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 cultur...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Hematology Reports |
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| Online Access: | https://www.pagepress.org/journals/index.php/hr/article/view/9215 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-10T18:38:02Z |
| format | Article |
| id | doaj.art-f4f7685b6a5e43a99dd8c5878570edf6 |
| institution | Directory Open Access Journal |
| issn | 2038-8322 2038-8330 |
| language | English |
| last_indexed | 2024-04-10T18:38:02Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Hematology Reports |
| spelling | doaj.art-f4f7685b6a5e43a99dd8c5878570edf62023-02-02T00:45:53ZengMDPI AGHematology Reports2038-83222038-83302021-11-0113410.4081/hr.2021.9215LSD1 inhibition enhances robust fetal hemoglobin induction in human β0-thalassemia/HbE erythroid cellsOrapan Sripichai0Woratree KaewsakulthongPhitchapa PongpaksupasinTiwaporn NualkaewSuradej HongengSuthat FucharoenNatee JearawiriyapaisarnNational Institute of HealthInduction 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.https://www.pagepress.org/journals/index.php/hr/article/view/9215thalassemia, erythroid, fetal hemoglobin, LSD1, RN-1 |
| spellingShingle | 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 Hematology Reports thalassemia, erythroid, fetal hemoglobin, LSD1, RN-1 |
| title | 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_short | 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 |
| topic | thalassemia, erythroid, fetal hemoglobin, LSD1, RN-1 |
| url | https://www.pagepress.org/journals/index.php/hr/article/view/9215 |
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