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Downregulation of MLL-CBP fusion gene expression is associated with differentiation of SN-1 cells with t(11;16)(q23;p13)

Oncogene volume 20, pages 375–384 (2001)Cite this article

Abstract

The translocation t(11;16)(q23;p13) has only been documented in patients with acute leukemia or myelodysplasia secondary to therapy with drugs targeting DNA topoisomerase II. We have established a myeloid cell line (SN-1) with the MLL-CBP fusion gene from an acute leukemia patient with t(11;16)(q23;p13). Although SN-1 cells were not induced to differentiate by all-trans retinoic acid (ATRA) and 1α,25-dihydroxyvitamin D3 (VD3), retinoid X receptor (RXR) agonists, such as 9-cis retinoic acid and Ro48-2250, effectively induced differentiation of the cells. Downregulation of the expression of the MLL-CBP fusion gene occurred during the differentiation of SN-1 cells. When SN-1 cells were treated with MLL-CBP antisense oligonucleotide, the cells were induced to differentiate by ATRA or VD3, suggesting that the MLL-CBP fusion gene dominant-negatively suppresses ATRA- or VD3-induced differentiation. Moreover, suboptimal concentrations of sodium butyrate, a histone deacetylase inhibitor, had a cooperative effect with ATRA or VD3 in inducing the differentiation of SN-1 cells. The downregulation of the expression of MLL-CBP mRNA was accompanied by the induction of differentiation. These findings suggest that RXR agonists or a clinically applicable combination of ATRA and butyrate derivatives might be useful for differentiation therapy in leukemia patients with the MLL-CBP fusion gene.

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Acknowledgements

This work was supported in part by Grants for Cancer Research from the Ministry of Education, Science, Sports and Culture and the Ministry of Health and Welfare, Japan.

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Authors and Affiliations

  1. Saitama Cancer Center Research Institute, Ina-machi, Saitama, 362-0806, Japan

    N Niitsu & Y Honma

  2. First Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan

    N Niitsu

  3. Department of Pediatrics, Faculty of Medicine, University of Tokyo, Tokyo, Japan

    Y Hayashi

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Niitsu, N., Hayashi, Y. & Honma, Y. Downregulation of MLL-CBP fusion gene expression is associated with differentiation of SN-1 cells with t(11;16)(q23;p13). Oncogene 20, 375–384 (2001). https://doi.org/10.1038/sj.onc.1204081

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