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Updated: Jul 13, 2026

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
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RXR is an essential component of the oncogenic PML/RARA complex in vivo

Jun Zhu1, Rihab Nasr, Laurent Pérès

  • 1CNRS/University Paris VII UMR 7151, laboratoire associé N11 de la Ligue contre le Cancer, Hôpital St. Louis, 1, avenue Claude Vellefaux, 75475 Paris Cedex 10, France.

Cancer Cell
|July 7, 2007
PubMed

Insights

Retinoic acid receptor (RXR) is unexpectedly crucial for PML/RARA

Area of Science:

  • Molecular Biology
  • Hematopoiesis
  • Cancer Biology

Background:

  • The PML/RARA oncoprotein drives acute promyelocytic leukemia (APL).
  • PML/RARA's interaction with coreceptors like RXR is critical for its function.
  • RXR's precise role in PML/RARA-mediated leukemogenesis remains incompletely understood.

Purpose of the Study:

  • To investigate the essential role of RXR in PML/RARA-induced APL development in vivo.
  • To elucidate how RXR influences PML/RARA's DNA binding and transcriptional activity.
  • To determine RXR's impact on differentiation therapy for APL.

Main Methods:

  • Generation of transgenic mouse models expressing wild-type or RXR-binding-defective PML/RARA.
  • Ex vivo transformation of primary hematopoietic progenitors.
  • Analysis of APL development, differentiation, and gene expression.
  • Assessment of PML/RARA and RXR posttranslational modifications.

Main Results:

  • PML/RARA mutants lacking RXR binding fail to induce APL in mice but transform cells ex vivo.
  • RXR enhances PML/RARA's DNA binding and is essential for rexinoid-induced differentiation.
  • Absence of RXR leads to monocytic differentiation instead of granulocytic differentiation in treated cells.
  • PML/RARA promotes RXR sumoylation, suggesting a role in deregulated transcription.

Conclusions:

  • RXR is unexpectedly required for PML/RARA's in vivo leukemogenic activity.
  • RXR plays a critical role in PML/RARA-driven APL pathogenesis and differentiation.
  • Targeting RXR interactions may offer novel therapeutic strategies for APL.

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