Germ line MBD4-deficient patients share a common path to AML. Clonal evolution and phylogenetic tree diagram highlighting the acquisition of key driver mutations and clonal dynamics in WEHI-AML-1 (A) and in EMC-AML-1 (B). (C) The phylogenetic tree diagram for key driver mutations in WEHI-AML-2. Variant allele frequencies were derived from whole exome sequencing data or deep sequencing for all cases. For EMC-AML-1 single-cell genotyping was used to resolve the clonal relationships. Clones are represented by different colors, and the vertical lines in the top panels indicate sampling points. The premalignant clone (P, in dark blue) and the AML clones evident at diagnosis (D, in red) and relapse (R, in yellow) are designated. Both WEHI-AML-1 and EMC-AML-1 experienced clonal hematopoiesis during remission. The transplant for WEHI-AML-1 was provided by WEHI-AML-2, which occurred 4 years prior to her own diagnosis of AML.