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. 2020 May 25;12:73. doi: 10.1186/s13148-020-00860-2

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 2 — Combination of hDot1L inhibitors with other agents. EPZ-5676 (DOT1L inhibitor) in conjunction with standard of care drugs for AML (cytarabine and daunorubicin) and DNA hypomethylating agents (azacitidine and decitabine) showed synergistic antiproliferative effect against MLL-rearranged leukemic cells. Monotherapy involving only hDot1L inhibitors showed only modest effect as indicated by single arrows in case of EPZ-5676 and EPZ004777. Moreover, another inhibitor of hDot1L (EPZ004777) in combination with MLL-Menin interaction inhibitor (MI-2-2) also showed synergistic growth inhibitory effects in the MLL-rearranged leukemias. The synergistic therapeutic effect is denoted by small multiple arrows in cases involving combined treatment