Moreover, FLT3-independent activation ofRAS/MAPK and/or PI3K/AKT/mTOR signaling pathways, along with the sustainedexpression of genes involved in FLT3-mediated cellular transformation, has beenobserved in FLT3 inhibitor-resistant cell lines and primary samples (37,38).Additionally, non-genetic mechanisms, such as soluble factors from the bone marrowmicroenvironment, can activate the downstream RAS/MAPK, PI3K/AKT, and mTOR signalingin AML cells, contributing to early treatment resistance against FLT3 inhibitors(39–41). The gene discussed is FLT3; the disease is acute myeloid leukemia.