Our data suggest that the epigenetic silencing of UBXN8 mediated by the RUNX1-RUNX1T1 oncoprotein contributes to the leukemogenesis of t(8;21) AML and that UBXN8 plays a tumor suppressor role in t(8;21) AML; thus, enhancing UBXN8 expression may be a potential treatment option for t(8;21) AML. The gene discussed is UBXN8; the disease is acute myeloid leukemia.