MLF1 (myeloid leukemia factor 1) is a transcriptional regulator with distinct roles in hematopoietic differentiation and disease pathogenesis. In normal hematopoiesis, MLF1 restricts erythroid formation while enhancing myeloid lineage commitment by suppressing erythropoietin-induced differentiation through p27Kip1 downregulation 1. MLF1 functions as a transcription factor that binds DNA and recruits co-activators; recent evidence demonstrates it recruits the acetyltransferase EP300 to promote H3K27ac deposition at target promoters, facilitating chr3 opening at senescence-associated genes 2. In disease contexts, MLF1 deregulation drives malignant progression. The NPM-MLF1 fusion protein, arising from t(3;5) translocations in acute myeloid leukemia and myelodysplastic syndromes, shows aberrant nuclear/nucleolar localization and interacts with chr3 remodeling complexes (ISWI, NuRD, P/BAF) to dysregulate hematopoietic gene expression 134. In intrahepatic cholangiocarcinoma, MLF1 upregulation—driven by miR-29c-3p downregulation via promoter hypermethylation—promotes tumor progression through EGFR/AKT and Wnt/β-catenin pathway activation 5. Clinically, elevated MLF1 expression correlates with worse prognosis in cholangiocarcinoma patients, and miR-29c-3p restoration shows therapeutic potential 5. XPO1 inhibition suppresses NPM1-MLF1-driven leukemogenesis 4, suggesting targeted therapeutic strategies.