Targeting the RNA m(6)A Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia
- Title
- Targeting the RNA m(6)A Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia
- Author
- 최준호
- Keywords
- MESSENGER-RNA; NUCLEAR-RNA; EXPRESSION; TRANSLATION; DIFFERENTIATION; HIF-1-ALPHA; GENES; N6-METHYLADENOSINE; LEUKEMOGENESIS; IDENTIFICATION
- Issue Date
- 2019-07
- Publisher
- CELL PRESS
- Citation
- CELL STEM CELL, v. 25, no. 1, Page. 137-148
- Abstract
- Acute myeloid leukemia (AML) is an aggressive clonal disorder of hematopoietic stem cells (HSCs) and primitive progenitors that blocks their myeloid differentiation, generating self-renewing leukemic stem cells (LSCs). Here, we show that the mRNA m(6)A reader YTHDF2 is overexpressed in a broad spectrum of humanAML and is required for disease initiation as well as propagation in mouse and human AML. YTHDF2 decreases the half-life of diverse m(6)A transcripts that contribute to the overall integrity of LSC function, including the tumor necrosis factor receptor Tnfrsf2, whose upregulation in Ythdf2-deficient LSCs primes cells for apoptosis. Intriguingly, YTHDF2 is not essential for normal HSC function, with YTHDF2 deficiency actually enhancing HSC activity. Thus, we identify YTHDF2 as a unique therapeutic target whose inhibition selectively targets LSCs while promoting HSC expansion.
- URI
- https://www.sciencedirect.com/science/article/pii/S1934590919301201?via%3Dihubhttps://repository.hanyang.ac.kr/handle/20.500.11754/152292
- ISSN
- 1934-5909; 1875-9777
- DOI
- 10.1016/j.stem.2019.03.021
- Appears in Collections:
- COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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