MINI REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research Topicm6A modification in immune cell-regulated inflammatory diseasesView all articles
Decoding m6A readers: roles of YTHDF proteins in leukemogenesis and cancer immunity
Provisionally accepted
- 1Kunming Medical University, Kunming, China
- 2University of Birmingham, Birmingham, United Kingdom
- 3Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Abstract N6-methyladenosine (m6A) is the most prevalent internal modification in eukaryotic mRNA and plays critical roles in post-transcriptional gene regulation. Among the m6A regulators, YTH domain family proteins (YTHDF1, YTHDF2, and YTHDF3) act as major "readers" that interpret m6A marks and dictate the fate of modified transcripts through coordinated control of mRNA translation, stability, and decay. Recent advances have uncovered multifaceted roles of YTHDF proteins in both physiological hematopoiesis and pathological leukemogenesis. YTHDF2 is essential for hematopoietic stem cell (HSC) self-renewal and lineage commitment by selectively degrading transcripts that constrain stemness, while dysregulated YTHDF activity contributes to leukemic stem cell maintenance, metabolic adaptation, and therapy resistance. In parallel, YTHDF1 and YTHDF3 have been implicated in shaping the leukemic transcriptome and cooperating with oncogenic signaling pathways to promote malignant transformation. Beyond intrinsic leukemic functions, accumulating evidence highlights the impact of YTHDF proteins on tumor immunity. By modulating dendritic cell antigen presentation, T cell activation, and immune checkpoint expression, YTHDF proteins orchestrate the tumor immune microenvironment and influence anti-tumor immunity.
Keywords: YTHDF, M6A, Hematopoietic Stem Cells, Leukemia, cancer immunity, immune checkpoint therapy, epitranscriptomic regulation
Received: 26 Aug 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Chen, Pu, Lian, Li and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiulin Jiang, xiujiang@coh.org
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.