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


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 ?-globin expression (cAMP/cGMP; Gi?/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.

SUBMITTER: Pule GD 

PROVIDER: S-EPMC4829639 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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

Pule Gift D GD   Mowla Shaheen S   Novitzky Nicolas N   Wiysonge Charles S CS   Wonkam Ambroise A  

Expert review of hematology 20150901 5


<h4>Aim</h4>To report on molecular mechanisms of fetal hemoglobin (HbF) induction by hydroxyurea (HU) for the treatment of sickle cell disease.<h4>Study design</h4>Systematic review.<h4>Results</h4>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 p  ...[more]

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