Fig. 1: The clonal relationship between AML and ALL.

a, Schematic overview of different relations between an ALL and subsequent AML from the same patient and corresponding mutational readouts. (i) The AML and ALL may be clonally unrelated malignancies, sharing no mutations, as is the case for treatment-related AML (t-AML). (ii) They may arise from a common precursor cell, typified by shared somatic mutations likely including a first driver mutation, but is itself not a cancer cell. (iii) The AML may derive from the ALL, which has undergone a true lineage switch through transdifferentiation, typified by the AML harboring all somatic mutations of the primary ALL. Note that asynchronous presentations of ALL and AML may involve mutations in the second lesion induced by the therapy for the first lesion. b, A fish plot showing the clone size of the different ALL and AML clones over the course of the clinical history of the patient. Number in parentheses after sample identifier refers to the genome-wide coverage of sequencing. mths, months; MDS, myelodysplastic syndrome. c, Reconstructed phylogeny of clones with annotated putative driver mutations and CNVs. Number of single base substitution mutations underlying each branch of the phylogenetic tree are denoted above the branch. Dashed lines group clones into initial ALL, ALL relapses and AML relapses. fs, frameshift; del, deletion; rearr., rearrangement.