A model of clonal evolution of FLT3-ITD⁺AML during sorafenib treatment and NOD/SCID engraftment. Multiple clones were present in blasts_naive. Sorafenib induced differentiation in AML, leading to CRi. However, sorafenib resistant clones, in some cases carrying double FLT3-ITD and D835 mutations, emerged and leukemia relapse ensued, giving rise to blast_sresist. These double-mutant clones could be further enriched in NOD/SCID mice because of their superior engrafting potential.