KLF1 (Krüppel-like factor 1) variants in the pathogenesis of hematological diseases

Abstract

KLF1 (Krüppel-like factor 1) is an erythroid transcription factor involved in various stages of red blood cell formation. KLF1 plays key functions at the megakaryocyte-erythrocyte progenitor stage, where it is involved in the development of the erythrocyte lineage. It participates in the global expression of erythrocyte genes, playing a direct role in globin switching. KLF1 also participates in the final maturation of erythrocytes, controlling exit from the cell cycle and the enucleation process. KLF1 has a domain structure: N-terminal transactivation domain and C-terminal DNA-binding domain. Many variants (mutations) have been described in the KLF1 gene, which lead to the development of a whole spectrum of phenotypes: from clinically insignificant morphological changes, through mild changes, to severe pathological conditions. Two mutations are dominant. One occurs in mice and causes neonatal anemia with congenital spherocytosis (Nan), the other in humans and leads to congenital dyserythropoietic anemia type IV (CDA).