On the other hand, the development of AML can be appreciated from a different light—rather than following a unidirectional, linear trajectory with LSCs representing the source of leukemogenesis, differentiated AML cells are also capable of reverting back to a relatively dedifferentiated, immature state via the suppression of the pioneer factor PU.1, for instance, suggesting transcriptional plasticity [125]. The gene discussed is SPI1; the disease is acute myeloid leukemia.