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.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Shen C,Sheng Y,Zhu AC,Robinson S,Jiang X,Dong L,Chen H,Su R,Yin Z,Li W,Deng X,Chen Y,Hu YC,Weng H,Huang H,Prince E,Cogle CR,Sun M,Zhang B,Chen CW,Marcucci G,He C,Qian Z,Chen Jdoi
10.1016/j.stem.2020.04.009subject
Has Abstractpub_date
2020-07-02 00:00:00pages
64-80.e9issue
1eissn
1934-5909issn
1875-9777pii
S1934-5909(20)30148-Xjournal_volume
27pub_type
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