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HDAC3 activity is required for initiation of leukemogenesis in acute promyelocytic leukemia

Leukemia volume 31, pages 995–997 (2017)Cite this article

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The classical definition of oncogenes and oncosuppressors has been modified by the experimental observation that the same gene can play dramatically distinct functions at different stages of tumorigenesis (initiation vs maintenance).

Studying the molecular pathogenesis of Acute Promyelocytic Leukemia (APL), we found that histone deacetylases (HDACs) are associated with the initiating oncogenic fusion protein PML-RARα, thus suggesting an oncogenic role for HDACs. In established APL leukemic cells, knockdown of HDACs 1/2/3 slows down leukemia growth, consistent with an oncogenic role at this stage.1, 2 In contrast, knockdown of HDAC1/HDAC2 in PML-RARα transgenic mice accelerates leukemia development, showing that HDAC1/HDAC2 can play an oncosuppressive role in leukemia initiation. These findings have then been extended to other tumor subtypes, including: (i) monoclonal lymphoblastic thymic lymphomas in which a dosage-dependent tumor suppressive role has been found for HDAC1 and HDAC2;3 (ii) gastric, breast, prostate and colon cancer, where HDAC1 has an oncogenic role; (iii) colorectal cancer, where HDAC2 can function as an oncogene.4

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Acknowledgements

Work in SM’s lab was supported by EC (4D Cell Fate), AIRC (IG13), CNR (Epigen Flagship Project). PM was a recipient of Fondazione Italiana per la ricerca sul cancro (FIRC) fellowship. We thank Roberto Dal Zuffo, Isabella Pallavicini and Alessia Schirripa for technical assistance.

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Author notes

  1. P Mehdipour and F Santoro: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Experimental Oncology, European Institute of Oncology, Milan, Italy

    P Mehdipour, F Santoro, M Romanenghi, C Pagliuca & S Minucci

  2. Division of Experimental Oncology, Functional Genomics of Cancer Unit, San Raffaele Scientific Institute, Milan, Italy

    O A Botrugno

  3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    G M Matthews

  4. Gene Regulation Laboratory, Cancer Therapeutics Program, Peter MacCallum Cancer Institute, St Andrews Place, Victoria, Australia

    R W Johnstone

  5. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia

    R W Johnstone

  6. Department of Biosciences, University of Milan, Milan, Italy

    S Minucci

Authors
  1. P Mehdipour
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  2. F Santoro
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  3. O A Botrugno
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  4. M Romanenghi
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  5. C Pagliuca
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  6. G M Matthews
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  7. R W Johnstone
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  8. S Minucci
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Corresponding authors

Correspondence to F Santoro, R W Johnstone or S Minucci.

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The authors declare no conflict of interest.

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Mehdipour, P., Santoro, F., Botrugno, O. et al. HDAC3 activity is required for initiation of leukemogenesis in acute promyelocytic leukemia. Leukemia 31, 995–997 (2017). https://doi.org/10.1038/leu.2017.3

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