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Acute Non Lymphocytic Leukemia

A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquitin-specific protease gene USP42

Leukemia volume 20, pages 224–229 (2006)Cite this article

Abstract

Although many of the chromosomal abnormalities in hematologic malignancies are identifiable cytogenetically, some are only detectable using molecular methods. We describe a novel cryptic t(7;21)(p22;q22) in acute myeloid leukemia (AML). FISH, 3′RACE, and RT-PCR revealed a fusion involving RUNX1 and the ubiquitin-specific protease (USP) gene USP42. The genomic breakpoint was in intron 7 of RUNX1 and intron 1 of USP42. The reciprocal chimera was not detected – neither on the transcriptional nor on the genomic level – and FISH showed that the 5′ part of USP42 was deleted. USP42 maps to a 7p22 region characterized by segmental duplications. Notably, 17 kb duplicons are present 1 Mb proximal to USP42 and 3 Mb proximal to RUNX1; these may be important in the genesis of t(7;21). This is the second cryptic RUNX1 translocation in hematologic malignancies and the first in AML. The USPs have not previously been reported to be rearranged in leukemias. The cellular context in which USP42 is active is unknown, but we here show that it is expressed in normal bone marrow, in primary AMLs, and in cancer cell lines. Its involvement in the t(7;21) suggests that deregulation of ubiquitin-associated pathways may be pathogenetically important in AML.

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Acknowledgements

This study was supported by grants from the Swedish Cancer Society, the Swedish Children's Cancer Foundation, and Gunnar Nilsson's Cancer Foundation.

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Authors and Affiliations

  1. Department of Clinical Genetics, Lund University Hospital, Lund, Sweden

    K Paulsson, F Mitelman, B Johansson & I Panagopoulos

  2. Department of Pediatrics, Lund University Hospital, Lund, Sweden

    A N Békássy

  3. Department of Hematology, Lund University Hospital, Lund, Sweden

    T Olofsson

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  1. K Paulsson
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  2. A N Békássy
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  4. F Mitelman
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Correspondence to K Paulsson.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Paulsson, K., Békássy, A., Olofsson, T. et al. A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquitin-specific protease gene USP42. Leukemia 20, 224–229 (2006). https://doi.org/10.1038/sj.leu.2404076

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