Recent advances in understanding chronic myeloid leukemia: where do we stand?

While the need for complete eradication of leukemic stem cells (LSCs) in chronic myeloid leukemia may be controversial, it is agreed that remaining LSCs are the cause of relapse and disease progression. Current efforts are focused on the understanding of the persistence of immunophenotypically defined LSCs, which feature abnormalities in signaling pathways relating to autophagy, metabolism, epigenetics, and others and are influenced by leukemia cell-extrinsic factors such as the immune and bone marrow microenvironments. In sum, these elements modulate response and resistance to therapies and the clinical condition of treatment-free remission (TFR), the newly established goal in CML treatment, once the patient has achieved a durable molecular remission after treatment with tyrosine kinase inhibitors. Novel combination therapies based on these identified vulnerabilities of LSCs, aimed at the induction or maintenance of TFR, are being developed, while other research is directed at the elucidation of factors mediating progression to blast crisis.