Publication: Genetic variation of Krüppel-like factor 1 (KLF1) and fetal hemoglobin (HbF) levels in β<sup>0</sup>-thalassemia/HbE disease
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Issued Date
2018-03-01
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18653774
09255710
09255710
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2-s2.0-85031995292
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Mahidol University
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SCOPUS
Bibliographic Citation
International Journal of Hematology. Vol.107, No.3 (2018), 297-310
Suggested Citation
Pinyaphat Khamphikham, Orapan Sripichai, Thongperm Munkongdee, Suthat Fucharoen, Sissades Tongsima, Duncan R. Smith Genetic variation of Krüppel-like factor 1 (KLF1) and fetal hemoglobin (HbF) levels in β<sup>0</sup>-thalassemia/HbE disease. International Journal of Hematology. Vol.107, No.3 (2018), 297-310. doi:10.1007/s12185-017-2357-3 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/46895
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Title
Genetic variation of Krüppel-like factor 1 (KLF1) and fetal hemoglobin (HbF) levels in β<sup>0</sup>-thalassemia/HbE disease
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Abstract
© 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.