Oncogene Addiction in Chronic Myeloid Leukaemia

Oncogene addiction is the dependence seen in some types of cancer cells on the presence or activity of an oncogene. Chronic myeloid leukaemia (CML) is driven by the BCR-ABL1 oncogene. CML has become a paradigm for targeted therapies, as the disease is effectively managed in most patients by BCR-ABL1 inhibitors. Although the symptom-causing leukaemic progenitor cells depend on the kinase activity of BCR-ABL1 for survival, the more primitive leukaemia stem cells (LSCs) responsible for disease maintenance and relapse are not dependent on the BCR-ABL1 oncogene and lie dormant in the bone marrow of patients during treatment. The advances in knowledge achieved through the study of CML LSCs indicate that cancer stem cells (CSCs), which underlie many different cancers, may not display oncogene addiction in the classical sense. This provides yet another obstacle to the efforts to cure cancers using targeted therapies. To eradicate these CSCs and discover ways to truly cure CML and other CSC-driven cancers, we must investigate them for their unique dependencies.