Figure 3. Variation among leukemias in the degree and nature of hierarchical organization.

Although most AMLs follow a cancer stem cell model, the surface marker phenotypes of the leukemogenic cells vary from patient to patient. (A–C) Different oncogenic mutations can transform cells at different levels within the hematopoiesis hierarchy (Wang et al., 2010), potentially influencing the frequency, spectrum, and phenotype of cells with leukemogenic potential. Interconversion between leukemogenic cell populations would allow any population to recapitulate the heterogeneity of the leukemogenic cell pool (Eppert et al., 2011; Sarry et al., 2011). (D) Some mutations, such as MLL-AF9 translocations, can confer leukemogenic activity upon restricted progenitors (Cozzio et al., 2003; Huntly et al., 2004; Krivtsov et al., 2006; Zhao et al., 2010). (E) If multiple populations have leukemogenic capacity but do not interconvert, then only the most immature cells can recapitulate the full heterogeneity of the parent leukemia but multiple levels of the hierarchy may be able to drive disease progression (Goardon et al., 2011). (F) In some ALLs many cells have leukemogenic activity despite heterogeneity in marker expression (le Viseur et al., 2008; Williams et al., 2007).