Indeed, treatment with imatinib or second-generation tyrosine-kinase inhibitors (TKIs) has markedly improved the survival of CML patients; however, individual intolerance to these inhibitors, the emergence of clones with TKI-resistant BCR-ABL mutations, and the observation that leukemia-initiating/stem cells are intrinsically resistant to these drugs, in part due to overacting PI3K/AKT/mTOR and β-catenin pathways, support the ongoing search for new drugs targeting CML stem cells [14,15]. The gene discussed is ABL1; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.