@article{19daf2de7c0d4b819ce2eb597a356c3b,
title = "FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N 6 -Methyladenosine RNA Demethylase",
abstract = " N 6 -Methyladenosine (m 6 A) represents the most prevalent internal modification in mammalian mRNAs. Despite its functional importance in various fundamental bioprocesses, the studies of m 6 A in cancer have been limited. Here we show that FTO, as an m 6 A demethylase, plays a critical oncogenic role in acute myeloid leukemia (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 leukemic oncogene-mediated cell transformation and leukemogenesis, and inhibits all-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulating expression of targets such as ASB2 and RARA by reducing m 6 A levels in these mRNA transcripts. Collectively, our study demonstrates the functional importance of the m 6 A methylation and the corresponding proteins in cancer, and provides profound insights into leukemogenesis and drug response. ",
keywords = "AML, ASB2, ATRA, cell differentiation, FTO, leukemogenesis, m6A, RARA, RNA modification, RNA stability",
author = "Zejuan Li and Hengyou Weng and Rui Su and Xiaocheng Weng and Zhixiang Zuo and Chenying Li and Huilin Huang and Sigrid Nachtergaele and Lei Dong and Chao Hu and Xi Qin and Lichun Tang and Yungui Wang and Hong, {Gia Ming} and Hao Huang and Xiao Wang and Ping Chen and Sandeep Gurbuxani and Stephen Arnovitz and Yuanyuan Li and Shenglai Li and Jennifer Strong and Neilly, {Mary Beth} and Larson, {Richard A.} and Xi Jiang and Pumin Zhang and Jie Jin and Chuan He and Jianjun Chen",
note = "Funding Information: We thank Dr. Michelle M. Le Beau for providing primary AML patient samples and James Mulloy for providing the MA9/FLT3-ITD AML cell line. This work was supported in part by NIH R01 grants CA178454 (J.C.), CA182528 (J.C.), CA214965 (J.C.), and GM071440 (C.H.), Leukemia & Lymphoma Society (LLS) Special Fellowship (Z.L.), LLS Translational Research grant (J.C.), American Cancer Society (ACS) Research Scholar grant (J.C.), ACS-IL Research Scholar grant (Z.L.), Gabrielle's Angel Foundation for Cancer Research (J.C., Z.L., X.J., and H.H.), China Scholarship Council (CSC) visiting scholar (X.W.), and Foundation of Innovation Team for Basic and Clinical Research of Zhejiang Province (grant 2011R50015) (J.J.). S.N. is an HHMI Fellow of the Damon Runyon Cancer Research Foundation (DRG-2215-15). C.H. is an investigator of the Howard Hughes Medical Institute (HHMI). Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = jan,
day = "9",
doi = "10.1016/j.ccell.2016.11.017",
language = "English (US)",
volume = "31",
pages = "127--141",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "1",
}