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December 8, 2025BloodOpen Access

DDX6 undergoes phase separation to modulate metabolic plasticity and chemoresistance

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Authors

WLWei LiBGI Group (China)HZHonghai ZhangQufu Normal UniversityDLDong LeiHohai University

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Overview

Knockout of DDX6 influences PB assembly and enhances sensitivity to Ara-C in AML, suggesting targeting DDX6 may improve treatment outcomes.

Key Points

  • Examine how DDX6 phase separation affects metabolic plasticity and chemoresistance in acute myeloid leukemia.
  • Developed a CRISPR library targeting SG and PB proteins for in vitro and in vivo screenings.
  • Utilized fluorescence recovery after photobleaching and droplet formation assays to assess DDX6 LLPS capacity.
  • Conducted metabolic profiling and multi-omics analysis to evaluate the role of DDX6 in mRNA stability and metabolism.
  • Knockout of DDX6 decreased PB assembly and suppressed AML leukemogenesis without affecting normal hematopoiesis.
  • DDX6 knockdown increased sensitivity of AML cells to Ara-C treatment, indicating potential therapeutic relevance.
  • Identified BCAT1 as a critical transcript whose regulation by DDX6 is vital for maintaining BCAA metabolism.

Cite This Study

Li et al. (2025) studied this question.

synapsesocial.com/papers/69362f7d4fa91c937236e4fehttps://doi.org/10.1182/blood-2025-212
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Also Consider

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

  1. 1DDX6 undergoes phase separation to modulate metabolic plasticity and chemoresistance2025 · 6 citations
  2. 2Granulocyte maturation and splicing defects in DDX41-mutated leukemia2025
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  4. 4Disrupting CXCL12-DPP4-GPC3 axis redistributes leukemia stem cells and confines AML cells within bone marrow niche2025 · 1 citations
  5. 5The somatic DDX41 hot spot mutation (p.R525H) causes skewed differentiation into plasmacytoid dendritic cells in human iPSC and leukemia models2025