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September 10, 2025Cancer Research

Loss of SETD8 Impairs Mitochondrial Homeostasis to Suppress Leukemia Stem Cell Function in t(8;21) Acute Myeloid Leukemia

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Authors

YSYongwei SuSLS LiLWLei Wang

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Overview

Research demonstrates that SETD8 impacts mitochondrial homeostasis and leukemic stem cell survival in t(8;21) AML, suggesting therapeutic interventions.

Key Points

  • Loss of SETD8 impairs the survival and self-renewal of leukemic stem cells in t(8;21) AML, affecting overall leukemia progression.
  • Genetic deletion or inhibition of SETD8 significantly reduced leukemic stem cell characteristics in both mouse models and primary human cells.
  • SETD8 enhances mitochondrial homeostasis by promoting the expression of RHOT1, indicating its pivotal role in gene regulation.
  • These findings highlight the potential to target SETD8 for therapeutic strategies aimed at eliminating leukemic stem cells.

Cite This Study

Su et al. (2025) studied this question.

synapsesocial.com/papers/68c1dd9254b1d3bfb60fbfd8https://doi.org/10.1158/0008-5472.can-24-3659
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Also Consider

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

  1. 1SETD2 deficiency in chronic myeloid leukemia (CML) contributes to tyrosine kinase inhibitor (TKI) resistance and disease acceleration by enhancing genetic instability and rewiring cellular metabolism and might be a novel biomarker of high risk disease since diagnosis2025
  2. 2SETD8 inhibits apoptosis and ferroptosis of Ewing’s sarcoma through YBX1/RAC3 axis2024 · 4 citations
  3. 3Histone lactylation boosted SET8 potentiates carcinogenesis and angiogenesis of pancreatic ductal adenocarcinoma by cooperating with MTA1/NuRD complex2026
  4. 4The SETD2 L1609P mutation found in leukemia disrupts methyltransferase activity and reduces histone H3K36 trimethylation2026
  5. 5SETD8 inhibition targets cancer cells with increased rates of ribosome biogenesis2024