While this suggests that PI3K is important to LSC-extrinsic means of TKI resistance, other evidence has shown that CML cell intrinsic BCR::ABL1 signalling via the PI3K/AKT/mTOR axis also drives TKI resistance/cell survival, via other players including epidermal growth factor receptor kinase substrate 8 (EPS8) [90] and c-Myc [91]. This evidence concerns the gene EPS8 and chronic myelogenous leukemia, BCR-ABL1 positive.