Figure 1.

Associations and orders of acquired lesions in de novo, secondary, and therapy-related AMLs. (A) A schematic view of the multiple lesions underlying leukemogenesis and AML ontology, according to the classification in de-novo-type, secondary-type, and TP53-type AMLs—central lesions are shared by all types of AMLs, whereas outlying ones are either specific to or enriched in the type of AML indicated by the nearest arrow. Only the most frequent lesions are indicated in each category. (B) Fish diagrams of representative (but not exhaustive) clonal AML hierarchies in de novo AMLs. Grey areas show normal hematopoietic stem cells and their progeny. The onset of a clone is achieved through the acquisition of a genetic lesion (first lesion) and the subsequent expansion of mutant cells (colored cells and areas), as indicated in the top panel. Subsequent events will shape the clones with time and lead to AML. Lesions are color-coded, as indicated in panel A. (C) Fish diagrams showing representative (but not exhaustive) clonal AML hierarchies in secondary AMLs (s-AML) and therapy-related AMLs (t-AML), as in B.