Characterization of AML cases with adaptive resistance. (A) Genomic landscape of AML cases with adaptive resistance. Molecular mutations in 25 patients with relapsed AML after an initial response. The presence of adverse cytogenetic risk, complex karyotype, del(17p), indicated mutations, study ID number, relapse-free survival, and cytotoxic therapy received (AZA, azacitidine; DEC, decitabine or LDAC, low-dose cytarabine) are shown for each case. The bar graphs (right side of the plot) summarize the number of cases with persistent, expanded, acquired, or reduced/cleared mutations at relapse. (B-F) Dynamic changes in clonal architecture from diagnosis to relapse in 5 cases with FLT3-ITD. The VAF for each mutation is shown, along with the bone marrow blast count at the corresponding time point. The time elapsed from remission to treatment failure is shown in days. (G-H) Single-cell analysis of clonal architecture at screening and relapse. Mission Bio Tapestri clonograms showing the relative mutation composition (%) of samples at indicated time points for cases #041 (G) and #392 (H). In case #041 (G), the NPM1 and IDH1 parental clone included 2 PTPN11mut subclones, which were extinguished, and a FLT3-ITD subclone, which expanded at relapse. In case #392 (H), the proportion of WT and SRSF2mut-only cells have decreased and been replaced by 4 new clones activating the FLT3 or NRAS kinase pathways.