Proposed models of AML transformation. Three proposed simplified scenarios of step-wise transformation in human AML, leading from a normal cell (green) to a premalignant cell (light red) and, eventually, to a malignant cell (dark red) with clonal expansion: Scenario 1, both the initial transforming event and subsequent mutations leading to clonal expansion occur at the level of multipotent, CD33⁻ precursors; Scenario 2, the initial transforming event occurs at the level of multipotent, CD33⁻ precursors, whereas the collaborating mutational event leading to clonal expansion occurs at the level of CD33⁺ committed myeloid progenitors; and Scenario 3, both initial and subsequent mutations occur at the level of CD33⁺ committed myeloid precursors. Similar models have been proposed by others.¹²⁹