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. 2020 Jul 20;11:3639. doi: 10.1038/s41467-020-17336-9

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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. 7 — a Correlation analysis (Supplementary Methods) identified AK1 protein expression to be strongly negatively correlated with response to antimetabolite drugs including Zalcitabine and Nelarabine. b AK1 expression (left panel) and drug-sensitivity analysis of Zalcitabine, Nelarabine and Cytarabine in the NCI60 panel (right three panels; n = 59 cell lines). Cell lines are colored by tissue of origin as in Fig. 1. c Quantification of antimetabolites by multiple reaction monitoring (Supplementary Methods) in their active nucleotide triphosphate form (NTP) showing that AK1 decreases NTP abundance significantly in vitro (t-test; P < 0.05; ara-CTP = Cytarabine; ara-GTP = Nelarabine; ddCTP = Zalcitabine; dfCTP = Gemcitabine). ATP served as a positive control. Error bars represent the standard deviation of three biological replicates. d Western blot confirming successful overexpression of AK1 in Jurkat cells (Supplementary Methods). e AK1 overexpression (red) in combination with Cytarabine treatment in Jurkat cells resulted in significantly reduced apoptosis in a concentration- and time-dependent manner (time-point-wise t-test, P < 0.05). The width of blue and red lines represents the range of relative apoptosis across three technical replicates. f Kaplan–Meier analysis of AML patients stratified by AK1 expression. Patients with low AK1 expression (blue) survive significantly longer than patients with high AK1 expression (red; log-rank test, P < 0.0001). The number of patients at risk is shown below the Kaplan–Meier plot. Source data are provided as a Source Data file.