title: CD38 gene polymorphism and chronic lymphocytic leukemia: a role in transformation to Richter syndrome?
abstract: 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.
authors.affiliation: Department of Genetics, Biology, and Biochemistry, University of Torino Medical School, Turin, Italy.
authors.forename: Semra
authors.initials: S
authors.lastname: Aydin
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Luciana
authors.initials: L
authors.lastname: Bergui
authors.forename: Giovanni
authors.initials: G
authors.lastname: D'Arena
authors.forename: Enza
authors.initials: E
authors.lastname: Ferrero
authors.forename: Lisa
authors.initials: L
authors.lastname: Bonello
authors.forename: Paola
authors.initials: P
authors.lastname: Omedé
authors.forename: Domenico
authors.initials: D
authors.lastname: Novero
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
authors.forename: Silvia
authors.initials: S
authors.lastname: Deaglio
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D015331:Cohort Studies; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007558:Italy / Q000453:epidemiology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000453:epidemiology / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000453:epidemiology / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011379:Prognosis; D012307:Risk Factors; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D005819:Genetic Markers; D007376:Interleukin-2; D008562:Membrane Glycoproteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1