Stem Cell Hierarchy and Clonal Evolution in Acute Lymphoblastic Leukemia

Figure 1

Different models explaining tumor cell heterogeneity. The cancer stem cell model describes stem cell-like LICs at the apex of a tumor cell differentiation hierarchy, exclusively having self-renewal potential and giving rise to all other cells of the leukemic bulk cells, which do not have LIC activity. In contrast, the clonal evolution models show no differentiation hierarchy and the main assumption is that individual subclones acquire successive mutations resulting in an ongoing subclonal evolution leading to intratumoral heterogeneity either in a linear or branching fashion. Importantly, these models are not mutually exclusive and a combination of both models contributes to tumor cell heterogeneity.