TY - JOUR
T1 - CD38 gene polymorphism and chronic lymphocytic leukemia
T2 - A role in transformation to Richter syndrome?
AU - Aydin, Semra
AU - Rossi, Davide
AU - Bergui, Luciana
AU - D'Arena, Giovanni
AU - Ferrero, Enza
AU - Bonello, Lisa
AU - Omedé, Paola
AU - Novero, Domenico
AU - Morabito, Fortunato
AU - Carbone, Antonino
AU - Gaidano, Gianluca
AU - Malavasi, Fabio
AU - Deaglio, Silvia
PY - 2008/6/15
Y1 - 2008/6/15
N2 - CD38 rules proliferation signals in chronic lymphocytic leukemia (CLL) cells, suggesting that the molecule is not merely a prognostic marker but also a key element in the pathogenetic network underlying the disease. CD38 has a genetic polymorphism, characterized by a C>G variation in the regulatory region of intron 1. The working hypothesis is that the presence of different alleles in CLL patients marks (or accounts for) some of the clinical heterogeneity. CD38 allele distribution in 248 Italian patients overlapped with that of the controls (n = 232), suggesting that susceptibility to CLL is not influenced by CD38 genotype. Stratification of patients according to markers of unfavorable prognosis constantly resulted in a significantly higher frequency of the rare G allele. Furthermore, analysis of clinical parameters showed that G allele is independently associated with nodal/splenic involvement. The highest G allele frequency was observed in the 16 patients of the cohort that developed Richter syndrome (RS). Five-year cumulative incidence of transformation was significantly higher in G allele carriers than in CC homozygotes. Multivariate analysis on a total of 30 RS patients confirmed that the probability of transformation is strongly associated with G allele, likely representing an independent risk factor for RS development.
AB - CD38 rules proliferation signals in chronic lymphocytic leukemia (CLL) cells, suggesting that the molecule is not merely a prognostic marker but also a key element in the pathogenetic network underlying the disease. CD38 has a genetic polymorphism, characterized by a C>G variation in the regulatory region of intron 1. The working hypothesis is that the presence of different alleles in CLL patients marks (or accounts for) some of the clinical heterogeneity. CD38 allele distribution in 248 Italian patients overlapped with that of the controls (n = 232), suggesting that susceptibility to CLL is not influenced by CD38 genotype. Stratification of patients according to markers of unfavorable prognosis constantly resulted in a significantly higher frequency of the rare G allele. Furthermore, analysis of clinical parameters showed that G allele is independently associated with nodal/splenic involvement. The highest G allele frequency was observed in the 16 patients of the cohort that developed Richter syndrome (RS). Five-year cumulative incidence of transformation was significantly higher in G allele carriers than in CC homozygotes. Multivariate analysis on a total of 30 RS patients confirmed that the probability of transformation is strongly associated with G allele, likely representing an independent risk factor for RS development.
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U2 - 10.1182/blood-2008-01-129726
DO - 10.1182/blood-2008-01-129726
M3 - Article
C2 - 18424664
AN - SCOPUS:47049131482
VL - 111
SP - 5646
EP - 5653
JO - Blood
JF - Blood
SN - 0006-4971
IS - 12
ER -