TY - JOUR
T1 - CD49d is overexpressed by trisomy 12 chronic lymphocytic leukemia cells
T2 - evidence for a methylation-dependent regulation mechanism.
AU - Zucchetto, Antonella
AU - Caldana, Chiara
AU - Benedetti, Dania
AU - Tissino, Erika
AU - Rossi, Francesca Maria
AU - Hutterer, Evelyn
AU - Pozzo, Federico
AU - Bomben, Riccardo
AU - Dal Bo, Michele
AU - D'Arena, Giovanni
AU - Zaja, Francesco
AU - Pozzato, Gabriele
AU - Di Raimondo, Francesco
AU - Hartmann, Tanja N.
AU - Rossi, Davide
AU - Gaidano, Gianluca
AU - Del Poeta, Giovanni
AU - Gattei, Valter
PY - 2013/11/7
Y1 - 2013/11/7
N2 - CD49d is a negative prognosticator in chronic lymphocytic leukemia (CLL), expressed by ~40% of CLL cases and associated with aggressive, accelerated clinical courses. In this study, analyzing CD49d expression in a wide CLL cohort (n = 1200) belonging to different cytogenetic groups, we report that trisomy 12 CLL almost universally expressed CD49d and were characterized by the highest CD49d expression levels among all CD49d(+) CLL. Through bisulfite genomic sequencing, we demonstrated that, although CD49d(+)/trisomy 12 CLL almost completely lacked methylation of the CD49d gene, CD49d(-)/no trisomy 12 CLL were overall methylated, the methylation levels correlating inversely to CD49d expression (P = .0001). Consistently, CD49d expression was recovered in CD49d(-) hypermethylated CLL cells upon in vitro treatment with the hypomethylating agent 5-aza-2'-deoxycytidine. This may help explain the clinicobiological features of trisomy 12 CLL, including the high rates of cell proliferation and disease progression, lymph node involvement, and predisposition to Richter syndrome transformation.
AB - CD49d is a negative prognosticator in chronic lymphocytic leukemia (CLL), expressed by ~40% of CLL cases and associated with aggressive, accelerated clinical courses. In this study, analyzing CD49d expression in a wide CLL cohort (n = 1200) belonging to different cytogenetic groups, we report that trisomy 12 CLL almost universally expressed CD49d and were characterized by the highest CD49d expression levels among all CD49d(+) CLL. Through bisulfite genomic sequencing, we demonstrated that, although CD49d(+)/trisomy 12 CLL almost completely lacked methylation of the CD49d gene, CD49d(-)/no trisomy 12 CLL were overall methylated, the methylation levels correlating inversely to CD49d expression (P = .0001). Consistently, CD49d expression was recovered in CD49d(-) hypermethylated CLL cells upon in vitro treatment with the hypomethylating agent 5-aza-2'-deoxycytidine. This may help explain the clinicobiological features of trisomy 12 CLL, including the high rates of cell proliferation and disease progression, lymph node involvement, and predisposition to Richter syndrome transformation.
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M3 - Article
C2 - 24068493
AN - SCOPUS:84891679581
VL - 122
SP - 3317
EP - 3321
JO - Blood
JF - Blood
SN - 0006-4971
IS - 19
ER -