MLLT10 is a transcriptional regulator containing conserved zinc finger and leucine zipper domains that functions as a cofactor for DOT1L-mediated histone methylation. The protein binds unmodified histone H3 to regulate DOT1L catalysis of histone H3 lysine-79 dimethylation (H3K79me2) and gene activation, and also exhibits intrinsic transactivation activity when fused to other proteins. MLLT10 is primarily recognized for its role in acute leukemia through chr10 translocations. Patients with pediatric acute myeloid leukemia harboring MLLT10 fusions—particularly KMT2A::MLLT10, PICALM::MLLT10, and other rarer partners—demonstrate significantly adverse outcomes, with 5-year event-free survival of 18.6% compared to 49% in patients without MLLT10 fusions and elevated relapse risk of 76% 1. The KMT2A::MLLT10 fusion is an independent predictor of poor prognosis in pediatric AML 2. Recent clinical advances include approval of revumenib, a Menin-KMT2A interaction inhibitor, for treatment of relapsed or refractory KMT2A-rearranged acute leukemia 3. Beyond hematologic malignancy, MLLT10 variants are associated with endometriosis and related pain conditions through shared genetic pathways 4, and overexpression promotes colorectal cancer cell migration and invasion via epithelial-mesenchymal transition mechanisms 5.