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Hematology Reports
Volume 13
Issue 4
10.4081/hr.2021.9215
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Hematology Reports is published by MDPI from Volume 14 Issue 1 (2022). Previous articles were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence, and they are hosted by MDPI on mdpi.com as a courtesy and upon agreement with PAGEPress.
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Article

Lysine-Specific Histone Demethylase 1 Inhibition Enhances Robust Fetal Hemoglobin Induction in Human β0-Thalassemia/Hemoglobin E Rrythroid Cells

by
Woratree Kaewsakulthong
1,
Phitchapa Pongpaksupasin
2,
Tiwaporn Nualkaew
2,
Suradej Hongeng
3,
Suthat Fucharoen
2,
Natee Jearawiriyapaisarn
2 and
Orapan Sripichai
2,4,*
1
Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
2
Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhonpathom, Thailand
3
Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
4
National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi 11000, Thailand
*
Author to whom correspondence should be addressed.
Hematol. Rep. 2021, 13(4), 9215; https://doi.org/10.4081/hr.2021.9215
Submission received: 26 April 2021 / Revised: 24 September 2021 / Accepted: 13 October 2021 / Published: 26 November 2021

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/HbE patients. The significant and reproducible increases in γ-globin transcript and HbF expression upon RN-1 treatment was 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 was 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 a proof of concept that a LSD1 epigenetic enzymes is a potential therapeutic target for β0-thalassemia/HbE patients.
Keywords: thalassemia, erythroid, fetal hemoglobin, LSD1, RN-1 thalassemia, erythroid, fetal hemoglobin, LSD1, RN-1

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MDPI and ACS Style

Kaewsakulthong, W.; Pongpaksupasin, P.; Nualkaew, T.; Hongeng, S.; Fucharoen, S.; Jearawiriyapaisarn, N.; Sripichai, O. Lysine-Specific Histone Demethylase 1 Inhibition Enhances Robust Fetal Hemoglobin Induction in Human β0-Thalassemia/Hemoglobin E Rrythroid Cells. Hematol. Rep. 2021, 13, 9215. https://doi.org/10.4081/hr.2021.9215

AMA Style

Kaewsakulthong W, Pongpaksupasin P, Nualkaew T, Hongeng S, Fucharoen S, Jearawiriyapaisarn N, Sripichai O. Lysine-Specific Histone Demethylase 1 Inhibition Enhances Robust Fetal Hemoglobin Induction in Human β0-Thalassemia/Hemoglobin E Rrythroid Cells. Hematology Reports. 2021; 13(4):9215. https://doi.org/10.4081/hr.2021.9215

Chicago/Turabian Style

Kaewsakulthong, Woratree, Phitchapa Pongpaksupasin, Tiwaporn Nualkaew, Suradej Hongeng, Suthat Fucharoen, Natee Jearawiriyapaisarn, and Orapan Sripichai. 2021. "Lysine-Specific Histone Demethylase 1 Inhibition Enhances Robust Fetal Hemoglobin Induction in Human β0-Thalassemia/Hemoglobin E Rrythroid Cells" Hematology Reports 13, no. 4: 9215. https://doi.org/10.4081/hr.2021.9215

APA Style

Kaewsakulthong, W., Pongpaksupasin, P., Nualkaew, T., Hongeng, S., Fucharoen, S., Jearawiriyapaisarn, N., & Sripichai, O. (2021). Lysine-Specific Histone Demethylase 1 Inhibition Enhances Robust Fetal Hemoglobin Induction in Human β0-Thalassemia/Hemoglobin E Rrythroid Cells. Hematology Reports, 13(4), 9215. https://doi.org/10.4081/hr.2021.9215

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