| First Author | Chen Z | Year | 2025 |
| Journal | Cell | Volume | 188 |
| Issue | 2 | Pages | 331-351.e30 |
| PubMed ID | 39694037 | Mgi Jnum | J:361349 |
| Mgi Id | MGI:7856353 | Doi | 10.1016/j.cell.2024.11.007 |
| Citation | Chen Z, et al. (2025) YTHDF2 promotes ATP synthesis and immune evasion in B cell malignancies. Cell 188(2):331-351.e30 |
| abstractText | Long-term durable remission in patients with B cell malignancies following chimeric antigen receptor (CAR)-T cell immunotherapy remains unsatisfactory, often due to antigen escape. Malignant B cell transformation and oncogenic growth relies on efficient ATP synthesis, although the underlying mechanisms remain unclear. Here, we report that YTHDF2 facilitates energy supply and antigen escape in B cell malignancies, and its overexpression alone is sufficient to cause B cell transformation and tumorigenesis. Mechanistically, YTHDF2 functions as a dual reader where it stabilizes mRNAs as a 5-methylcytosine (m(5)C) reader via recruiting PABPC1, thereby enhancing their expression and ATP synthesis. Concomitantly, YTHDF2 also promotes immune evasion by destabilizing other mRNAs as an N(6)-methyladenosine (m(6)A) reader. Small-molecule-mediated targeting of YTHDF2 suppresses aggressive B cell malignancies and sensitizes them to CAR-T cell therapy. |
