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MLL-AF9-induced leukemogenesis requires coexpression of the wild-type Mll allele.

ABSTRACT: Oncogenic fusion proteins are capable of initiating tumorigenesis, but the role of their wild-type counterparts in this process is poorly understood. The mixed lineage leukemia (MLL) gene undergoes chromosomal translocations, resulting in the formation of oncogenic MLL fusion proteins (MLL-FPs). Here, we show that menin recruits both wild-type MLL and oncogenic MLL-AF9 fusion protein to the loci of HOX genes to activate their transcription. Wild-type MLL not only catalyzes histone methylation at key target genes but also controls distinct MLL-AF9-induced histone methylation. Notably, the wild-type Mll allele is required for MLL-AF9-induced leukemogenesis and maintenance of MLL-AF9-transformed cells. These findings suggest an essential cooperation between an oncogene and its wild-type counterpart in MLL-AF9-induced leukemogenesis.

SUBMITTER: Thiel AT

PROVIDER: S-EPMC2830208 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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MLL-AF9-induced leukemogenesis requires coexpression of the wild-type Mll allele.

Thiel Austin T AT Blessington Peter P Zou Tao T Feather Danielle D Wu Xinjiang X Yan Jizhou J Zhang Hui H Liu Zuguo Z Ernst Patricia P Koretzky Gary A GA Hua Xianxin X

Cancer cell 20100201 2

Oncogenic fusion proteins are capable of initiating tumorigenesis, but the role of their wild-type counterparts in this process is poorly understood. The mixed lineage leukemia (MLL) gene undergoes chromosomal translocations, resulting in the formation of oncogenic MLL fusion proteins (MLL-FPs). Here, we show that menin recruits both wild-type MLL and oncogenic MLL-AF9 fusion protein to the loci of HOX genes to activate their transcription. Wild-type MLL not only catalyzes histone methylation at ...[more]

PMID: 20159607

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