Jun 23, 2011 · Here we demonstrate using a tamoxifen-inducible Cre-mediated loss of function mouse model that DOT1L, an H3K79 methyltransferase, is required for both initiation and maintenance of MLL-AF9-induced leukemogenesis in vitro and in vivo.

Jul 12, 2011 · Here, we demonstrate an epigenetic lesion that specifically involves H3K79 methylation on MLL-fusion target genes. Loss of Dot1l selectively decreases expression of MLL fusion-driven transcriptional programs.

Mar 24, 2022 · Disrupting the methylation of telomeric silencing 1-like (DOT1L)-mediated histone H3 lysine 79 has been implicated in MLL fusion-mediated leukemogenesis. Recently, DOT1L has become an attractive therapeutic target for MLL-rearranged leukemias.

Aug 8, 2013 · Here we describe the characterization of EPZ-5676, a potent and selective aminonucleoside inhibitor of DOT1L histone methyltransferase activity. The compound has an inhibition constant value of 80 pM, and demonstrates 37 000-fold selectivity over all other methyltransferases tested.

Sep 21, 2021 · Histone lysine methylation functions at the interface of the extracellular environment and intracellular gene expression. DOT1L is a versatile histone H3K79 methyltransferase with a prominent role in MLL-fusion leukemia, yet little is known about how DOT1L responds to extracellular stimuli.

MLL-AF10 and MLL-ENL recruit DOT1L on DNA, inducing hypermethylation of H3K79 in MLL-r target genes such as HOXA and MEIS1. To overcome the drawbacks of conventional chemotherapeutic drugs, novel compounds have recently been developed to inhibit DOT1L and thus counteract leukaemic growth.

Jun 6, 2011 · Here we demonstrate using a tamoxifen-inducible Cre-mediated loss of function mouse model that DOT1L, an H3K79 methyltransferase, is required for both initiation and maintenance of MLL-AF9–induced leukemogenesis in vitro and in vivo.

Mar 24, 2022 · Studies have shown that the disruptor of telomeric silencing 1-like (DOT1L) is involved in MLL fusion-driven leukemogenesis. DOT1L is the only histone methyltransferase that specifically targets nucleosomal histone H3 lysine 79 (H3K79) for mono-, di-, or trimethylation (H3K79me1, me2, or me3) .

Jun 23, 2011 · Here we demonstrate using a tamoxifen-inducible Cre-mediated loss of function mouse model that DOT1L, an H3K79 methyltransferase, is required for both initiation and maintenance of MLL-AF9–induced leukemogenesis in vitro and in vivo.

Oct 22, 2020 · In this issue of Blood, Perner and colleagues show that 2 new DOT1L inhibitors with favorable administration routes and pharmacokinetic properties yield promising antileukemic activity in patient-derived xenograft (PDX) models of …