| First Author | Paris J | Year | 2019 |
| Journal | Cell Stem Cell | Volume | 25 |
| Issue | 1 | Pages | 137-148.e6 |
| PubMed ID | 31031138 | Mgi Jnum | J:293320 |
| Mgi Id | MGI:6452525 | Doi | 10.1016/j.stem.2019.03.021 |
| Citation | Paris J, et al. (2019) Targeting the RNA m(6)A Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia. Cell Stem Cell 25(1):137-148.e6 |
| abstractText | 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 human AML 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. |
