Stem Cell Modeling of Core Binding Factor Acute Myeloid Leukemia

Figure 1

Simplified schematics of clonal evolution in leukemia. According to “clonal evolutionary theory,” soon after the initial leukemogenic event (here represented by a “lightning bolt”), that is, a first “class-2” mutation leading to expansion of a preleukemic clone (A), additional genetic mutations (again represented by “lightning bolts”) accumulate inside the cell population (B), creating a heterogeneous environment in which several distinct subclones compete for dominance (C). These subclones may later expand or spontaneously disappear (as here subclones 2a, 4, 4a, 5, and 5a do; clonal disappearance is marked by “X”) as a consequence of the selective pressure by intrinsic and extrinsic determinants (D). After the acquisition of “class-1” mutations, overt leukemia arises to clinical diagnosis (E) consisting of a dominant clone (3a in the Figure) and various subclones (1, 2, and 3).