Histone Deacetylase 11 (HDAC11) as a Novel Molecular Target in Mantle Cell Lymphoma

Mantle Cell Lymphoma (MCL) is a B-cell Non-Hodgkin’s Lymphoma characterized by the translocation t(11;14)(q13;32) and a consequent Cyclin D1 over-expression. The clinical evolution of MCL is very aggressive, and currently there is no standard of care for this malignancy.

In spite of the known association of Histone Deacetylases (HDACs) and solid malignancy growth, little is known regarding the role of these enzymes in MCL. We recently found newest member of the HDAC family, HDAC11, a molecule with an unknown prior physiological role, is a strong transcriptional repressor of gene expression¹. Interestingly, we have found a significant over-expression of HDAC11 in murine as well as in human MCL cell lines. In primary cells from patients with MCL, we observed that higher levels of HDAC11 are associated with a more aggressive disease, while low expressions of HDAC11 are seen in patients with the indolent variant of MCL. Microarray analysis of cells in which HDAC11 expression was silenced revealed significant down regulation of specific genes involved in the control of apoptosis, cell cycle, methylation and B-cell survival. Critical genes regulated by HDAC11 include IL-10 and IL-6, cytokines known to be survival factors for malignant B-cells. In addition, we have unveiled a previously unknown association between HDAC11, cyclin D1, and Cyclin Dependent Kinase Inhibitors (CDKI), molecules that play a central role in the pathogenesis of MCL.