Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 204, Issue 13, Pages 3059-3066Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20071637
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Funding
- NCI NIH HHS [R01 CA111560, CA115853, R21 CA115853, P01 CA068484, P01 CA109901, CA109901, CA11560, CA68484-11] Funding Source: Medline
- NIGMS NIH HHS [GM050237, R01 GM050237, R37 GM050237, R01 GM067055, GM067055] Funding Source: Medline
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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 similar to 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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