TY - JOUR
T1 - KLF10 gene expression is associated with high fetal hemoglobin levels and with response to hydroxyurea treatment in β-hemoglobinopathy patients
AU - Borg, Joseph
AU - Phylactides, Marios
AU - Bartsakoulia, Marina
AU - Tafrali, Christina
AU - Lederer, Carsten
AU - Felice, Alexander E.
AU - Papachatzopoulou, Adamantia
AU - Kourakli, Alexandra
AU - Stavrou, Eleana F.
AU - Christou, Soteroula
AU - Hou, Jun
AU - Karkabouna, Sophia
AU - Lappa-Manakou, Christina
AU - Ozgur, Zeliha
AU - van Ijcken, Wilfred
AU - von Lindern, Marieke
AU - Grosveld, Frank G.
AU - Georgitsi, Marianthi
AU - Kleanthous, Marina
AU - Philipsen, Sjaak
AU - Patrinos, George P.
PY - 2012
Y1 - 2012
N2 - 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
AB - 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
U2 - https://doi.org/10.2217/PGS.12.125
DO - https://doi.org/10.2217/PGS.12.125
M3 - Article
C2 - 23057549
SN - 1462-2416
VL - 13
SP - 1487
EP - 1500
JO - Pharmacogenomics
JF - Pharmacogenomics
IS - 13
ER -