Different Classes of ABL1 Fusions Activate Different Downstream Signalling Nodes

Abstract

Abstract Background: Philadelphia-like acute lymphoblastic leukaemia (Ph-like ALL) is a high-risk subtype of ALL driven by a range of tyrosine kinase and cytokine receptor rearrangements. ABL1-class rearrangements (ABL1, ABL2, CSF1R and PDGFRB) account for 17% of Ph-like ALL cases in children, and are clinically important to identify as they can be therapeutically targeted with tyrosine kinase inhibitors (TKIs). While the p190 BCR-ABL1 fusion is well described, less is known about the function and downstream signalling by rare ABL1 fusions. We identified a rare ABL1 fusion, SFPQ-ABL1, in a paediatric B-ALL patient using RNA-sequencing. This fusion lacks the ABL1 Src-homology-3..