| RRC ID |
43000
|
| 著者 |
Nemoto N, Suzukawa K, Shimizu S, Shinagawa A, Takei N, Taki T, Hayashi Y, Kojima H, Kawakami Y, Nagasawa T.
|
| タイトル |
Identification of a novel fusion gene MLL-MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23).
|
| ジャーナル |
Genes Chromosomes Cancer
|
| 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.
|
| 巻・号 |
46(9)
|
| ページ |
813-9
|
| 公開日 |
2007-9-1
|
| DOI |
10.1002/gcc.20467
|
| PMID |
17551948
|
| MeSH |
Aged
Antineoplastic Agents / adverse effects
Chromosomes, Human, Pair 11 / genetics*
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
Exons
Female
Histone-Lysine N-Methyltransferase
Humans
Leukemia, Myeloid, Acute / chemically induced
Leukemia, Myeloid, Acute / genetics*
Leukemia, Myeloid, Acute / metabolism
Male
Middle Aged
Myelodysplastic Syndromes / genetics*
Myelodysplastic Syndromes / metabolism
Myeloid-Lymphoid Leukemia Protein / genetics*
Myeloid-Lymphoid Leukemia Protein / metabolism
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
Oncogene Proteins, Fusion / genetics*
Oncogene Proteins, Fusion / metabolism
Protein Structure, Tertiary
Trans-Activators
Transcription Factors / genetics*
Transcription Factors / metabolism
|
| IF |
3.444
|
| 引用数 |
29
|
|
WOS 分野
|
GENETICS & HEREDITY
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
KG-1(RCB1166)
293(RCB1637) |
