CD38 gene polymorphism and chronic lymphocytic leukemia: a role in transformation to Richter syndrome?
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.
Aydin
Semra
S
Department of Genetics, Biology, and Biochemistry, University of Torino Medical School, Turin, Italy.
Rossi
Davide
D
Bergui
Luciana
L
D'Arena
Giovanni
G
Ferrero
Enza
E
Bonello
Lisa
L
Omedé
Paola
P
Novero
Domenico
D
Morabito
Fortunato
F
Carbone
Antonino
A
Gaidano
Gianluca
G
Malavasi
Fabio
F
Deaglio
Silvia
S
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
D005819:Genetic Markers; D007376:Interleukin-2; D008562:Membrane Glycoproteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1