Post-InO–acquired determinants of resistance. (A) Number (top plot) and OncoPrint (bottom plot) of post-InO–acquired mutations. For each patient, acquired mutations were mutations present in post-InO but not in pre-InO. The dotted lines (at 300 and 900, number of post-InO–acquired mutations) were used as cutoff to divide patients into post-InO low-mutators, moderate-mutators, and hyper-mutators. (B) Fish plots showing acquisition of mutations in CD22 and KMT2D. (C) Mutational signatures of post-InO–acquired mutations in the hyper-mutators SJALL058834 (>10 bp insertions) and SJALL074541 (SBS6 and MMR-deficient). (D) A simplified schematic of the compromised G1/S DNA damage checkpoint by acquired mutations in InO-treated patients. SBS, single base substitution; DBS, doublet base substitution; HSCT, hematopoietic stem cell transplantation; NR, nonresponder. Figure created with BioRender.com.