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Regulation of the cyclin A1 protein is associated with its differential subcellular localization in hematopoietic and leukemic cells

Oncogene volume 23, pages 9082–9089 (2004)Cite this article

Abstract

An important role of the cell cycle regulatory protein cyclin A1 in the development of acute myeloid leukemia (AML) was previously demonstrated in a transgenic mouse model. We have now turned our attention to study specific aspects of the activity and subcellular distribution of cyclin A1 using bone marrow samples from normal donors and patients with AML, as well as leukemic cell lines. We show that the localization of cyclin A1 in normal hematopoietic cells is nuclear, whereas in leukemic cells from AML patients and cell lines, it is predominantly cytoplasmic. In leukemic cell lines treated with all-trans retinoic acid (ATRA), cyclin A1 localized to the nucleus. Further, there was a direct interaction between cyclin A1 and cyclin-dependent kinase 1, as well as a major ATRA receptor, RARα, in ATRA-treated cells but not in untreated leukemic cells. Our results indicate that the altered intracellular distribution of cyclin A1 in leukemic cells correlates with the status of the leukemic phenotype.

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Acknowledgements

We thank Elise Nilsson and Karl Bacos for the technical assistant, and Stefan Karlsson (Division of Molecular Medicine and Gene therapy, Lund) for helpful discussions. This work was supported by grants from Swedish Cancer Society, Swedish Children's Cancer Foundation, MAS Cancer Fondation, Kungliga Fysiografiska Sälskapet in Lund, Crafoordska stiftelsen, and MAS foundation (JLP); the Government Public Health Grant and Swegene/WCN (GL), and the NIH (CA09363 and CA95362) (DJW).

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Authors and Affiliations

  1. Division of Pathology, Department of Laboratory Medicine, Lund University, University Hospital, Malmö, S-205 02, Sweden

    Jenny Ekberg, Göran Landberg, Caroline Holm & Jenny Liao Persson

  2. Division of Molecular Medicine and Gene Therapy, BMC, Lund, S-221 84, Sweden

    Johan Richter

  3. Department of Genetics and Development, The Center for Reproductive Sciences and The Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, 10032, New York, USA

    Debra J Wolgemuth

  4. Department of Obstetrics and Gynecology, The Center for Reproductive Sciences and The Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, 10032, New York, USA

    Debra J Wolgemuth

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  1. Jenny Ekberg
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Correspondence to Jenny Liao Persson.

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Ekberg, J., Landberg, G., Holm, C. et al. Regulation of the cyclin A1 protein is associated with its differential subcellular localization in hematopoietic and leukemic cells. Oncogene 23, 9082–9089 (2004). https://doi.org/10.1038/sj.onc.1208090

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