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Effects of SET and SET-CAN on the differentiation of the human promonocytic cell line U937

Leukemia volume 18, pages 337–340 (2004)Cite this article

Abstract

Human SET encodes a nuclear phosphoprotein with a highly acidic carboxyl-terminus, forming a SET-CAN fusion gene in a patient with acute undifferentiated leukemia. SET is highly conserved between species and is ubiquitously expressed, suggesting a widespread biological role. Even though SET is involved in chromatin remodeling and transcriptional activation, its precise role in hematopoietic cells and the contribution of SET-CAN to leukemogenesis remains unknown. We determined the effect of tetracycline-regulatable expression of SET, a deletion mutant of SET, and SET-CAN on the human promonocytic cell line U937T. The expression of SET and SET-CAN inhibited proliferation of these cells. SET accomplishes this through the induction of the differentiation program, an effect that depends on the presence of its acidic domain. SET-CAN most likely inhibits growth by interfering with hCRM1, but it also partially blocks differentiation. Our results are the first demonstration of a potential role of SET in hematopoietic differentiation.

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Acknowledgements

We thank Dr Richard Ashmun and Dr Ann Marie Hamilton-Easton for FACS analysis, Dr Andrew Hollenbach for help with the paper, Dr Irina Lagutina for suggestions regarding immunocytochemistry and Dr Terry Copeland for SET antibody. This work was supported by NIH Grant CA76480-05, the Cancer Center (CORE) Support Grant CA-21765, and the American Lebanese Syrian Associated Charities (ALSAC) of St Jude Children's Research Hospital.

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Authors and Affiliations

  1. Department of Genetics, St Jude Children's Research Hospital, Memphis, TN, USA

    A Kandilci & G Grosveld

  2. Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands

    E Mientjes

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  1. A Kandilci
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  2. E Mientjes
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  3. G Grosveld
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Correspondence to G Grosveld.

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Kandilci, A., Mientjes, E. & Grosveld, G. Effects of SET and SET-CAN on the differentiation of the human promonocytic cell line U937. Leukemia 18, 337–340 (2004). https://doi.org/10.1038/sj.leu.2403227

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