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December 8, 2025Blood

STAG2 mutation preserves a stem cell phenotype in FLT3-ITD-mediated MDS to leukemia transformation

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Authors

VSVarun SudunaguntaRBRobert L. Bowman

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Overview

Sequential mutagenesis reveals STAG2 mutation preserves HSC during leukemia transformation, suggesting new therapeutic insights.

Key Points

  • To investigate how STAG2 mutation impacts hematopoietic stem cells during leukemia transformation.
  • Developed a murine model of sequential mutagenesis with Stag2 and Flt3ITD mutations.
  • Monitored conditions for a MDS phase followed by leukemia transformation phase.
  • Analyzed HSC and progenitor populations using scRNAseq and bulk RNAseq.
  • Conducted flow cytometry for characterizing mutant HSCs.
  • Performed competitive transplantation experiments.
  • STAG2 mutation preserved HSC population during transformation, unlike FLT3ITD.
  • Notable depletion of HSCs and expansion of myeloid progenitors observed in FLT3ITD.
  • Detection of a transcriptionally defined HSC population in Stag21stITD2nd samples.
  • Reduced cycling of Stag21stITD2nd HSCs compared to wild-type before FLT3ITD acquisition.
  • Competitive transplantation showed different reconstitution patterns between Stag21stITD2nd and FLT3ITD derived cells.

Cite This Study

Sudunagunta et al. (2025) studied this question.

synapsesocial.com/papers/69362f3d4fa91c937236d4b6https://doi.org/10.1182/blood-2025-3242
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Also Consider

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

  1. 1Enhanced FLI1 accessibility mediates STAG2-mutant leukemogenesis2025
  2. 2Activation of endogenous retroviral elements drives inflammation and transformation in STAG2-mutant myeloid malignancies2025 · 1 citations
  3. 3ST2 promotes leukemia transformation by reshaping the immune landscape in Acute Myeloid Leukemia2025
  4. 4A CRISPR-Based Humanized Model Reveals Cooperative Role of STAG2 Loss in Familial GATA2-Deficient MDS Progression2026
  5. 5STAG2 mutations reshape the cohesin-structured spatial chromatin architecture to drive gene regulation in acute myeloid leukemia2024 · 27 citations