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Identification of a novel fusion gene MLL‐MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23)
Author(s) -
Nemoto Noriko,
Suzukawa Kazumi,
Shimizu Seiichi,
Shinagawa Atsushi,
Takei Naoko,
Taki Tomohiko,
Hayashi Yasuhide,
Kojima Hiroshi,
Kawakami Yasushi,
Nagasawa Toshiro
Publication year - 2007
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20467
Subject(s) - fusion protein , fusion gene , biology , carcinogenesis , myeloid leukemia , cancer research , microbiology and biotechnology , gene , myelodysplastic syndromes , exon , leukemia , oncogene proteins , myeloid , genetics , regulation of gene expression , bone marrow , immunology , recombinant dna
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.