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

2007; Rockefeller University Press; Volume: 204; Issue: 13 Linguagem: Inglês

10.1084/jem.20071637

1540-9538

Jennifer O’Neil, Joëlle Tchinda, Alejandro Gutiérrez, Lisa A. Moreau, Richard S. Maser, Kwok‐Kin Wong, Wei Li, Keith McKenna, X. Shirley Liu, Bin Feng, Donna Neuberg, Lewis B. Silverman, Daniel J. DeAngelo, Jeffery L. Kutok, Rodney Rothstein, Ronald A. DePinho, Lynda Chin, Charles Lee, A. Thomas Look,

Biochemical and Molecular Research

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 ∼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.