FLT3 is a receptor tyrosine kinase expressed on hematopoietic progenitor cells and dendritic cells that regulates their differentiation, proliferation, and survival upon binding FLT3 ligand 1. Wild-type FLT3 activates multiple downstream signaling cascades including PI3K/AKT, RAS/MAPK, and STAT5 pathways 2. FLT3 mutations occur in 25-30% of acute myeloid leukemia (AML) cases and represent one of the most frequent genetic alterations 3. The most common mutations are internal tandem duplications (FLT3-ITD) and tyrosine kinase domain point mutations (FLT3-TKD), both associated with poor prognosis 3. FLT3-ITD mutations cause constitutive kinase activation and promote cell survival while promoting resistance to apoptosis 2. Notably, FLT3-ITD localization and signaling are regulated by S-palmitoylation; disruption of this modification increases surface expression and enhances leukemic progression 2. Recent studies demonstrate that FLT3 is genetically essential specifically for ITD-mutated leukemic stem cells but dispensable for normal hematopoietic stem cells, supporting FLT3 as an ideal therapeutic target 4. Clinical FLT3-targeting strategies include tyrosine kinase inhibitors and emerging approaches targeting downstream effectors like RSK1 5.