International Journal of Hematology

, Volume 107, Issue 3, pp 297–310 | Cite as

Genetic variation of Krüppel-like factor 1 (KLF1) and fetal hemoglobin (HbF) levels in β0-thalassemia/HbE disease

  • Pinyaphat Khamphikham
  • Orapan Sripichai
  • Thongperm Munkongdee
  • Suthat Fucharoen
  • Sissades Tongsima
  • Duncan R. Smith
Original Article


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.


Krüppel-like factor 1 KLF1 β-Thalassemia Hemoglobin E Hemoglobin F 



This work was supported by grants from Mahidol University and by a National Science and Technology Development Agency (NSTDA) Research Chair Grant. PK is supported by a Thailand Graduate Institute of Science and Technology (TGIST) scholarship (TG-22-14-58-037D) from the National Science and Technology Development Agency (NSTDA), Thailand. We sincerely thank all donors who participated in this study.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest.

Supplementary material

12185_2017_2357_MOESM1_ESM.pdf (1.1 mb)
Supplementary material 1 (PDF 1148 kb)


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Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  1. 1.Institute of Molecular BiosciencesMahidol UniversitySalayaThailand
  2. 2.National Center for Genetic Engineering and Biotechnology, National Science and Technology Development AgencyPathum ThaniThailand

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