Transcriptional regulators of fetal hemoglobin

Sickle cell anemia is a hereditary disease caused by sickle-shaped red blood cells that can lead to vaso-occlusive crises. Treatment options are currently limited, highlighting the need to develop new clinical approaches. Studies demonstrated that elevated levels of fetal hemoglobin (Hb F) are assoc...

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Main Authors: Gabriela Pereira dos Santos, Larissa Teodoro Rabi, André Alves Bezerra, Marcelo Rodrigues da Cunha, Amilton Iatecola, Victor Augusto Ramos Fernandes
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Hematology, Transfusion and Cell Therapy
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Online Access:http://www.sciencedirect.com/science/article/pii/S2531137924002967
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author Gabriela Pereira dos Santos
Larissa Teodoro Rabi
André Alves Bezerra
Marcelo Rodrigues da Cunha
Amilton Iatecola
Victor Augusto Ramos Fernandes
author_facet Gabriela Pereira dos Santos
Larissa Teodoro Rabi
André Alves Bezerra
Marcelo Rodrigues da Cunha
Amilton Iatecola
Victor Augusto Ramos Fernandes
author_sort Gabriela Pereira dos Santos
collection DOAJ
description Sickle cell anemia is a hereditary disease caused by sickle-shaped red blood cells that can lead to vaso-occlusive crises. Treatment options are currently limited, highlighting the need to develop new clinical approaches. Studies demonstrated that elevated levels of fetal hemoglobin (Hb F) are associated with a reduction of mortality and morbidity in sickle cell anemia patients. In light of this, researchers have been trying to elucidate the transcriptional regulation of Hb F to develop new therapeutic interventions. The present study aimed to present the main transcription factors of Hb F and discuss the clinical feasibility of these molecular targets. Two search strategies were used in the PubMed, SciELO, and LILACS databases between July and August 2023 to conduct this review. Manual searches were also conducted by checking references of potentially eligible studies. Eligibility criteria consisted of clinical trials and cohort studies from the last five years that investigated transcription factors associated with Hb F. The transcription factors investigated in at least four eligible studies were included in this review. As a result, 56 eligible studies provided data on the BCL11A, LRF, NF-Y, GATA1, KLF1, HRI, ATF4, and MYB factors. The studies demonstrated that Hb F is cooperatively regulated by transcription factors with the BCL11A factor appearing to be the most specific target gene for γ-globin induction. Although these data are promising, there are still significant gaps and intervention limitations due to the adverse functions of the target genes. New studies that clarify the aspects and functionalities of Hb F regulators may enable new clinical approaches for sickle cell anemia patients.
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spelling doaj-art-df49bf4325534eb89966e5597e58e25d2025-08-20T02:07:16ZengElsevierHematology, Transfusion and Cell Therapy2531-13792024-11-0146S258S26810.1016/j.htct.2024.06.001Transcriptional regulators of fetal hemoglobinGabriela Pereira dos Santos0Larissa Teodoro Rabi1André Alves Bezerra2Marcelo Rodrigues da Cunha3Amilton Iatecola4Victor Augusto Ramos Fernandes5Nossa Senhora do Patrocínio University Center, Itú, SP, BrazilNossa Senhora do Patrocínio University Center, Itú, SP, Brazil; Laboratory of Cancer Molecular Genetics, School of Medical Sciences (FCM), University of Campinas (UNICAMP), Campinas, SP, Brazil; Institute of Health Sciences, Paulista University (UNIP), Campinas, SP, BrazilNossa Senhora do Patrocínio University Center, Itú, SP, Brazil; College of Medicine of Jundiaí, Jundiaí, SP, BrazilNossa Senhora do Patrocínio University Center, Itú, SP, Brazil; College of Medicine of Jundiaí, Jundiaí, SP, BrazilNossa Senhora do Patrocínio University Center, Itú, SP, Brazil; College of Medicine of Jundiaí, Jundiaí, SP, BrazilNossa Senhora do Patrocínio University Center, Itú, SP, Brazil; College of Medicine of Jundiaí, Jundiaí, SP, Brazil; Corresponding author at: Jundiai Medicine College- Research Group (CNPq) in Neurobiology, Morphology and Pathology, Jundiaí, SP, Brazil.Sickle cell anemia is a hereditary disease caused by sickle-shaped red blood cells that can lead to vaso-occlusive crises. Treatment options are currently limited, highlighting the need to develop new clinical approaches. Studies demonstrated that elevated levels of fetal hemoglobin (Hb F) are associated with a reduction of mortality and morbidity in sickle cell anemia patients. In light of this, researchers have been trying to elucidate the transcriptional regulation of Hb F to develop new therapeutic interventions. The present study aimed to present the main transcription factors of Hb F and discuss the clinical feasibility of these molecular targets. Two search strategies were used in the PubMed, SciELO, and LILACS databases between July and August 2023 to conduct this review. Manual searches were also conducted by checking references of potentially eligible studies. Eligibility criteria consisted of clinical trials and cohort studies from the last five years that investigated transcription factors associated with Hb F. The transcription factors investigated in at least four eligible studies were included in this review. As a result, 56 eligible studies provided data on the BCL11A, LRF, NF-Y, GATA1, KLF1, HRI, ATF4, and MYB factors. The studies demonstrated that Hb F is cooperatively regulated by transcription factors with the BCL11A factor appearing to be the most specific target gene for γ-globin induction. Although these data are promising, there are still significant gaps and intervention limitations due to the adverse functions of the target genes. New studies that clarify the aspects and functionalities of Hb F regulators may enable new clinical approaches for sickle cell anemia patients.http://www.sciencedirect.com/science/article/pii/S2531137924002967Sickle cell anemiaFetal hemoglobinTranscription factorsGene therapyGamma-globin
spellingShingle Gabriela Pereira dos Santos
Larissa Teodoro Rabi
André Alves Bezerra
Marcelo Rodrigues da Cunha
Amilton Iatecola
Victor Augusto Ramos Fernandes
Transcriptional regulators of fetal hemoglobin
Hematology, Transfusion and Cell Therapy
Sickle cell anemia
Fetal hemoglobin
Transcription factors
Gene therapy
Gamma-globin
title Transcriptional regulators of fetal hemoglobin
title_full Transcriptional regulators of fetal hemoglobin
title_fullStr Transcriptional regulators of fetal hemoglobin
title_full_unstemmed Transcriptional regulators of fetal hemoglobin
title_short Transcriptional regulators of fetal hemoglobin
title_sort transcriptional regulators of fetal hemoglobin
topic Sickle cell anemia
Fetal hemoglobin
Transcription factors
Gene therapy
Gamma-globin
url http://www.sciencedirect.com/science/article/pii/S2531137924002967
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