Stem Cell Modeling of Core Binding Factor Acute Myeloid Leukemia

Figure 2

Proposed model for leukemogenesis. According to this model, AML arises following (at least) three different scenarios. In the first one (1) both “class-2” (represented as “light grey lightning bolts”) and “class-1” (“dark grey lightning bolts”) mutagenic events happen in the HSC (“white dotted circles”), thus creating a rapidly expanding clone endowed by some of the persisting physiological abilities of HSC, such as self-renewal ability (all cells with self-renewal abilities are represented as “dotted circles” in the figure). The resulting leukemia therefore contains more L-IC (represented by “grey dotted circles”), with consequences on the resistance to chemotherapy and the chance of relapse. In the second scenario (2) an initial “class-2” event gives rise to a preleukemic phase where different subclones (“light grey circles”) compete one another and with residual hematopoiesis (“white circles”) until the emergence of a dominant clone which benefits from self-renewal ability (“dark grey dotted circles”), conferred by an additional “class-1” mutation. This is the scenario thought to model leukemogenesis in the case of CBF AML. In the last scenario (3) leukemia arises from “class-2” and “class-1” events both happening in early committed HPP; leukemia therefore consists mainly of dysplastic HPP which are possibly more sensitive to chemotherapy and agents forcing differentiation.