Biologie moléculaire de la leucémie myéloïde chronique : dernières avancées

Chronic Myeloid Leukemia (CML) is a well-known model of oncogenesis. Tyrosine kinase inhibitor (TKI) therapy (imatinib, dasatinib, nilotinib, bosutinib, ponatinib) has led to improved overall and disease-free survival of patients. The molecular monitoring, based on the quantification of BCR-ABL1 mRNA by RQ-PCR and the mutation analysis of the ABL tyrosine kinase domain, assess drug effectiveness. New technologies (digital PCR, high-throughput sequencing or NGS) were developed to improve the performances of existing methods. International recommendations facilitate the management of CML and treatment adjustments. Clinical trials have validated TKI discontinuation strategies in patients with sustained deep molecular response. In nearly 50% of patients, BCR-ABL1 mRNA is never detected after treatment cessation. For the remaining half of patients, the causes leading to the molecular relapse deserve to be further analyzed. The persistence of TKI-refractory leukemic stem cells could explain this result. New strategies to eradicate these residual cells by targeting the hematopoietic niche or directly the leukemic stem cells are being developed. Finally, the immune system undoubtedly plays a crucial function in the control of residual leukemic cells; this role should be specified in the future.