Pinyaphat KhamphikhamOrapan SripichaiThongperm MunkongdeeSuthat FucharoenSissades TongsimaDuncan R. SmithMahidol UniversityThailand National Center for Genetic Engineering and Biotechnology2019-08-282019-08-282018-03-01International Journal of Hematology. Vol.107, No.3 (2018), 297-31018653774092557102-s2.0-85031995292https://repository.li.mahidol.ac.th/handle/123456789/46895© 2017, The Japanese Society of Hematology. Heterogeneity of HbF levels in β0-thalassemia/HbE disease has been reported to be associated with variations in clinical manifestations of the disease, and several genetic-modifying factors beyond the β-globin gene cluster have been identified as HbF regulators. Down-regulation or heterozygous mutations of Krüppel-like factor 1 (KLF1) is associated with elevated HbF levels in non-thalassemia subjects. This study confirms that experimental down-regulation of KLF1 in β0-thalassemia/HbE-derived erythroblasts significantly increases HbF production (up to 52.3 ± 2.4%), albeit with slightly delayed erythroid terminal differentiation. KLF1 exome sequencing of 130 Thai β0-thalassemia/HbE patients without co-inheritance of α-thalassemia found six patients with KLF1 heterozygous mutations including rs2072596 (p.F182L; n = 5) and rs745347362 (p.P284L; n = 1) missense mutations. However, while these patients had high HbF levels (38.1 ± 7.5%), they were all associated with a severe clinical phenotype. These results suggest that while reduction of KLF1 expression in β0-thalassemia/HbE erythroblasts can increase HbF levels, it is not sufficient to alleviate the clinical phenotype.Mahidol UniversityMedicineArticleSCOPUS10.1007/s12185-017-2357-3