Am80 (tamibarotene) and ATRA induce highly similar molecular responses and myeloid differentiation in non-APL AML, enhanced by LSD1/GCN5 inhibition and increased RARA expression - Summary - MDSpire

Am80 (tamibarotene) and ATRA induce highly similar molecular responses and myeloid differentiation in non-APL AML, enhanced by LSD1/GCN5 inhibition and increased RARA expression

  • By

  • Faezeh Ghazvini Zadegan

  • Clara Stanko

  • Franziska Fiedler

  • Laura Ölsner

  • Setenay Gupse Özcan

  • Jacqueline Schütt

  • Tina M. Schnöder

  • Yordan Sbirkov

  • Lukasz Szymanski

  • Sven Stengel

  • Peter Dittrich

  • Jörg P. Müller

  • Florian H. Heidel

  • Andreas Hochhaus

  • Sebastian Scholl

  • Ulf Schnetzke

  • Annamaria Brioli

  • Tino Schenk

  • June 27, 2026

  • 0 min

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Objective:

To investigate whether the RARA-selective agonist Am80 can overcome the differentiation block in non-APL AML compared with the pan-RAR agonist ATRA, and to assess the impact of LSD1 and GCN5 inhibition on these responses.

Approach:
  • Study Design: The study examined the effects of Am80 and ATRA in 6 AML cell lines and 67 primary AML samples, focusing on RARA and RARG expression.
  • Treatment Methods: Cells were treated with ATRA, Am80, LSD1 inhibitor (GSK-LSD1), and GCN5 inhibitor (MB3) for 3 days.
  • Analysis Techniques: Flow cytometry was used for surface marker expression, and RNA-seq was performed for gene expression analysis.
Key Findings:
  • RARA was the most abundant retinoic acid receptor in the analyzed samples, with expression levels approximately fivefold higher than RARG.
  • A significant correlation was observed between RARA and RARG expression, both co-expressed with RXRA.
  • Inhibition of LSD1 and GCN5 was shown to enhance the responsiveness to ATRA and Am80.
Interpretation:

Limitations:
  • The study primarily focused on a limited number of AML cell lines and primary samples, which may not represent all AML subtypes.
  • Further clinical validation is needed to confirm the efficacy of Am80 and the impact of LSD1/GCN5 inhibition in a broader patient population.
Conclusion:

Original Source(s)

Am80 (tamibarotene) and ATRA induce highly similar molecular responses and myeloid differentiation in non-APL AML, enhanced by LSD1/GCN5 inhibition and increased RARA expression

  • by Faezeh Ghazvini Zadegan, Clara Stanko, Franziska Fiedler, Laura Ölsner, Setenay Gupse Özcan, Jacqueline Schütt, Tina M. Schnöder, Yordan Sbirkov, Lukasz Szymanski, Sven Stengel, Peter Dittrich, Jörg P. Müller, Florian H. Heidel, Andreas Hochhaus, Sebastian Scholl, Ulf Schnetzke, Annamaria Brioli, Tino Schenk

  • June 27, 2026

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