P039 | Targeting oncogene-induced senescence in ETV6::RUNX1 pre-leukemic cells

Introduction: The t(12;21)(p13;q22) is the most common chromosomal translocation in pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL), occurring in 5% of healthy newborns. This alteration generates the ETV6::RUNX1 (E::R) fusion gene, encoding an aberrant transcription factor that is insufficient to cause leukemia directly, but establishes a clinically silent pre-leukemic progenitor not yet fully characterized. We previously showed that E::R expression in the murine pro-B BaF3 cells caused the slowdown of cell cycle progression and increased phospho-histone H2AX levels, both features of Oncogene Induced Senescence (OIS).Methods. We explored whether E::R induces OIS in immature hematopoietic cells to uncover therapeutic targets for pre-leukemia. We used two E::R+ pre-leukemic models: an inducible BaF3 Pro-B cell system and Sca1-E::R transgenic mice, where E::R is expressed in immature Lin−Sca1+ cells.Results. We observed that E::R caused a senescence-like phenotype in BaF3 cells, characterized by altered morphology, increased β-galactosidase activity (% SA β-Gal positive cells: ctr = 8.05 ± 10,61; E::R = 50.02 ± 9.95, p