| Literature DB >> 32402250 |
Chao Shen1, Yue Sheng2, Allen C Zhu3, Sean Robinson1, Xi Jiang4, Lei Dong1, Huiying Chen1, Rui Su1, Zhe Yin5, Wei Li1, Xiaolan Deng1, Yinhuai Chen6, Yueh-Chiang Hu6, Hengyou Weng1, Huilin Huang1, Emily Prince1, Christopher R Cogle2, Miao Sun7, Bin Zhang8, Chun-Wei Chen1, Guido Marcucci8, Chuan He9, Zhijian Qian10, Jianjun Chen11.
Abstract
N6-methyladenosine (m6A), the most abundant internal modification in mRNA, has been implicated in tumorigenesis. As an m6A demethylase, ALKBH5 has been shown to promote the development of breast cancer and brain tumors. However, in acute myeloid leukemia (AML), ALKBH5 was reported to be frequently deleted, implying a tumor-suppressor role. Here, we show that ALKBH5 deletion is rare in human AML; instead, ALKBH5 is aberrantly overexpressed in AML. Moreover, its increased expression correlates with poor prognosis in AML patients. We demonstrate that ALKBH5 is required for the development and maintenance of AML and self-renewal of leukemia stem/initiating cells (LSCs/LICs) but not essential for normal hematopoiesis. Mechanistically, ALKBH5 exerts tumor-promoting effects in AML by post-transcriptional regulation of its critical targets such as TACC3, a prognosis-associated oncogene in various cancers. Collectively, our findings reveal crucial functions of ALKBH5 in leukemogenesis and LSC/LIC self-renewal/maintenance and highlight the therapeutic potential of targeting the ALKBH5/m6A axis.Entities:
Keywords: ALKBH5; MYC; P21; TACC3; acute myeloid leukemia; hematopoietic stem cells (HSCs); leukemia stem cells (LSCs/LICs); m(6)A modification; normal hematopoiesis; prognosis
Mesh：
Substances：
Year: 2020 PMID： 32402250 PMCID： PMC7335338 DOI： 10.1016/j.stem.2020.04.009
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633