Comprehensive
characterization of IGHV3-21-expressing
B-cell chronic lymphocytic leukemia: an
Italian multicenter study.
Bomben R, Dal Bo M, Capello D, Benedetti
D, Marconi D, Zucchetto A, Forconi F,
Maffei R, Ghia EM, Laurenti L, Bulian P,
Del Principe MI, Palermo G, Thorsélius
M, Degan M, Campanini R, Guarini A, Del
Poeta G, Rosenquist R, Efremov DG,
Marasca R, Foŕ R, Gaidano G, Gattei V.
Clinical and
Experimental Hematology Research Unit,
Centro di Riferimento Oncologico, Istituto
di Ricovero e Cura a Carattere Scientifico (IRCCS),
Aviano PN, 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.
PMID: 17148579 [PubMed -
indexed for MEDLINE]