KLF10 Gene Expression is Associated with High Fetal Hemoglobin Levels and with Response to Hydroxyurea Treatment in β-Hemoglobinopathy Patients

• DOI: 10.2217/pgs.12.125
• Publication Date: 2012-10-12T10:32:03Z
• Authors: Joseph Borg; Marios Phylactides; Marina Bartsakoulia; Christina Tafrali; Carsten Lederer; Alexander E Felice; Adamantia Papacha...; Alexandra Kourakli; Eleana F Stavrou; Soteroula Christou; Jun Hou; Sophia Karkabouna; Christina Lappa-M...; Zeliha Özgur; Wilfred van IJcken; Marieke von Lindern; Frank G Grosveld; Marianthi Georgitsi; Marina Kleanthous; Sjaak Philipsen; George P Patrinos
• Keywords: Hemoglobinopathy; Compound heterozygosity; Pharmacogenomics

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 hydroxyurea (HU) on HbF was undertaken in a collection Hellenic βthalassemia and sickle cell disease (SCD) compound heterozygotes healthy KLF1-haploinsufficient Maltese adults, identify genomic signatures that follow high patterns. Results: KLF10 emerged as top candidate. Moreover, genotype major intermedia patients an independent cohort βthalassemia/SCD heterozygous do or not respond HU treatment showed homozygous mutant state tagSNP 3'UTR present underrepresented well treatment. Conclusion: These data suggest may constitute pharmacogenomic marker discriminate between response nonresponse Original submitted: 2 May 2012; Revision 17 July 2012