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Publication : FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N<sup>6</sup>-Methyladenosine RNA Demethylase.

First Author  Li Z Year  2017
Journal  Cancer Cell Volume  31
Issue  1 Pages  127-141
PubMed ID  28017614 Mgi Jnum  J:238414
Mgi Id  MGI:5819303 Doi  10.1016/j.ccell.2016.11.017
Citation  Li Z, et al. (2017) FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N6-Methyladenosine RNA Demethylase. Cancer Cell 31(1):127-141
abstractText  N6-Methyladenosine (m6A) represents the most prevalent internal modification in mammalian mRNAs. Despite its functional importance in various fundamental bioprocesses, the studies of m6A in cancer have been limited. Here we show that FTO, as an m6A 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 m6A levels in these mRNA transcripts. Collectively, our study demonstrates the functional importance of the m6A methylation and the corresponding proteins in cancer, and provides profound insights into leukemogenesis and drug response.
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