Epigenetic regulation of protein translation in KMT2A- rearranged AML

Rearrangements of KMT2A (MLL1) occur in 10% of AML and ALL, and 70% of infant ALL. With few exceptions, KMT2A rearrangements are associated with a poor prognosis, and KMT2A-rearranged (KMT2A-r) leukemias have been the target of substantial drug development efforts and clinical research without much impact yet on survival 1. KMT2A fusions are strongly transforming 2, likely due to the profound epigenetic changes they induce. Key histone lysine methyltransferases (KMTs) involved in KMT2A-fusion mediated leukemogenesis are the H3K79 KMT4 (hereafter referred to as DOT1L) 3-6 and the H3K27 KMT6 (hereafter referred to as EZH2) 7-11.

Source: Experimental Hematology - May 9, 2020 Category: Hematology Authors: Alexandra Lenard, Hongbo Michael Xie, Taylor Pastuer, Tyler Shank, Clara Libbrecht, Molly Kingsley, Simone S. Riedel, Zuo-Fei Yuan, Nan Zhu, Tobias Neff, Kathrin M. Bernt Source Type: research