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

摘要

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 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. Results: KLF10 emerged as a top candidate. Moreover, genotype analysis of thalassemia major and intermedia patients and an independent cohort of 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 3UTR is not present in thalassemia intermedia patients and is underrepresented in thalassemia/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 201.