CORRESPONDENCE

AML is associated with several genetic and epi-genetic events that result in malignant transfor-mation of hematopoietic cells. In particular, transcription factors and epigenetic regulators involved in normal hematopoiesis are often found to be mutated, leading to the formation of leukemic stem cells and the accumulation of immature blasts (Estey and Döhner, 2006). Translocations involving the mixed lineage leukemia (MLL) gene at chromosome band 11q23 are among the most frequent lesions (10%) in AML and are associated with poor prognosis. More than 50 genes that fuse with MLL have been identified, of which ENL, ELL, AF6, AF9, and AF10 are the most frequent part-ners (Krivtsov and Armstrong, 2007; Muntean and Hess, 2012). Specifically, these fusions result in the expression of chimeric proteins in which the N terminus of the MLL protein is fused in-frame to the C terminus of the partner protein, thereby destroying the H3K4 histone methyl-transferase activity of the full-length MLL, while retaining its target selectivity for a subset of MLL-targets genes (Ayton et al., 2004; Slany, 2009). In line with this, the constitutive recruit-ment of the chimeric fusion proteins is believed to facilitate sustained expression of a subset of genes normally targeted by wild-type MLL re-sulting in leukemic transformation (Wang et al., 2011). The oncogenic potential of MLL-fusion proteins is driven, in part, by the selective re-cruitment of DOT1L and subsequent methyla-tion of H3K79, which leads to the formation of H3K79me2/me3 i.e., histone marks nor-mally associated with activated gene expression (Nguyen and Zhang, 2011). This, in turn, drives the induction of an MLL-fusion–dependent program involving Hox genes of which Hoxa9 and its cofactor Meis1 have been reported to b