Leukaemia-driving oncogenes (e.g., RUNX1-RUNXT1, PML-RARA, TCF3-HLF, IDH1/2, TET2) or treatment with targeted agents directed against aberrant kinases (e.g., JAK1/2 and FLT3 inhibitors) have been associated with reduced DNA repair gene expression/activity that would render leukaemia blasts selectively sensitive to synthetic lethality induced by poly(ADP-ribose) polymerase inhibitors (PARPi).
Finally, we also showed in an in vivo leukemia model that cells expressing JAK1(A634D) are hypersensitive to the antiproliferative and antitumorigenic effect of type I IFN, suggesting that type I IFNs should be considered as a potential therapy for ALL with JAK1-activating mutations.