Growth factor independence 1 (GFI1) is a DNA-binding zinc finger protein that acts as a transcriptional repressor [1]. 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 can recruit histone-modifying enzymes to target genes, thereby regulating gene expression [1]. It is also involved in the development of hair cells in the inner ear, regulating the expression of hair-cell-related genes [2].

In the context of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), GFI1 has been shown to be involved in their pathogenesis. For example, GFI1 expression levels correlate with patient survival and treatment response in both AML and MDS [1]. A non-synonymous single nucleotide polymorphism (SNP) of GFI1, GFI1-36N, is a prognostic factor for the development of AML and MDS. GFI1-36N leads to genome-wide epigenetic changes at GFI1-occupied target gene promoters and enhancers, and affects 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 related pathways can cause synthetic lethality in AML samples expressing GFI1-36N [3].

In conclusion, GFI1 is a key regulator in hematopoiesis and inner-ear development. In diseases like AML and MDS, studies on GFI1, especially through analysis of genetic variants like GFI1-36N, have provided insights into disease pathogenesis and potential therapeutic strategies. Understanding GFI1's functions helps in exploring new treatment options for hematological malignancies.