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 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. RESULTS: 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. CONCLUSION: These data suggest that KLF10 may constitute a pharmacogenomic marker to discriminate between response and nonresponse to HU treatment.
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 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. RESULTS: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. CONCLUSION: These data suggest that KLF10 may constitute a pharmacogenomic marker to discriminate between response and nonresponse to HU treatment.
Authors: Deepika S Darbari; Johnson P Hampson; Eric Ichesco; Nadja Kadom; Gilbert Vezina; Iordanis Evangelou; Daniel J Clauw; James G Taylor Vi; Richard E Harris Journal: J Pain Date: 2015-08-18 Impact factor: 5.820
Authors: Serena Sclafani; Alice Pecoraro; Veronica Agrigento; Antonio Troia; Rosario Di Maggio; Massimiliano Sacco; Aurelio Maggio; Elena D'Alcamo; Rosalba Di Marzo Journal: Hematol Rep Date: 2016-12-09
Authors: Kariofyllis Karamperis; Maria T Tsoumpeli; Fotios Kounelis; Maria Koromina; Christina Mitropoulou; Catia Moutinho; George P Patrinos Journal: Hum Genomics Date: 2021-06-05 Impact factor: 4.639