TY - JOUR
T1 - CD49d IS OVEREXPRESSED BY TRISOMY 12 CHRONIC LYMPHOCYTIC LEUKEMIA CELLS: EVIDENCE FOR A METHYLATION-DEPENDENT REGULATION MECHANISM
AU - Zucchetto, A
AU - Caldana, C
AU - Benedetti, D
AU - Tissino, E
AU - FM, Rossi
AU - Hutterer, E
AU - Pozzo, F
AU - Bomben, R
AU - Dal, Bo M
AU - D'Arena, G
AU - Zaja, F
AU - Pozzato, G
AU - Di, Raimondo F
AU - TN, Hartmann
AU - ROSSI, Davide
AU - GAIDANO, Gianluca
AU - Del, Poeta G
AU - Gattei, V.
N1 - Publisher Copyright:
© 2013 by The American Society of Hematology.
PY - 2013
Y1 - 2013
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.
UR - https://iris.uniupo.it/handle/11579/39361
U2 - 10.1182/blood-2013-06-507335
DO - 10.1182/blood-2013-06-507335
M3 - Article
SN - 0006-4971
VL - 122
SP - 3317
EP - 3321
JO - Blood
JF - Blood
IS - 19
ER -