Journal
BLOOD
Volume 122, Issue 19, Pages 3317-3321Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-06-507335
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Funding
- Ministero della Salute Ricerca Finalizzata I. R. C. C. S.
- Austrian Science Fund (FWF) [W1213] Funding Source: Austrian Science Fund (FWF)
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
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CD49d is a negative prognosticator in chronic lymphocytic leukemia (CLL), expressed by similar to 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(-)/notrisomy 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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