Germline Single-Nucleotide Polymorphism <i>GFI1-36N</i> Causes Alterations in Mitochondrial Metabolism and Leads to Increased ROS-Mediated DNA Damage in a Murine Model of Human Acute Myeloid Leukemia.

ABSTRACT: Background/Objectives: GFI1-36N represents a single-nucleotide polymorphism (SNP) of the zinc finger protein Growth Factor Independence 1 (GFI1), in which the amino acid serine (S) is replaced by asparagine (N). The presence of the GFI1-36N gene variant is associated with a reduced DNA repair capacity favoring myeloid leukemogenesis and leads to an inferior prognosis of acute myeloid leukemia (AML) patients. However, the underlying reasons for the reduced DNA repair capacity in GFI1-36N leukemic cells are largely unknown. Since we have demonstrated that GFI1 plays an active role in metabolism, in this study, we investigated whether increased levels of reactive oxygen species (ROS) could contribute to the accumulation of genetic damage in GFI1-36N leukemic cells.

SUBMITTER: Vorwerk J 

PROVIDER: S-EPMC11762481 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature