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. 2020 Feb 26;5:17. doi: 10.1038/s41392-020-0112-3

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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 — Transient Mcl-1 downregulation by voruciclib enhances apoptosis induced by venetoclax in AML cells. a, b THP-1 and MV4–11 cells were treated with venetoclax (VEN) and voruciclib (VOR) or flavopiridol (FLV), alone or in combination, for the indicated times. Whole-cell lysates were subjected to western blotting and probed with the indicated antibodies. Relative densitometry measurements were determined using Odyssey Software V3.0 and compared to the control and normalized to β-actin. c MV4–11 and THP-1 cells were treated with venetoclax or voruciclib, alone or combined, for 6 or 24 h. RNA was extracted with TRIzol and subjected to real-time RT‐PCR analysis and normalized to 18S rRNA. ***p < 0.001 compared to control, while ^###p < 0.001 compared to individual drug treatment. d, f, g THP-1 and MV4–11 AML cell lines, primary AML patient samples, and normal peripheral blood mononuclear cells (PBMCs) were treated with venetoclax and voruciclib, alone or in combination, for 6 h and then subjected to Annexin V-FITC/PI staining and flow cytometry analyses. ***p < 0.001 compared to individual drug treatment. CI values were calculated using CompuSyn software. e MV4–11 and THP-1 cells were treated with venetoclax and voruciclib, alone or in combination, for 6 h. Whole-cell lysates were subjected to western blotting and probed with the indicated antibodies. # indicates a nonspecific band