TY - JOUR
T1 - Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia
T2 - An Italian multicenter study
AU - Bomben, Riccardo
AU - Dal Bo, Michele
AU - Capello, Daniela
AU - Benedetti, Dania
AU - Marconi, Daniela
AU - Zucchetto, Antonella
AU - Forconi, Francesco
AU - Maffei, Rossana
AU - Ghia, Emanuela M.
AU - Laurenti, Luca
AU - Bulian, Pietro
AU - Del Principe, Maria Ilaria
AU - Palermo, Giuseppe
AU - Thorsélius, Mia
AU - Degan, Massimo
AU - Campanini, Renato
AU - Guarini, Anna
AU - Del Poeta, Giovanni
AU - Rosenquist, Richard
AU - Efremov, Dimitar G.
AU - Marasca, Roberto
AU - Foà, Robin
AU - Gaidano, Gianluca
AU - Gattei, Valter
PY - 2007/4/1
Y1 - 2007/4/1
N2 - 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,among122 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.
AB - 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,among122 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.
UR - http://www.scopus.com/inward/record.url?scp=33947598891&partnerID=8YFLogxK
U2 - 10.1182/blood-2006-10-051110
DO - 10.1182/blood-2006-10-051110
M3 - Article
SN - 0006-4971
VL - 109
SP - 2989
EP - 2998
JO - Blood
JF - Blood
IS - 7
ER -