In summary, ReSisTrace lineage-tracing offers a powerful tool forelucidating intricate cellular states that prime treatment resistance also inhematological cancers, as demonstrated here in the context of FLT3-ITD-mutated AML.Furthermore, our study unveils novel synergistic and pre-sensitizing drugs thatcould potentially be used to increase FLT3 inhibitor treatment efficacy and preventemergence of treatment resistance against FLT3 inhibitors in FLT3-ITD-positiveAML. Here, FLT3 is linked to acute myeloid leukemia.