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

Genes Chromosomes Cancer. 2007 Sep;46(9):813-9. doi: 10.1002/gcc.20467.

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.

Publication types

  • Case Reports

MeSH terms

  • 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

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • KMT2A protein, human
  • MAML2 protein, human
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Trans-Activators
  • Transcription Factors
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase