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December 8, 2025Blood

HMGA1 chromatin regulators drive transcriptional networks governing cell cycle progression, immune escape, and menin-inhibitor resistance in KMT2A-r Acute Myeloid Leukemia

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Authors

ZTZanshé ThompsonYDY. W. DuASAudrey-Ann Supreme

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Overview

Leukemic stem cell dynamics reveal HMGA1's role in immune escape and chromatin regulation in KMT2A-r AML, suggesting new therapies.

Key Points

  • This research aims to elucidate the role of HMGA1 in KMT2A-r AML and its potential as a therapeutic target.
  • Silenced HMGA1 using CRISPR or shRNA in KMT2A-r AML cell lines
  • Assessed leukemogenic properties in vitro and in mouse models
  • Conducted RNAseq and ATACseq multiomic studies
  • Utilized AI for drug prediction to target HMGA1 networks.
  • HMGA1 is overexpressed in KMT2A-r AML, positively correlating with leukemogenic gene targets
  • Silencing HMGA1 disrupts proliferation and induces differentiation markers
  • HMGA1 deficiency decreases leukemic engraftment and prolongs survival in mice
  • Activated transcriptional networks by HMGA1 include cell cycle progression and immune escape mechanisms.

Cite This Study

Thompson et al. (2025) studied this question.

synapsesocial.com/papers/693624d74fa91c937236d119https://doi.org/10.1182/blood-2025-5027
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