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Fusion of retinoic acid receptor α to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia

Nature Genetics volume 17, pages 109–113 (1997)Cite this article

Abstract

Acute promyelocytic leukaemia (APL) is uniquely associated with chromosomal translocations that disrupt the gene encoding the retinoic acid receptor, RARA. In more than 99% of cases, this disruption results in the formation of a PML-RARA gene fusion1–4. Two rare variants of APL have been described, in which RARA is fused to one of two other genes, PLZF5 and NPM6 . Although RARA dysregulation is evidently important in APL, the role of the various fusion partners remains unclear. We have characterized a fourth APL gene fusion, which links exons encoding the retinoic acid and DMA-binding domains of RARA to 5′ exons of NuMA, a gene that encodes the nuclear mitotic apparatus protein7,8. The NuMA-RARA fusion protein exists in sheet-like nuclear aggregates with which normal NuMA partly co-localizes. In contrast to t(15;17) APL, the intracellular distribution of PML is normal in these cells. Our results suggest that interference with retinoid signalling, and not disruption of PML organization, is essential to the APL phenotype and implicates for the first time an element of the mitotic apparatus in the molecular pathogenesis of human malignancy.

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Author notes

  1. Richard A. Wells

    Present address: Division of Hematology-Oncology, Children's Hospital and Dana Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, 02115, USA

Authors and Affiliations

  1. Department of Hematology, The Toronto Hospital, University of Toronto, 100 College Street, Room 128, Toronto, Ontario, M5G115, Canada

    Richard A. Wells & Suzanne Kamel-Reid

  2. The Ontario Cancer Institute, Princess Margaret Hospital, the Department of Pathology, The Toronto Hospital,

    Richard A. Wells & Suzanne Kamel-Reid

  3. the Departments of Cellular and Molecular Pathology and Medicine, University of Toronto, 100 College Street, Room 128, Toronto, Ontario, M5G 1L5, Canada

    Richard A. Wells & Suzanne Kamel-Reid

  4. Department of Laboratory Medicine, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada

    Charles Catzavelos

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  3. Suzanne Kamel-Reid
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Wells, R., Catzavelos, C. & Kamel-Reid, S. Fusion of retinoic acid receptor α to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia. Nat Genet 17, 109–113 (1997). https://doi.org/10.1038/ng0997-109

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