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Molecular targets for therapy

Reinstated p53 response and high anti-T-cell leukemia activity by the novel alkylating deacetylase inhibitor tinostamustine

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Fig. 1: Principle of (H)DAC inhibition combined with DNA damage induction in a single agent reinstates p53 activation and reduces T-PLL cell survival.
Fig. 2: Anti-leukemic efficacy of EDO-S101 in vivo.

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  • 23 October 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Acknowledgements

MH is funded by the German Research Foundation (DFG) as part of the collaborative “CONTROL-T” research consortium on mature T-cell lymphomas (FOR1961; HE3553/4-2). Further support to MH: CECAD, CMMC, German José Carreras Leukemia Foundation (DJCLS; R12/08), Fritz Thyssen foundation (10.15.2.034MN), and the DFG KFO-286 (HE-3553/3-2). AS is funded by a scholarship through the DJCLS (03F/2016). AS and MH receive joint support by the DFG (SCHR1668/1-1). TB is funded by the Köln Fortune Program. The European Union supports MH as part of the Transcan-II initiative (ERANET-PLL) as well as MH, SM, and TA as part of EraPerMed JAKSTAT-TARGET. TA is funded by Academy of Finland (grants 279163, 310507, 326238), Cancer Society of Finland (TA). SM is supported by ERC CoG grant (M-IMM), Academy of Finland and Finnish Cancer Organizations. EDO-S101 and research support were provided by Mundipharma EDO GmbH. Open access funding provided by Projekt DEAL.

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Design and experimental data analysis: MH, AS, SP; experiments: SP, AS, LV, PM, NR, JJ, TB, ST, SO, SN, SM, HK; biostatistics: AK, TA; patient samples: MH, M-HS; manuscript preparation: SP, AS, and MH.

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Correspondence to M. Herling.

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Pützer, S., Varghese, L., von Jan, J. et al. Reinstated p53 response and high anti-T-cell leukemia activity by the novel alkylating deacetylase inhibitor tinostamustine. Leukemia 34, 2513–2518 (2020). https://doi.org/10.1038/s41375-020-0772-6

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