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.
基金：
NIH R01 grants [CA178454, CA182528, CA214965, GM071440]; Leukemia & Lymphoma Society (LLS) Special Fellowship; LLS Translational Research grant; American Cancer Society (ACS); ACS-IL Research Scholar grant; Gabrielle's Angel Foundation for Cancer Research; China Scholarship Council (CSC); Foundation of Innovation Team for Basic and Clinical Research of Zhejiang Province [2011R50015]
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外文
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出版当年[2017]版：
大类|1 区医学
小类|1 区细胞生物学1 区肿瘤学
最新[2023]版：
大类|1 区医学
小类|1 区细胞生物学1 区肿瘤学
第一作者：
第一作者机构：[1]Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA;[9]Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA;
通讯作者：
通讯机构：[1]Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA;[2]Univ Cincinnati, Coll Med, Dept Canc Biol, Cincinnati, OH 45219 USA;[3]Univ Chicago, Howard Hughes Med Inst, Dept Chem, Inst Biophys Dynam, 5841 S Maryland Ave, Chicago, IL 60637 USA;[4]Univ Chicago, Howard Hughes Med Inst, Dept Biochem, Inst Biophys Dynam, 5841 S Maryland Ave, Chicago, IL 60637 USA;[5]Univ Chicago, Howard Hughes Med Inst, Dept Mol Biol, Inst Biophys Dynam, 5841 S Maryland Ave, Chicago, IL 60637 USA;
推荐引用方式(GB/T 7714)：
Li Zejuan,Weng Hengyou,Su Rui,et al.FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N-6-Methyladenosine RNA Demethylase[J].CANCER CELL.2017,31(1):127-141.doi:10.1016/j.ccell.2016.11.017.
APA：
Li, Zejuan,Weng, Hengyou,Su, Rui,Weng, Xiaocheng,Zuo, Zhixiang...&Chen, Jianjun.(2017).FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N-6-Methyladenosine RNA Demethylase.CANCER CELL,31,(1)
MLA：
Li, Zejuan,et al."FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N-6-Methyladenosine RNA Demethylase".CANCER CELL 31..1(2017):127-141
医学