PKM2 overexpression is associated with imatinib resistance in CML cell lines and gefitinib resistance in colorectal cancer.279,280 In addition to inducing lactate production, PKM2 can directly activate the PI3K/AKT pathway and STAT3-related pathway to develop drug resistance. This evidence concerns the gene AKT1 and chronic myelogenous leukemia, BCR-ABL1 positive.