Figure 6.

A) Acute myeloid leukemia (AML) is a cancer of aberrant differentiation and proliferation of hematopoietic progenitor cells. Previous studies demonstrated that expression of inv(16) leukemogenic fusion protein CBFβ-SMMHC results differentiation block at multiple hematopoetic stages along with expansion of preleukemic stem/progenitor cells and abnormal myeloid progenitors, including CMP, Pre-Meg/E and MEP. These preleukemic stem/progenitor cells and abnormal myeloid progenitors are susceptible to malignant transformation into leukemia-initiating cells that drive and sustain AML pathogenesis. B) Schematic illustration of AML pathogenesis in the differentiation continuum. To simulate inv(16) driven AML, the proliferation R_k(x) connecting the nodes 3, 5, and 11 is increased and the flow toward the node 11, V_k(x) and D_k(x) for k = I(i, 11) is blocked.