title: Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study.
abstract: IGHV3-21-using chronic lymphocytic leukemia (CLL) is a distinct entity with restricted immunoglobulin gene features and poor prognosis and is more frequently encountered in Northern than Southern Europe. To further investigate this subset and its geographic distribution in the context of a country (Italy) with both continental and Mediterranean areas, 37 IGHV3-21 CLLs were collected out of 1076 cases enrolled by different institutions from Northern or Central Southern Italy. Of the 37 cases, 18 were identified as homologous (hom)HCDR3-IGHV3-21 CLLs and were found almost exclusively (16 of 18) in Northern Italy; in contrast, 19 nonhomHCDR3-IGHV3-21 cases were evenly distributed throughout Italy. Clinically, poor survivals were documented for IGHV3-21 CLLs as well as for subgroups of mutated and homHCDR3-IGHV3-21 CLLs. Negative prognosticators CD38, ZAP-70, CD49d, and CD79b were expressed at higher levels in homHCDR3 than nonhomHCDR3-IGHV3-21 cases. Differential gene expression profiling (GEP) of 13 IGHV3-21 versus 52 non-IGHV3-21 CLLs identified, among 122 best-correlated genes, TGFB2 and VIPR1 as down- and up-regulated in IGHV3-21 CLL cases, respectively. Moreover, GEP of 7 homHCDR3 versus 6 nonhomHCDR3-IGHV3-21 CLLs yielded 20 differentially expressed genes, with WNT-16 being that expressed at the highest levels in homHCDR3-IGHV3-21 CLLs. Altogether, IGHV3-21 CLLs, including those with homHCDR3, had a peculiar global phenotype in part explaining their worse clinical outcome.
authors.affiliation: Clinical and Experimental Hematology Research Unit, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano PN, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bomben
authors.forename: Michele
authors.initials: M
authors.lastname: Dal Bo
authors.forename: Daniela
authors.initials: D
authors.lastname: Capello
authors.forename: Dania
authors.initials: D
authors.lastname: Benedetti
authors.forename: Daniela
authors.initials: D
authors.lastname: Marconi
authors.forename: Antonella
authors.initials: A
authors.lastname: Zucchetto
authors.forename: Francesco
authors.initials: F
authors.lastname: Forconi
authors.forename: Rossana
authors.initials: R
authors.lastname: Maffei
authors.forename: Emanuela M
authors.initials: EM
authors.lastname: Ghia
authors.forename: Luca
authors.initials: L
authors.lastname: Laurenti
authors.forename: Pietro
authors.initials: P
authors.lastname: Bulian
authors.forename: Maria Ilaria
authors.initials: MI
authors.lastname: Del Principe
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palermo
authors.forename: Mia
authors.initials: M
authors.lastname: Thorsélius
authors.forename: Massimo
authors.initials: M
authors.lastname: Degan
authors.forename: Renato
authors.initials: R
authors.lastname: Campanini
authors.forename: Anna
authors.initials: A
authors.lastname: Guarini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Del Poeta
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
authors.forename: Dimitar G
authors.initials: DG
authors.lastname: Efremov
authors.forename: Roberto
authors.initials: R
authors.lastname: Marasca
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Valter
authors.initials: V
authors.lastname: Gattei
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D050438:Genes, Immunoglobulin Heavy Chain; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007558:Italy / Q000453:epidemiology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011379:Prognosis; D017386:Sequence Homology, Amino Acid; D015996:Survival Rate
chemical_list: D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region