: Maura
authors: b SS Molecular Diagnostics, IRCCS S. Martino-IST , Genova , Italy.
authors: Giovanna
authors: G
authors: Cutrona
authors: a Department of Clinical Sciences and Community Health , University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milano , Italy.
authors: Laura
authors: L
authors: Mosca
authors: c Scientific Direction IRCCS S. Martino-IST , Genova , Italy.
authors: Serena
authors: S
authors: Matis
authors: a Department of Clinical Sciences and Community Health , University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milano , Italy.
authors: Marta
authors: M
authors: Lionetti
authors: a Department of Clinical Sciences and Community Health , University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milano , Italy.
authors: Sonia
authors: S
authors: Fabris
authors: a Department of Clinical Sciences and Community Health , University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milano , Italy.
authors: Luca
authors: L
authors: Agnelli
authors: c Scientific Direction IRCCS S. Martino-IST , Genova , Italy.
authors: Monica
authors: M
authors: Colombo
authors: c Scientific Direction IRCCS S. Martino-IST , Genova , Italy.
authors: Carlotta
authors: C
authors: Massucco
authors: d Department of Morphology , Surgery and Experimental Medicine and Laboratory for the Technologies of Advanced Therapies (LTTA), University of Ferrara , Genova , Italy.
authors: Manuela
authors: M
authors: Ferracin
authors: d Department of Morphology , Surgery and Experimental Medicine and Laboratory for the Technologies of Advanced Therapies (LTTA), University of Ferrara , Genova , Italy.
authors: Barbara
authors: B
authors: Zagatti
authors: e Department of Pathology IRCCS S. Martino-IST , Genova , Italy.
authors: Daniele
authors: D
authors: Reverberi
authors: f U.O.C. di Ematologia, Azienda Ospedaliera di Cosenza , Cosenza , Italy.
authors: Massimo
authors: M
authors: Gentile
authors: f U.O.C. di Ematologia, Azienda Ospedaliera di Cosenza , Cosenza , Italy.
authors: Anna Grazia
authors: AG
authors: Recchia
authors: f U.O.C. di Ematologia, Azienda Ospedaliera di Cosenza , Cosenza , Italy.
authors: Sabrina
authors: S
authors: Bossio
authors: g Division of Hematology, Department of Translational Medicine , Amedeo Avogadro University of Eastern Piedmont , Novara , Italy.
authors: Davide
authors: D
authors: Rossi
authors: g Division of Hematology, Department of Translational Medicine , Amedeo Avogadro University of Eastern Piedmont , Novara , Italy.
authors: Gianluca
authors: G
authors: Gaidano
authors: h Department of Oncology and Hematology , Pugliese-Ciaccio Hospital , Catanzaro , Italy.
authors: Stefano
authors: S
authors: Molica
authors: a Department of Clinical Sciences and Community Health , University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milano , Italy.
authors: Agostino
authors: A
authors: Cortelezzi
authors: i University of Catania and Ferrarotto Hospital, Catania, Department of Biomedical Sciences , Division of Hematology , Catanzaro , Italy.
authors: Francesco
authors: F
authors: Di Raimondo
authors: d Department of Morphology , Surgery and Experimental Medicine and Laboratory for the Technologies of Advanced Therapies (LTTA), University of Ferrara , Genova , Italy.
authors: Massimo
authors: M
authors: Negrini
authors: j Department of Experimental and Clinical Medicine , Magna Graecia University , Catanzaro , Italy.
authors: Pierfrancesco
authors: P
authors: Tassone
authors: f U.O.C. di Ematologia, Azienda Ospedaliera di Cosenza , Cosenza , Italy.
authors: Fortunato
authors: F
authors: Morabito
authors: c Scientific Direction IRCCS S. Martino-IST , Genova , Italy.
authors: Manlio
authors: M
authors: Ferrarini
authors: a Department of Clinical Sciences and Community Health , University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milano , Italy.
authors: Antonino
authors: A
authors: Neri
mesh_terms: D000368:Aged; D016175:B-Lymphocyte Subsets / Q000378:metabolism; D016000:Cluster Analysis; D022801:Complementarity Determining Regions / Q000235:genetics; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1 / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics; D059467:Transcriptome
chemical_list: D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D035683:MicroRNAs; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1; D011947:Receptors, Antigen, B-Cell; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human
keywords: B-cell receptor; BCL2; chronic lymphocytic leukemia; gene expression profiling; microRNA; stereotyped VH CDR