Stem cell persistence in chronic myeloid leukemia

Tyrosine kinase inhibitors (TKIs) of BCR-ABL have turned chronic myeloid leukemia (CML) from a deadly disease into a chronic ailment. Unfortunately, evidence is accumulating that TKIs are not curative, since CML stem cells are not addicted to BCR-ABL, and persist despite TKI therapy. On closer view this is not surprising, as it reflects fundamental principles of CML pathogenesis. Strategies to eradicate CML stem cells will most likely be based on synthetic lethality though parallel inhibition of BCR-ABL and other critical pathways.