Activation of RAF/mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK) signaling pathway in a RAS-dependent manner plays an important part in BCR-ABL-independent TKI resistance through an increase in the expression of protein kinase C (PKC) and protein kinase C eta (PRKCH), leading to additional proliferation along with the inhibition of CML stem cells apoptosis by the activation of transcription factors including c-JUN, c-MYC, and c-FOS, as well as the expression of genes involved in proliferation processes [17, 112]. Here, WNK2 is linked to chronic myelogenous leukemia, BCR-ABL1 positive.