Erythroid Krüppel Like Factor (EKLF) Gene Expression in β-thalassemia Patients

β-thalassemia is a common inherited disorder caused by absent or reduced synthesis of the hemoglobin subunit beta (beta globin chain) , it has 3 clinical types; minor which is a carrier state, intermedia and major which are differentiated by blood transfusion dependency and lab findings.

In β-thalassemia, insufficient production of the β-globin molecule results in an excess of free α-globin chains that can precipitate within erythroid precursors, impairing their maturation and leads to death of these precursors and ineffective production of erythroid cells. As a result, a significant anaemia occurs and the consequent expansion of erythroid precursors can lead to secondary problems in bones and other organs.

These mutations are primarily point mutations that affect transcriptional control, translation, and splicing of the beta haemoglobin gene and gene expression.

The frequency of beta-thalassemia mutations varies by regions of the world with the highest prevalence in the Mediterranean, the Middle East, and Southeast and Central Asia. Approximately 68000 children are born with beta-thalassemia. Its prevalence is 80-90 million carriers, around 1.5% of the global population.

Erythroid Krüppel-like factor (EKLF or KLF1) is a transcriptional regulator that plays a major role in lineage-restricted control of gene expression. KLF1 expression and activity are tightly controlled in a temporal and differentiation stage-specific manner. The mechanisms by which KLF1 is regulated encompass a range of biological processes, including control of KLF1 RNA transcription, protein stability, localization, and posttranslational modifications. Intact KLF1 regulation is essential to correctly regulate erythroid function by gene transcription and to maintain hematopoietic lineage homeostasis by ensuring a proper balance of erythroid/megakaryocytic differentiation. In turn, KLF1 regulates erythroid biology by a wide variety of mechanisms, including gene activation and repression by regulation of chromatin configuration, transcriptional initiation and elongation, and localization of gene loci to transcription factories in the nucleus.