Contribution of Chronic Myeloid Leukaemia (CML) as a Disease Model to Define and Study Clonal Heterogeneity

Although tumour cell intra-clonal heterogeneity has been known for many years, its application in the oncology clinical practice (patient management, prognosis, etc.) remains limited. For this, chronic myeloid leukaemia (CML) is a remarkable model. Basic research studies revealed the heterogeneity of the initial clone, and led to the hypothesis of the existence of leukemic stem cells. Nevertheless, the indisputable evidence of the intra-clonal heterogeneity role in the therapeutic response came from the outcomes of the treatment with tyrosine kinase inhibitors (the first targeted therapy in medicine) combined with the early and rigorous clinical and molecular monitoring of these patients. CML management already takes this heterogeneity into account for personalized patient follow-up. The adventure continues with the objectives of better tailoring the treatment and of curing the disease in most of the patients.