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. 2020 Feb 6;11:740. doi: 10.1038/s41467-020-14604-6

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© The Author(s) 2020

Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a Heatmap representation of Fraction Affected (FA) and Bliss interaction index across five-point dose range of a BET inhibitor (I-BET151) and a CDK7 inhibitor (THZ1) in K562 and Jurkat cells. Mean values of triple biological experiments were shown. (b and c) Proliferation analysis of K562 and Jurkat cells (b) or murine AF9 AML cells (c) treated with DMSO (black), THZ1 (green), I-BET151 (blue), and the combination of THZ1 + I-BET151 (red). The concentrations of I-BET151 and THZ1 were 2.5 μM and 12.5 nM for K562, 2.5 μM and 3.125 nM for Jurkat, 2.5 μM and 50 nM for murine AF9 AML cells, respectively. Data were shown as mean ± S.D; n = 6 from 3 independent assays, **P = 0.00002 (K562), 0.00009 (Jurkat) and 0.000006 (AF9 resistant), by two-tailed Student’s t test. d, e Immunoblot analysis on apoptosis-related marker PARP and cleaved caspase 3 (C/Caspase3) in K562 (d, top), Jurkat (d, bottom) and murine AF9 AML cells (e) treated with DMSO, THZ1, I-BET151, and the combination of THZ1 + I-BET151. The inhibitor concentrations were the same as shown in Fig. 2b, c. Three independent assays were performed. f, g Quantification of proliferation of K562, Jurkat cells (f) and murine AF9 AML cells (g) transduced with shRNAs targeting CDK7 and/or BRD4. Data were shown as mean ± S.D; n = 8 from three independent assays, **P = 0.00003 (K562), 0.00001 (Jurkat) and 0.000002 (AF9 resistant), by two-tailed Student’s t test.