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Acute Leukemias

TAL1/SCL is downregulated upon histone deacetylase inhibition in T-cell acute lymphoblastic leukemia cells

Leukemia volume 25, pages 1578–1586 (2011)Cite this article

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Abstract

The transcription factor T-cell acute lymphocytic leukemia (TAL)-1 is a major T-cell oncogene associated with poor prognosis in T-cell acute lymphoblastic leukemia (T-ALL). TAL1 binds histone deacetylase 1 and incubation with histone deacetylase inhibitors (HDACis) promotes apoptosis of leukemia cells obtained from TAL1 transgenic mice. Here, we show for the first time that TAL1 protein expression is strikingly downregulated upon histone deacetylase inhibition in T-ALL cells. This is due to decreased TAL1 gene transcription in cells with native TAL1 promoter, and due to impaired TAL1 mRNA translation in cells that harbor the TAL1d microdeletion and consequently express TAL1 under the control of the SCL/TAL1 interrupting locus (SIL) promoter. Notably, HDACi-triggered apoptosis of T-ALL cells is significantly reversed by TAL1 forced overexpression. Our results indicate that the HDACi-mediated apoptotic program in T-ALL cells is partially dependent on their capacity to downregulate TAL1 and provide support for the therapeutic use of HDACi in T-ALL.

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Acknowledgements

We are grateful to the patients and their families who have generously contributed to this study. We thank Dr Nuno R dos Santos for kindly providing the PF382 cell line used in this study. This work was supported by grants from Children with Leukaemia Charity, UK, and from Fundação para a Ciência e a Tecnologia, FCT, Portugal (PTDC/SAU-OBD/69974 and 104816); BAC and SFdA had FCT SFRH PhD and postdoctoral fellowships, respectively. ABAL had a PhD fellowship from FAPESP.

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Authors and Affiliations

  1. Cancer Biology Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal

    B A Cardoso & J T Barata

  2. Cell Biology Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal

    S F de Almeida & M Carmo-Fonseca

  3. Laborat,

    A B A Laranjeira & J A Yunes

  4. ó,

    A B A Laranjeira & J A Yunes

  5. rio de Biologia Molecular, Centro Infantil Boldrini, Campinas, São Paulo, Brazil

    A B A Laranjeira & J A Yunes

  6. Department of Cell Biology, University Medical Centre, Utrecht, The Netherlands

    P J Coffer

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Cardoso, B., de Almeida, S., Laranjeira, A. et al. TAL1/SCL is downregulated upon histone deacetylase inhibition in T-cell acute lymphoblastic leukemia cells. Leukemia 25, 1578–1586 (2011). https://doi.org/10.1038/leu.2011.140

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