Defective lymphopoiesis and other developmental anomalies caused by Mysm1 deficiency were almost completely restored in p53−/−Mysm1−/− mice revealing a novel interaction of the histone-modifying enzyme 2A-DUB/Mysm1 and the ARF/p53 pathway, with potential relevance for lymphoma and leukemia development and other diseases. Here, MYSM1 is linked to leukemia.