Resumen
Tyrosine kinase inhibitors (TKIs), such as imatinib, have become the standard initial treatment of choice for chronic myeloid leukemia (CML) patients. However, one obstacle to face is that a significant proportion of patients presents poor response to TKIs, or acquires resistance resulting in disease relapses. Mutations in BCR-ABL1 protein are a well described mechanism of resistance but other not well established mechanisms outside BCR-ABL1 mutations are emerging as important in the acquisition of resistance. Abnormal metabolism of CML cells that acquire resistance to imatinib has been pointed out as a putative downstream key event, but deep studies aimed to unveil metabolic adaptations associated with acquired resistance are still lacking. Here, we perform an exhaustive study on metabolic reprogramming associated with acquired imatinib resistance and we identify metabolic vulnerabilities of CML imatinib resistant cells that could pave the way for new therapies targeting TKI failure.