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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2989-2998.
Prepublished online as a Blood First Edition Paper on December 5, 2006; DOI 10.1182/blood-2006-10-051110.
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NEOPLASIA
Comprehensive characterization of IGHV3-21–expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study
Riccardo Bomben1,
Michele Dal Bo1,
Daniela Capello2,
Dania Benedetti1,
Daniela Marconi3,
Antonella Zucchetto1,
Francesco Forconi4,
Rossana Maffei5,
Emanuela M. Ghia6,
Luca Laurenti7,
Pietro Bulian1,
Maria Ilaria Del Principe8,
Giuseppe Palermo3,
Mia Thorsélius9,
Massimo Degan1,
Renato Campanini3,
Anna Guarini5,
Giovanni Del Poeta8,
Richard Rosenquist9,
Dimitar G. Efremov10,
Roberto Marasca5,
Robin Foà6,
Gianluca Gaidano2, and
Valter Gattei1
1 Clinical and Experimental Hematology Research Unit, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano (PN, Italy);
2 Division of Hematology, Department of Clinical and Experimental Medicine and Interdisciplinary Research Center on Autoimmune Diseases (IRCAD), Amedeo Avogadro University of Eastern Piedmont, Novara, Italy;
3 Department of Physics, University of Bologna, Italy;
4 Division of Hematology and Transplant, Department of Clinical Medicine and Immunological Sciences, University of Siena, Italy;
5 Division of Hematology, Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy;
6 Division of Hematology, Department of Cellular Biotechnologies and Hematology, University La Sapienza, Rome, Italy;
7 Hematology Institute, Catholic University Sacro Cuore, Rome, Italy;
8 Chair of Hematology, S Eugenio Hospital and University of Tor Vergata, Rome, Italy;
9 Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Sweden;
10 International Centre for Genetic Engineering and Biotechnology (ICGEB) Outstation-Monterotondo, Consiglio Nazionale delle Ricerche (CNR) Campus A. Buzzati-Traverso, Rome, Italy
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.
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