Growth factor independence 1 (GFI1) is a DNA-binding zinc finger protein that acts as a transcriptional repressor [1,3,5]. It plays crucial roles in hematopoiesis, regulating the function of hematopoietic stem-and precursor cells, as well as differentiation along myeloid and lymphoid lineages [1]. GFI1 mediates transcriptional repression mainly by recruiting histone-modifying enzymes to its target genes, thus participating in epigenetic regulation [1].

In acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), GFI1 has been implicated in pathogenesis. For instance, its expression levels correlate with patient survival and treatment response in both diseases, and can influence disease progression in experimental animal models [1]. A non-synonymous single nucleotide polymorphism (SNP), GFI1-36N, is a prognostic factor for AML and MDS development. This variant leads to genome-wide epigenetic changes at GFI1-occupied target gene promoters and enhancers, affecting the response of leukemic cells to epigenetic drugs [1]. In addition, GFI1-36N expression is associated with increased chromosomal aberrations, mutational burden, and impaired homologous recombination-directed DNA repair in leukemic cells. Targeting DNA repair-related proteins in GFI1-36N-expressing AML cells shows promise for treatment [4].

In the inner ear, Gfi1 is important for hair cell (HC) development, regulating HC-related gene expression. Ectopic expression of Gfi1 in supporting cells can potentially regenerate HCs [2].

In conclusion, GFI1 is a key regulator in hematopoiesis and inner ear development. Its role in diseases like AML and MDS is significant, especially in relation to epigenetic regulation and DNA repair. The study of GFI1, particularly through genetic models such as mouse models with GFI1-related mutations, provides valuable insights into its functions and potential therapeutic applications in hematological diseases and inner ear regeneration.