Clonal evolution from primary to REL in UPN001 and UPN002 and pattern of evolution observed in 13 DX and REL pairs. (A,D) Distribution of variant allele frequencies (VAFs) of validated mutations at DX and REL (UPN001 and UPN002). VAFs of genes in region of uniparental disomy are halved. Driver mutations, including FLT3-ITD, are indicated. Two mutational clusters were identified at DX and 2 were present at REL; 1 was present at both DX and REL. (B,E) Graphic representation of the relationship between clusters at DX and REL. Gray cluster represents founding clone at DX and REL. (C,F) Schematic representation of mutational clones and their evolution from DX to REL. Founder clone at DX evolved into REL clones by acquiring REL-specific mutations. HSC, hematopoietic stem cell.