Alu elements mediate MYB gene tandem duplication in human T-ALL.

Document Type

Article

Publication Date

2007

Keywords

Base-Sequence, Gene-Duplication, Humans, In-Situ-Hybridization-Fluorescence, Leukemia-Lymphoma-Adult-T-Cell, Models-Biological, Models-Genetic, Molecular-Sequence-Data, Nucleic-Acid-Hybridization, Polymerase-Chain-Reaction, Proto-Oncogene-Proteins-c-myb, Recombination-Genetic

First Page

3059

Last Page

3066

JAX Source

J Exp Med 2007 Dec; 204(13):3059-66.

Abstract

Recent studies have demonstrated that the MYB oncogene is frequently duplicated in human T cell acute lymphoblastic leukemia (T-ALL). We find that the human MYB locus is flanked by 257-bp Alu repeats and that the duplication is mediated somatically by homologous recombination between the flanking Alu elements on sister chromatids. Nested long-range PCR analysis indicated a low frequency of homologous recombination leading to MYB tandem duplication in the peripheral blood mononuclear cells of approximately 50% of healthy individuals, none of whom had a MYB duplication in the germline. We conclude that Alu-mediated MYB tandem duplication occurs at low frequency during normal thymocyte development and is clonally selected during the molecular pathogenesis of human T-ALL.

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