MXD4 has been implicated in the mutated Flt signaling of Flt3-ITD-induced myeloproliferative disease, which indicates that MXD4 may play a critical role in myeloid malignancies.48 Our findings that blocking MXD4 weakens the effect of UHRF1 defects on self-renewal of LICs indicate that MXD4/MYC/E2F axis functioned as an important regulator of leukemogenesis. Here, UHRF1 is linked to myeloproliferative disorder.