Abstract

Induction of fetal hemoglobin (HbF) ameliorates the clinical severity of β-thalassemias. Histone methyltransferase LSD1 enzyme removes methyl groups from the activating chromatin mark histone 3 lysine 4 at silenced genes, including the γ-globin genes. LSD1 inhibitor RN-1 induces HbF levels in cultured human erythroid cells. Here, the HbF-inducing activity of RN-1 was investigated in erythroid progenitor cells derived from β0-thalassemia/ hemoglobin E (HbE) patients. The significant and reproducible increases in γ-globin transcript and HbF expression upon RN-1 treatment were demonstrated in erythroid cells with divergent HbF baseline levels, the average of HbF induction was 17.7±0.8%. RN-1 at low concentration did not affect viability and proliferation of erythroid cells, but decreases in cell number were observed in cells treated with RN-1 at high concentration. Delayed terminal erythroid differentiation was revealed in β0-thalassemia/HbE erythroid cells treated with RN-1 as similar to other compounds that target LSD1 activity. Downregulation of repressors of γ- globin expression; NCOR1 and SOX6, was observed in RN-1 treatment. These findings provide proof of the concept that LSD1 epigenetic enzyme is a potential therapeutic target for β0-thalassemia/HbE patients.

Highlights

  • Introduction βThalassemia/hemoglobin E patients constitute one-half of the clinically severe β-thalassemias worldwide

  • M levels in cultured human erythroid cells. o Here, the HbF-inducing activity of RN-1 c was investigated in erythroid progenitor - cells derived from β0-thalassemia/ n hemoglobin E (HbE) patients

  • Downregulation of repressors of γglobin expression; NCOR1 and SOX6, was observed in RN-1 treatment. These findings provide proof of the concept that Lysine-specific histone demethylase 1 (LSD1) epigenetic enzyme is a potential therapeutic target for β0-thalassemia/Hemoglobin E (HbE) patients

Read more

Summary

Introduction

Introduction βThalassemia/hemoglobin E patients constitute one-half of the clinically severe β-thalassemias worldwide. O Here, the HbF-inducing activity of RN-1 c was investigated in erythroid progenitor - cells derived from β0-thalassemia/ n hemoglobin E (HbE) patients.

Results
Conclusion

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.