Asciminib is a novel inhibitor of <i>ABL1</i> and <i>ABL2</i> gene fusions in ALL but requires the ABL SH3 domain for efficacy
Laura N Eadie, Elias Lagonik, Elyse C. Page, Caitlin E Schutz, Susan L. Heatley, Barbara J. McClure, Michelle O. Forgione, David T Yeung, Timothy P. Hughes, Deborah L. White
Abstract
We read with interest the recent publication by van Outersterp et al 1 describing the differential sensitivity of acute lymphoblastic leukemia (ALL) ABL-class gene fusions to adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitors (TKIs).The aforementioned study investigated the efficacy of imatinib, dasatinib, and bosutinib in cell lines harboring ABL1 (n = 7), ABL2 (n = 1), PDGFRB (n = 11), and CSF1R (n = 2) gene fusions and reported that lack of Src homology 3 (SH3) domain does not confer resistance to TKIs.Here, we report additional data for the efficacy of the TKIs nilotinib and ponatinib, as well as the myristate pocket-targeted allosteric inhibitor asciminib, against ABL1 (n = 5) and ABL2 (n = 3) gene fusions, collectively referred to as ABL rearrangements (ABLrs).