Published on Jan. 9, 2017 in Cancer Cell volume 31(1).

PubMed ID: 28017614

DOI: 10.1016/j.ccell.2016.11.017

Abstract:

N(6)-Methyladenosine (m(6)A) represents the most prevalent internal modification inmammalian mRNAs. Despite its functional importance in various fundamentalbioprocesses, the studies of m(6)A in cancer have been limited. Here we show thatFTO, as an m(6)A demethylase, plays a critical oncogenic role in acute myeloidleukemia (AML). FTO is highly expressed in AMLs with t(11q23)/MLL rearrangements,t(15;17)/PML-RARA, FLT3-ITD, and/or NPM1 mutations. FTO enhances leukemiconcogene-mediated cell transformation and leukemogenesis, and inhibitsall-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulatingexpression of targets such as ASB2 and RARA by reducing m(6)A levels in these mRNAtranscripts. Collectively, our study demonstrates the functional importance of them(6)A methylation and the corresponding proteins in cancer, and provides profoundinsights into leukemogenesis and drug response.CI - Copyright © 2017 Elsevier Inc. All rights reserved.