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

Joseph Borg, Marios Phylactides, Marina Bartsakoulia, Christina Tafrali, Carsten Lederer, Alexander E. Felice, Adamantia Papachatzopoulou, Alexandra Kourakli, Eleana F. Stavrou, Soteroula Christou, Jun Hou, Sophia Karkabouna, Christina Lappa-Manakou, Zeliha Ozgur, Wilfred van Ijcken, Marieke von Lindern, Frank G. Grosveld, Marianthi Georgitsi, Marina Kleanthous, Sjaak PhilipsenGeorge P. Patrinos

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In humans, fetal hemoglobin (HbF) production is controlled by many intricate mechanisms that, to date, remain only partly understood. Pharmacogenomic analysis of the effects of hydroxyurea (HU) on HbF production was undertaken in a collection of Hellenic β-thalassemia 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. KLF10 emerged as a top candidate. Moreover, genotype analysis of β-thalassemia major and intermedia patients and an independent cohort of β-thalassemia/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 β-thalassemia intermedia patients and is underrepresented in β-thalassemia/SCD compound heterozygous patients that respond well to HU treatment. These data suggest that KLF10 may constitute a pharmacogenomic marker to discriminate between response and nonresponse to HU treatment
Original languageEnglish
Pages (from-to)1487-1500
Issue number13
Publication statusPublished - 2012

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