It is typically necessary to prove the diagnosis of secondary tumors, rather than a lineage switch at relapse, for types of leukemia that demonstrate increased lineage plasticity [56,57,58], such as AL with KMT2A, ZNF384 or DUX4 gene rearrangements or early T-cell acute lymphoblastic leukemia (ETP-ALL) [59,60]. The gene discussed is DUX4; the disease is leukemia.