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Epigenetic targeting of Notch1-driven transcription using the HDACi panobinostat is a potential therapy against T-cell acute lymphoblastic leukemia

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  1. 1

    Pui CH, Robison LL, Look AT . Acute lymphoblastic leukaemia. Lancet 2008; 371: 1030–1043.

    CAS  Article  Google Scholar 

  2. 2

    Weng AP, Ferrando AA, Lee W, JPt Morris, Silverman LB, Sanchez-Irizarry C et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 2004; 306: 269–271.

    CAS  Article  Google Scholar 

  3. 3

    Sanda T, Li X, Gutierrez A, Ahn Y, Neuberg DS, O'Neil J et al. Interconnecting molecular pathways in the pathogenesis and drug sensitivity of T-cell acute lymphoblastic leukemia. Blood 2010; 115: 1735–1745.

    CAS  Article  Google Scholar 

  4. 4

    Roderick JE, Tesell J, Shultz LD, Brehm MA, Greiner DL, Harris MH et al. c-Myc inhibition prevents leukemia initiation in mice and impairs the growth of relapsed and induction failure pediatric T-ALL cells. Blood 2014; 123: 1040–1050.

    CAS  Article  Google Scholar 

  5. 5

    Bolden JE, Peart MJ, Johnstone RW . Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 2006; 5: 769–784.

    CAS  Article  Google Scholar 

  6. 6

    Dickinson M, Johnstone RW, Prince HM . Histone deacetylase inhibitors: potential targets responsible for their anti-cancer effect. Investig New Drugs 2010; 28: S3–20.

    Article  Google Scholar 

  7. 7

    Lindemann RK, Newbold A, Whitecross KF, Cluse LA, Frew AJ, Ellis L et al. Analysis of the apoptotic and therapeutic activities of histone deacetylase inhibitors by using a mouse model of B cell lymphoma. Proc Natl Acad Sci USA 2007; 104: 8071–8076.

    CAS  Article  Google Scholar 

  8. 8

    Vilas-Zornoza A, Agirre X, Abizanda G, Moreno C, Segura V, De Martino Rodriguez A et al. Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia. Leukemia 2012; 26: 1517–1526.

    CAS  Article  Google Scholar 

  9. 9

    Peart MJ, Smyth GK, van Laar RK, Bowtell DD, Richon VM, Marks PA et al. Identification and functional significance of genes regulated by structurally different histone deacetylase inhibitors. Proc Natl Acad Sci USA 2005; 102: 3697–3702.

    CAS  Article  Google Scholar 

  10. 10

    Marshall GM, Gherardi S, Xu N, Neiron Z, Trahair T, Scarlett CJ et al. Transcriptional upregulation of histone deacetylase 2 promotes Myc-induced oncogenic effects. Oncogene 2010; 29: 5957–5968.

    CAS  Article  Google Scholar 

  11. 11

    Aster JC, Xu L, Karnell FG, Patriub V, Pui JC, Pear WS . Essential roles for ankyrin repeat and transactivation domains in induction of T-cell leukemia by notch1. Mol Cell Biol 2000; 20: 7505–7515.

    CAS  Article  Google Scholar 

  12. 12

    Hawkins ED, Duarte D, Akinduro O, Khorshed RA, Passaro D, Nowicka M et al. T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments. Nature 2016; 538: 518–522.

    Article  Google Scholar 

  13. 13

    Waibel M, Christiansen AJ, Hibbs ML, Shortt J, Jones SA, Simpson I et al. Manipulation of B-cell responses with histone deacetylase inhibitors. Nat Commun 2015; 6: 6838.

    CAS  Article  Google Scholar 

  14. 14

    Richardson PG, Schlossman RL, Alsina M, Weber DM, Coutre SE, Gasparetto C et al. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood 2013; 122: 2331–2337.

    CAS  Article  Google Scholar 

  15. 15

    Heinzel S, Binh Giang T, Kan A, Marchingo JM, Lye BK, Corcoran LM et al. A Myc-dependent division timer complements a cell-death timer to regulate T cell and B cell responses. Nat Immunol 2017; 18: 96–103.

    CAS  Article  Google Scholar 

  16. 16

    Tan D, Phipps C, Hwang WY, Tan SY, Yeap CH, Chan YH et al. Panobinostat in combination with bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma: an open-label, multicentre phase 2 trial. Lancet Haematol 2015; 2: e326–e333.

    Article  Google Scholar 

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The work was funded by the Australian National Health and Medical Research Council. MW was supported by a fellowship from the Deutsche Forschungsgemeinschaft and funding from the NHMRC. SJV was funded by a Rubicon fellowship from the Netherlands Organization for Scientific Research. EDH was supported by a fellowship from the National Health and Medical Research Council of Australia. RWJ was supported by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship, project and program grants from the NHMRC, the Cancer Council Victoria and the Victorian Cancer Agency. EDH would like to thank Sarah Russell for mentorship through the project.

Author contributions

MW, SJV, SH, EDH and RWJ designed the experiments. MW, SJV, IYK, BPM, KMR and EDH performed the experiments. MW, SJV, IYK, BPM, KMR and EDH analyzed the data. MW, SJV, EDH and RWJ wrote the manuscript.

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Corresponding authors

Correspondence to E D Hawkins or R W Johnstone.

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Competing interests

The Johnstone laboratory receives research funding from Novartis for studies involving panobinostat.

Additional information

Supplementary Information accompanies this paper on the Leukemia website

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Waibel, M., Vervoort, S., Kong, I. et al. Epigenetic targeting of Notch1-driven transcription using the HDACi panobinostat is a potential therapy against T-cell acute lymphoblastic leukemia. Leukemia 32, 237–241 (2018).

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