Modomics - A Database of RNA Modifications

Published on July 3, 2019 in Cell Stem Cell volume 25(1).

PubMed ID: 31031138

DOI: S1934-5909(19)30120-1


Acute myeloid leukemia (AML) is an aggressive clonal disorder of hematopoietic stemcells (HSCs) and primitive progenitors that blocks their myeloid differentiation,generating self-renewing leukemic stem cells (LSCs). Here, we show that the mRNAm(6)A reader YTHDF2 is overexpressed in a broad spectrum of human AML and isrequired for disease initiation as well as propagation in mouse and human AML.YTHDF2 decreases the half-life of diverse m(6)A transcripts that contribute to theoverall integrity of LSC function, including the tumor necrosis factor receptorTnfrsf2, whose upregulation in Ythdf2-deficient LSCs primes cells for apoptosis.Intriguingly, YTHDF2 is not essential for normal HSC function, with YTHDF2deficiency actually enhancing HSC activity. Thus, we identify YTHDF2 as a uniquetherapeutic target whose inhibition selectively targets LSCs while promoting HSCexpansion.CI - Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.