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Prolonged molecular remission in PML-RARα-positive acute promyelocytic leukemia treated with minimal chemotherapy followed by maintenance including the histone deacetylase inhibitor sodium valproate

Leukemia volume 19, pages 1676–1677 (2005)Cite this article

TO THE EDITOR

Acute promyelocytic leukemia (APL) is characterized by chromosomal rearrangements involving 17q21 disrupting the gene encoding retinoic acid receptor alpha (RARα), a transcription factor implicated in regulation of normal myelopoiesis. To date, five different fusion partners of RARα have been identified, with PML being most commonly involved as a result of the t(15;17)(q22;q12–21) translocation. In contrast to RARα, which functions as a transcriptional activator at physiological levels of its ligand retinoic acid (RA), the APL-associated fusion proteins act as transcriptional repressors due to preferential binding of corepressor complexes and recruitment of histone deacetylases (HDACs). Treatment of APL blasts harboring the PML-RARα oncoprotein with pharmacological levels of ATRA induces a conformational change in the fusion protein leading to displacement of corepressor complexes in favor of coactivators leading to histone acetylation and transcriptional activation, contributing to relief in the block in myeloid differentiation (reviewed in Mistry et al1).

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Acknowledgements

We are grateful to Fabien Guidez for critical reading of the manuscript and to the Special Trustees of Guy's Hospital for assistance in purchase of ABI7700. EN and molecular studies were supported by Leukaemia Research Fund of Great Britain (0153). We thank Michaela Ward for her assistance with this report and Professor Charles Craddock for interesting discussions.

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Authors and Affiliations

  1. Department of Haematology, University Floor, Belfast City Hospital, Belfast, UK

    M F McMullin & A Thompson

  2. Department of Haematology, C Floor, Belfast City Hospital, Belfast, UK

    M F McMullin & F G C Jones

  3. Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London, UK

    E Nugent & D Grimwade

  4. Department of Haematology, Craigavon Area Hospital, Portadown, Craigavon, UK

    D Hull

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  1. M F McMullin
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Correspondence to D Grimwade.

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McMullin, M., Nugent, E., Thompson, A. et al. Prolonged molecular remission in PML-RARα-positive acute promyelocytic leukemia treated with minimal chemotherapy followed by maintenance including the histone deacetylase inhibitor sodium valproate. Leukemia 19, 1676–1677 (2005). https://doi.org/10.1038/sj.leu.2403883

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