Impaired DNA Replication within Progenitor Cell Pools Promotes Leukemogenesis
Figure 9
In a wild-type, healthy progenitor cell pool, potentially oncogenic mutations (represented as a red “X” in a cell) will often provide little or no advantage in the short term, and may even be disadvantageous (top images). In contrast, in a replication-impaired hematopoietic system (bottom images), acquisition of some oncogenic mutations should provide a selective advantage by partly or fully restoring cell cycle progression, even when the same mutation might be disadvantageous in a wild-type pool. The preferential expansion of the mutated population increases the target size and thus the chances for additional mutations and cancer. In this figure, the rectangle indicates the limited niche size, implying competition for contacts and growth factors. The thickness of curved arrows indicates proliferative ability.