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Molecular Cytogenetics

Cloning and sequence analysis of four t(9;11) therapy-related leukemia breakpoints

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Abstract

The t(9;11)(p22;q23) is the most common chromosomal translocation in topoisomerase II inhibitor therapy-related acute myeloid leukemia (tAML). This translocation fuses the MLL and AF9 proto-oncogenes producing a novel chimeric protein. In order to gain insight into the mechanism generating the t(9;11) and to clarify the role topoisomerase II inhibition may play in that mechanism we have cloned and sequenced the breakpoints from four tAML patients with the t(9;11). This sequence analysis identifies topoisomerase II consensus binding sequences near or at the chromosome 11 and chromosome 9 breakpoints in all four patients. One patient also had the consensus binding sequence for the TRANSLIN DNA-binding protein at the 9p22 and 11q23 breakpoints. Our results further support a direct role for topoisomerase II in the genesis of these tAML translocations.

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Author notes

  1. M Atlas

    Present address: Department of Pediatrics, Division of Oncology, Columbia University, New York, NY, USA

  2. D Burian

    Present address: Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK, USA

Authors and Affiliations

  1. Department of Pediatrics, Section of Hematology-Oncology, Northwestern Univerity, Chicago, IL, USA

    M Atlas & E Schmidt

  2. Department of Pathology, St Judes Childrens Research Hospital, Memphis, TN, USA

    D Head & F Behm

  3. Department of Medicine, Section of Hematology Oncology, University of Chicago, Chicago, IL, USA

    NJ Zeleznik-Le

  4. Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, USA

    BA Roe & D Burian

  5. Department of Pathology, University of Chicago, Chicago, IL, USA

    PH Domer

Authors
  1. M Atlas
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  2. D Head
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  3. F Behm
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  4. E Schmidt
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  5. NJ Zeleznik-Le
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  6. BA Roe
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  7. D Burian
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  8. PH Domer
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Atlas, M., Head, D., Behm, F. et al. Cloning and sequence analysis of four t(9;11) therapy-related leukemia breakpoints. Leukemia 12, 1895–1902 (1998). https://doi.org/10.1038/sj.leu.2401223

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  • DOI: https://doi.org/10.1038/sj.leu.2401223

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