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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5646-5653.
Prepublished online as a Blood First Edition Paper on April 18, 2008; DOI 10.1182/blood-2008-01-129726.
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Submitted January 3, 2008
Accepted April 8, 2008
CD38 gene polymorphism and chronic lymphocytic leukemia: a role in transformation to Richter's syndrome?
Semra Aydin, Davide Rossi, Luciana Bergui, Giovanni D'Arena, Enza Ferrero, Lisa Bonello, Paola Omede, Domenico Novero, Fortunato Morabito, Antonino Carbone, Gianluca Gaidano, Fabio Malavasi*, and Silvia Deaglio
Dept. of Genetics, Biology and Biochemistry, University of Torino School of Medicine, Turin, Italy
Division of Hematology, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy
Dept. of Medicine and Experimental Oncology, University of Torino School of Medicine, Turin, Italy
Division of Hematology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
Research Center for Experimental Medicine, University of Torino School of Medicine, Turin, Italy
Dept. of Pathology, Molinette Hospital, Turin, Italy
Hematology Unit, Cosenza Hospital, Cosenza, Italy
Dept. of Pathology, National Cancer Institute, Milan, Italy
* Corresponding author; email: fabio.malavasi{at}unito.it.
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's syndrome (RS). 5-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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