TY - JOUR T1 - ABL1-Directed Inhibitors for CML: Efficacy, Resistance and Future Perspectives JF - Anticancer Research JO - Anticancer Res SP - 2457 LP - 2465 DO - 10.21873/anticanres.14215 VL - 40 IS - 5 AU - MICHELE MASSIMINO AU - STEFANIA STELLA AU - ELENA TIRRĂ’ AU - MARIA STELLA PENNISI AU - SILVIA RITA VITALE AU - ADRIANA PUMA AU - CHIARA ROMANO AU - SANDRA DI GREGORIO AU - CRISTINA TOMARCHIO AU - FRANCESCO DI RAIMONDO AU - LIVIA MANZELLA Y1 - 2020/05/01 UR - http://ar.iiarjournals.org/content/40/5/2457.abstract N2 - The introduction of tyrosine kinase inhibitors (TKIs) directed against the catalytic activity of the ABL tyrosine kinase has considerably improved the outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease. Indeed, these individuals currently show a life-expectancy comparable to those of healthy subjects. Currently, five TKIs (imatinib, dasatinib, nilotinib, bosutinib and ponatinib) are approved for the treatment of CML and can be used as first, second or further lines of treatment according to disease risk scores, patient comorbidities and the presence of known TKI resistance mechanisms. In fact, 15-20% of all CML patients fail to achieve optimal responses according to the current definitions of the European Leukemia Network and will require sequential TKI treatment to avoid disease progression. In this review, we present the state of art in several crucial areas of CML management by briefly: i) depicting the domain structure of the BCR-ABL1 oncoprotein; ii) describing pivotal data concerning TKI efficacy; iii) illustrating the diverse molecular mechanisms causing TKI resistance; and iv) summarizing new ABL1-directed therapeutic approaches that are presently under investigation. ER -