CD49d is overexpressed by trisomy 12 chronic lymphocytic leukemia cells: evidence for a methylation-dependent regulation mechanism.

Antonella Zucchetto, Chiara Caldana, Dania Benedetti, Erika Tissino, Francesca Maria Rossi, Evelyn Hutterer, Federico Pozzo, Riccardo Bomben, Michele Dal Bo, Giovanni D'Arena, Francesco Zaja, Gabriele Pozzato, Francesco Di Raimondo, Tanja N. Hartmann, Davide Rossi, Gianluca Gaidano, Giovanni Del Poeta, Valter Gattei

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)3317-3321
Number of pages5
JournalBlood
Volume122
Issue number19
Publication statusPublished - Nov 7 2013

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology
  • Medicine(all)

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