Subsequent genetic SCA of engrafted single HSPCs and HSPC-derived subclones using next-generation sequencing (NGS) with a panel of common AML mutations demonstrated that relapse-associated subpopulations were endowed with a specific genetic makeup, i.e., mutated EZH2 and TP53, which were present already at diagnosis. The gene discussed is EZH2; the disease is acute myeloid leukemia.