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December 8, 2025BloodOpen Access

A new HDAC1/2 degrader increases HbF production in human CD34⁺ cells at non-cytotoxic, differentiation-preserving dose

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Authors

MBMarina Dorigatti BorgesFCFernando Ferreira Costa

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Overview

In vitro treatment with HDAC1/2 degrader ARP-47 increased HbF in CD34+ cells, suggesting a new approach for β-hemoglobinopathies.

Key Points

  • This research aims to evaluate the effects of a novel HDAC1/2 degrader on HbF production in CD34+ cells.
  • Tested ARP-47 in vitro during erythroid differentiation of human CD34+ cells from healthy donors.
  • Analyzed viability, proliferation, and erythroid differentiation via flow cytometry.
  • Quantified mRNA levels of HBG1/2, HBB, HDAC1, and HDAC2 using qPCR.
  • Assessed protein levels of γ-globin, HDAC1, and HDAC2 by Western blot.
  • ARP-47 treatment increased percentage of F-cells significantly at 10 nM compared to DMSO.
  • HBG1/2 mRNA showed a 2.5-fold increase after treatment with ARP-47 at 10 nM.
  • Western blot analysis revealed a 2-fold increase in γ-globin protein due to ARP-47 treatment.

Cite This Study

Borges et al. (2025) studied this question.

synapsesocial.com/papers/69362f744fa91c937236e2cchttps://doi.org/10.1182/blood-2025-6491
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