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Potential Topoisomerase II DNA-binding Sites at the Breakpoints of a t(9;11) Chromosome Translocation in Acute Myeloid Leukemia¹

Jefferson Cancer Institute and Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 [M. N., T. N., E. C., C. M. C.], and Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104 [C. A. F., C. M., B. J. L.]

² To whom requests for reprints should be addressed, at Jefferson Cancer Institute, Thomas Jefferson University, Bluemle Life Science Bldg, Room 1050, 233 S. 10th Street, Philadelphia, PA 19107.

We have examined a t(9;11)(p22;q23) chromosome translocation in an acute myeloid leukemia of an infant. The breakpoints on the two chromosomes occurred within introns of the involved genes: AF-9 on chromosome 9, and ALL-1 on chromosome 11. Sequence analysis identified hep-tamers flanking the breakpoints on both chromosomes 9 and 11, suggesting that the V-D-J recombinase was involved in the translocation. The presence of an N-region between the two chromosomes supports the hypothesis that a mistake in V-D-J joining was involved in the genesis of the translocation and indicates that terminal deoxynucleotidyl transferase was expressed in the cells from which this acute myeloid leukemia originated. In addition, potential topoisomerase II DNA-binding sites were found near the breakpoints of both chromosomes, suggesting the involvement of altered topoisomerase II activity in this translocation. Altered topoisomerase II activity in the presence of an active V-D-J recombinase may be a pathogenetic mechanism of acute myeloid leukemia with rearrangements at 11q23.

¹ This study was supported by an Outstanding Investigator Award (CA39860) to C. M. C. from the National Cancer Institute and an Award from the Falck Medical Research Trust. C. M. is a recipient of a fellowship from the Ministerio de Educacion y Ciencia of Spain.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 8/16/93. Accepted 8/27/93.

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