Figure 5: Founding lesions define distinct genetic hierarchies and clonal histories in AML.
From: Genetic hierarchy and temporal variegation in the clonal history of acute myeloid leukaemia
(a) In 49 patients with lesions in epigenetic regulators first, subsequent events were classified as early intermediate (second to median), late intermediate (median+1 to penultimate) and last event. Histograms show the distribution of events at each chronological position. * indicate P<0.05, Fisher’s exact test. (b) Co-mutation table of 72 AMLs at diagnosis. The bottom left colour code indicates the position of each lesion as defined in a; hatched boxes mean ⩾2 lesions at distinct positions. Groups of patients with distinct genetic hierarchies were defined according to the co-occurrence or exclusion of mutations in the three master genes involved in CHIP—DNMT3A, TET2, ASXL1—, mutations in NPM1 and in haematopoietic transcription factors—RUNX1, GATA2, CEBPA— and pre-leukaemic chromosomal aberrations—MLL and CBF rearrangements, del(20q). Clonal composition of representative AMLs with distinct genetic hierarchies are shown in boxes surrounding the mutation table. s-AML, secondary AML; t-AML, therapy-related AML. Internally tangent circles represent successive events. Colours are as in Fig. 2a.
