USP10, a primary cytoplasmic DUB, acts as an oncogene or a tumor suppressor by regulating various protein substrates, including FLT3, p53, AMPK, PTEN, etc. USP10 was identified as a critical DUB for the stabilization of FLT3, whose oncogenic forms are clinically validated targets in acute myeloid leukemia (AML). Here, TP53 is linked to acute myeloid leukemia.