RT Journal Article SR Electronic T1 ABL1-Directed Inhibitors for CML: Efficacy, Resistance and Future Perspectives JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2457 OP 2465 DO 10.21873/anticanres.14215 VO 40 IS 5 A1 MICHELE MASSIMINO A1 STEFANIA STELLA A1 ELENA TIRRĂ’ A1 MARIA STELLA PENNISI A1 SILVIA RITA VITALE A1 ADRIANA PUMA A1 CHIARA ROMANO A1 SANDRA DI GREGORIO A1 CRISTINA TOMARCHIO A1 FRANCESCO DI RAIMONDO A1 LIVIA MANZELLA YR 2020 UL http://ar.iiarjournals.org/content/40/5/2457.abstract AB 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.