JAK1, 2, 3 and STAT1, 3, 5, 6 are activated in response to BCR–ABL1 signaling in p190 transduced cells, JAK2 also directly phosphorylates BCR–ABL1. JAK2 knockdown and dual JAK2/BCR–ABL1 inhibition impairs CML cell lines in vitro and in xenografts, and CML cells in vitro (52, 249). This evidence concerns the gene BCR and chronic myelogenous leukemia, BCR-ABL1 positive.