A systematic review of known mechanisms of hydroxyurea-induced fetal hemoglobin for treatment of sickle cell disease

Expert Review of Hematology
Gift D PuleAmbroise Wonkam

Abstract

To report on molecular mechanisms of fetal hemoglobin (HbF) induction by hydroxyurea (HU) for the treatment of sickle cell disease. Systematic review. Studies have provided consistent associations between genomic variations in HbF-promoting loci and variable HbF level in response to HU. Numerous signal transduction pathways have been implicated, through the identification of key genomic variants in BCL11A, HBS1L-MYB, SAR1 or XmnI polymorphism that predispose the response to the treatment, and signal transduction pathways that modulate γ-globin expression (cAMP/cGMP; Giα/c-Jun N-terminal kinase/Jun; methylation and miRNA). Three main molecular pathways have been reported: i) Epigenetic modifications, transcriptional events and signaling pathways involved in HU-mediated response, ii) Signaling pathways involving HU-mediated response and iii) Post-transcriptional pathways (regulation by miRNAs). The complete picture of HU-mediated mechanisms of HbF production in Sickle Cell Disease remains elusive. Research on post-transcriptional mechanisms could lead to therapeutic targets that may minimize alterations to the cellular transcriptome.

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Citations

Sep 17, 2016·Omics : a Journal of Integrative Biology·Khuthala MnikaAmbroise Wonkam
Oct 25, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·Michael TarasevSumita Chakraborty
Jul 4, 2017·The Cochrane Database of Systematic Reviews·Noemi Ba RoyLise J Estcourt
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May 14, 2017·The Cochrane Database of Systematic Reviews·Lise J EstcourtMiguel R Abboud
Sep 13, 2018·The Pharmacogenomics Journal·Sètondji Cocou Modeste Alexandre YahouédéhouMarilda de Souza Gonçalves
Jun 25, 2019·Frontiers in Genetics·Khuthala MnikaAmbroise Wonkam
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Jul 21, 2021·International Journal of Molecular Sciences·Filomena LongoAntonio Piga

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