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December 8, 2025Blood

Targeting the METTL1/m7G axis as a therapeutic strategy in myeloid leukemia

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Authors

LRLili RenFNFrancesco NaiHBHongjie Bi

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Overview

This research demonstrates that targeting METTL1 reduces leukemia stem cell frequency in myeloid leukemia, suggesting it could be a novel therapeutic approach.

Key Points

  • This research aims to explore the role of METTL1 in the maintenance of leukemia stem cells and its potential as a therapeutic target in myeloid leukemia.
  • Utilized CRISPR/Cas9 screening to identify critical regulators in AML cells.
  • Conducted in vitro and in vivo experiments using METTL1 inhibitors in myeloid leukemia models.
  • Performed transcriptomic analysis and small-molecule inhibitor screenings with over 264,000 compounds.
  • METTL1 depletion significantly reduced leukemia stem cell frequency and delayed leukemia onset in animal models.
  • M1i, the lead METTL1 inhibitor, demonstrated strong anti-leukemic effects with low nanomolar IC50 values.
  • Targeting the METTL1/m7G axis suppressed key signaling pathways involved in leukemia progression.

Cite This Study

Ren et al. (2025) studied this question.

synapsesocial.com/papers/693624dd4fa91c937236d23ahttps://doi.org/10.1182/blood-2025-2539
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Targeting METTL3 disrupts oncogenic transcriptional programs and activates immune and apoptotic pathways in Acute Myeloid Leukemia2025
  2. 2The role of METTL14 in the progression of chronic myeloid leukemia2025 · 4 citations
  3. 3METTL13 Promotes Pre-Leukemic Transformation and the Development of Pediatric Leukemia2025
  4. 4METTL16-mediated inhibition of MXD4 promotes leukemia through activation of the MYC-MAX axis2025
  5. 5Targeting O-GlcNAcylated METTL3 impedes MDS/AML progression via diminishing SRSF1 m6A modification2025 · 1 citations