title: Identification of a novel fusion gene MLL-MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23).
abstract: We have identified a novel fusion partner of MLL, namely the mastermind like 2 (MAML2 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 MAML2 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.
authors.affiliation: Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Ibaraki 305-8575, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Nemoto
authors.forename: Kazumi
authors.initials: K
authors.lastname: Suzukawa
authors.forename: Seiichi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shinagawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Takei
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taki
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kojima
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Toshiro
authors.initials: T
authors.lastname: Nagasawa
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; C471297:MAML2 protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase