In CML, EZH2 inactivation leads to contraction of the LSC compartment and impaired disease maintenance in vivo, independent of BCR-ABL1 status.100 In AML, EZH2 facilitates tumorigenesis by repressing phosphatase and tensin homolog (PTEN), which encodes a major tumor suppressor.101 Notably, dual deletion of EZH1 and EZH2 from AML cells results in complete remission through increased differentiation, suggesting a critical function of these epigenetic modifiers in leukemogenesis.104 However, whether such a function is mechanistically linked to the LSC compartment remains to be determined. Here, ABL1 is linked to acute myeloid leukemia.