Figure 3.

Modeling the origin of AML. (A) Observations in transgenic mouse models suggest that AML driven by strong oncogenes such as MLL fusions mostly originates in multipotent progenitors: few cooperating mutations are needed to develop a symptomatic disease. In a minor fraction, the disease might occur from the HSC compartment leading to a particularly invasive and highly resistant phenotype. (B) A significant fraction of AML seems to be the product of cooperation of multiple mutations: early lesions in the HSC compartment provide a clonal advantage leading to a “preleukemic,” asymptomatic state; however, the gain of additional mutations (whether they occur in HSC or exclusively in more committed progenitor remains to be elucidated) is necessary to develop a symptomatic AML. AML = acute myeloid leukemia, BM = bone marrow, HSC = hematopoietic stem cell, MLL = mixed lineage leukemia.