Analysis of serial samples. Scatter plots showing variant allele fractions (VAF) at time of paired samples at (A) MDS and s-AML and (B) diagnosis and morphologic CR. Colors show ontogeny specificity of mutated genes including secondary-type (blue); TP53 (green); and de novo/pan-AML subsets, including RAS pathway and myeloid transcription factors (red), TET2 and DNMT3A (yellow), and other pan-AML (gray). Mutations were categorized as new if they were detected in s-AML but present below 1% allele frequency in MDS (85%), or if their allele frequency increased from ≤10% in MDS to >30% in the subsequent s-AML (15%). Mutations were labeled as selectively lost only if variant allele fraction was <0.5% at remission. (C) Pie chart showing s-AML progression mutations by functional class. (D) Representative fish plots from 2 cases with subclonal remissions showing clonal architecture at diagnosis (indicated by a red line—AML) and after treatment at time of morphologic CR (indicated by a red line—CR). In both cases, clonal remission is characterized by disappearance of progression mutations and relative persistence of founder mutations despite the absence of bone marrow myeloblasts.