One major mechanism of resistance in CML independent of BCR-ABL kinase domain mutations is the activation of alternate signaling pathways.[5,6] For example, mitogen-activated protein kinase (MAPK)/Protein Kinase C (PKC) pathway activation has been identified as a major driver of BCR-ABL mutation-independent imatinib resistance.[7] Imatinib alone is inherently incapable of rendering deep molecular responses in these cases. The gene discussed is BCR; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.