Asciminib is a novel inhibitor of ABL1 and ABL2 gene fusions in ALL but requires the ABL SH3 domain for efficacy

This is the authors' abstract. We don't add key points for this paper.

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).