Identification of a novel fusion gene MLL‐MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23)

We have identified a novel fusion partner of MLL , namely the mastermind like 2 ( MAML 2 gene), in secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with inv(11)(q21q23). RT‐PCR and sequencing revealed that exon 7 of MLL was fused to exon 2 of MAML 2 in the AML and MDS cells. The inv(11)(q21q23) results in the creation of a chimeric RNA encoding a putative fusion protein containing 1,408 amino acids from the NH2‐terminal part of MLL and 952 amino acids from the COOH‐terminal part of MAML2. The NH2‐terminal part of MAML2, a basic domain including a binding site of the intracellular domain of NOTCH, was deleted in MLL‐MAML2. MLL‐MAML2 in secondary AML/MDS and MECT1‐MAML2 in mucoepithelioid carcinoma, benign Wartin's tumor, and clear cell hidradenoma consist of the same COOH‐terminal part of MAML2. A luciferase assay revealed that MLL‐MAML2 suppressed HES1 promoter activation by the NOTCH1 intracellular domain. MAML2 involving a chimeric gene might contribute to carcinogenesis in multiple neoplasms by the disruption of NOTCH signaling. © 2007 Wiley‐Liss, Inc.