KLF10 gene expression is associated with high fetal hemoglobin levels and with response to hydroxyurea treatment in β-hemoglobinopathy patients. (October 2012)

• Record Type: Journal Article
• Authors: Borg, Joseph; Phylactides, Marios; Bartsakoulia, Marina; Tafrali, Christina; Lederer, Carsten; Felice, Alexander E; Papachatzopoulou, Adamantia; Kourakli, Alexandra; Stavrou, Eleana F; Christou, Soteroula; Hou, Jun; Karkabouna, Sophia; Lappa-Manakou, Christina; Özgur, Zeliha; van IJcken, Wilfred; von Lindern, Marieke; Grosveld, Frank G; Georgitsi, Marianthi; Kleanthous, Marina; Philipsen, Sjaak; Patrinos, George P
• Is Part Of: Pharmacogenomics. Volume 13:Number 13(2012)
• Page Start: 1487
• Page End: 1500
• Publication Date: 2012-10
• Subjects: β-thalassemia -- hydroxyurea -- KLF10 -- pharmacogenomics -- sickle cell disease -- transcription profiling; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.12.125
• Languages: English
• ISSNs: 1462-2416

Abstract

Aim: In humans, fetal hemoglobin (HbF) production is controlled by many intricate mechanisms that, to date, remain only partly understood.Patients & methods: Pharmacogenomic analysis of the effects of hydroxyurea (HU) on HbF production was undertaken in a collection of Hellenic βthalassemia and sickle cell disease (SCD) compound heterozygotes and a collection of healthy and KLF1 -haploinsufficient Maltese adults, to identify genomic signatures that follow high HbF patterns.Results: KLF10 emerged as a top candidate. Moreover, genotype analysis of βthalassemia major and intermedia patients and an independent cohort of βthalassemia/SCD compound heterozygous patients that do or do not respond to HU treatment showed that the homozygous mutant state of a tagSNP in the KLF10 3'UTR is not present in βthalassemia intermedia patients and is underrepresented in βthalassemia/SCD compound heterozygous patients that respond well to HU treatment.Conclusion: These data suggest that KLF10 may constitute a pharmacogenomic marker to discriminate between response and nonresponse to HU treatment. Original submitted: 2 May 2012; Revision submitted: 17 July 2012