After more than a decade of clinical experience, TKI have demonstrated two main limits: first, about 15% of patients with chronic phase CML and virtually all patients with BCR-ABL+ ALL exhibit primary or acquired resistance to imatinib (i.e. they fail to maintain long-term cytogenetic and/or molecular remission); second and perhaps more important, TKI do not eradicate the leukemic stem cell pool even in patients who have an optimal response to TKI, as demonstrated by molecular relapse in the majority of patient who discontinue therapy [3]. This evidence concerns the gene ABL1 and chronic myelogenous leukemia, BCR-ABL1 positive.