Super-Enhancer-Driven SOX4/SMAD3 Mediate Membrane Remodeling by Regulating Phospholipid Metabolism to Accelerate Leukemia Progression - PubMed
11 hours ago
- #transcription-factors
- #leukemia
- #membrane-remodeling
- Chronic myeloid leukemia (CML) progresses from chronic phase (CP) to blast phase (BP), with BP being more resistant to treatment.
- Super-enhancer-driven transcription factors SOX4 and SMAD3 are identified as key regulators in CML-BP.
- SOX4 and SMAD3 form a positive feedback loop by binding to each other's super-enhancers and promoters.
- This axis promotes leukemic progression by enhancing AXL transcription and activating AKT/ERK/STAT5 signaling.
- SOX4/SMAD3 also upregulate LPCAT1, which remodels membrane phospholipids to facilitate AXL localization.
- The AXL inhibitor Bemcentinib shows promise in suppressing CML-BP progression in both in vitro and in vivo models.