LSD1 inhibition enhances robust fetal hemoglobin induction in human β0-thalassemia/HbE erythroid cells

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 cultu...

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Autores principales:	Orapan Sripichai, Woratree Kaewsakulthong, Phitchapa Pongpaksupasin, Tiwaporn Nualkaew, Suradej Hongeng, Suthat Fucharoen, Natee Jearawiriyapaisarn
Formato:	article
Lenguaje:	EN
Publicado:	PAGEPress Publications 2021
Materias:	thalassemia, erythroid, fetal hemoglobin, LSD1, RN-1 Diseases of the blood and blood-forming organs RC633-647.5
Acceso en línea:	https://doaj.org/article/f4f7685b6a5e43a99dd8c5878570edf6
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spelling	oai:doaj.org-article:f4f7685b6a5e43a99dd8c5878570edf62021-11-26T14:38:40ZLSD1 inhibition enhances robust fetal hemoglobin induction in human β0-thalassemia/HbE erythroid cells10.4081/hr.2021.92152038-83222038-8330https://doaj.org/article/f4f7685b6a5e43a99dd8c5878570edf62021-11-01T00:00:00Zhttps://www.pagepress.org/journals/index.php/hr/article/view/9215https://doaj.org/toc/2038-8322https://doaj.org/toc/2038-8330 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. Orapan SripichaiWoratree KaewsakulthongPhitchapa PongpaksupasinTiwaporn NualkaewSuradej HongengSuthat FucharoenNatee JearawiriyapaisarnPAGEPress Publicationsarticlethalassemia, erythroid, fetal hemoglobin, LSD1, RN-1Diseases of the blood and blood-forming organsRC633-647.5ENHematology Reports, Vol 13, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	thalassemia, erythroid, fetal hemoglobin, LSD1, RN-1 Diseases of the blood and blood-forming organs RC633-647.5
spellingShingle	thalassemia, erythroid, fetal hemoglobin, LSD1, RN-1 Diseases of the blood and blood-forming organs RC633-647.5 Orapan Sripichai Woratree Kaewsakulthong Phitchapa Pongpaksupasin Tiwaporn Nualkaew Suradej Hongeng Suthat Fucharoen Natee Jearawiriyapaisarn LSD1 inhibition enhances robust fetal hemoglobin induction in human β0-thalassemia/HbE erythroid cells
description	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.
format	article
author	Orapan Sripichai Woratree Kaewsakulthong Phitchapa Pongpaksupasin Tiwaporn Nualkaew Suradej Hongeng Suthat Fucharoen Natee Jearawiriyapaisarn
author_facet	Orapan Sripichai Woratree Kaewsakulthong Phitchapa Pongpaksupasin Tiwaporn Nualkaew Suradej Hongeng Suthat Fucharoen Natee Jearawiriyapaisarn
author_sort	Orapan Sripichai
title	LSD1 inhibition enhances robust fetal hemoglobin induction in human β0-thalassemia/HbE erythroid cells
title_short	LSD1 inhibition enhances robust fetal hemoglobin induction in human β0-thalassemia/HbE erythroid cells
title_full	LSD1 inhibition enhances robust fetal hemoglobin induction in human β0-thalassemia/HbE erythroid cells
title_fullStr	LSD1 inhibition enhances robust fetal hemoglobin induction in human β0-thalassemia/HbE erythroid cells
title_full_unstemmed	LSD1 inhibition enhances robust fetal hemoglobin induction in human β0-thalassemia/HbE erythroid cells
title_sort	lsd1 inhibition enhances robust fetal hemoglobin induction in human β0-thalassemia/hbe erythroid cells
publisher	PAGEPress Publications
publishDate	2021
url	https://doaj.org/article/f4f7685b6a5e43a99dd8c5878570edf6
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LSD1 inhibition enhances robust fetal hemoglobin induction in human β0-thalassemia/HbE erythroid cells

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