Dynamics of clonal evolution during the development of hematological malignancies. Little is known about the dynamics of clonal evolution following successive mutation acquisition. Six different models are presented (A-F). The horizontal axis is time and the vertical space represents clonal expansion. Green, orange, and red lines represent sequential driver mutation acquisition, with red representing the final malignant clone. The Armitage and Doll multistep model of cancer development,⁹⁴  in which there is no premalignant clonal expansion, is shown in panel A. Rare, single-driver–mediated malignant transformation is shown in panel B. In models (panels C-F), each mutation results in sequential clonal expansion along a path to malignancy. However, the dynamics of clonal expansion show different patterns. MLL, mixed lineage leukemia.