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. 2020 Dec 1;35(7):1933–1948. doi: 10.1038/s41375-020-01095-z

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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. 8 — a Inhibition of miR-10a markedly improved the survival of mice bearing OCI-AML3 xenografts compared to the control inhibitor group when treated with both Nutlin-3a (upper left; mean survival 34.6 days vs 22.9 days; p < 0.001) and cytarabine (upper right; mean survival 33.2 days vs 27.4 days; p = 0.02), as visualized in Kaplan–Meier survival plots. A combination of cytarabine, Nutlin-3a, and miR-10a inhibition further increased survival (mean 37.1 days) compared to vehicle-only (mean 22.3 days) and cytarabine + control inhibitor “standard-of-care” controls (lower left; mean 27.4 days; p < 0.001; also see Supplementary Table 4 for pairwise Cox regression comparison p values). Lower right shows mean survival for each treatment group expressed as a fold-change versus vehicle control. Addition of the miR-10a inhibitor significantly increased survival in mice treated with Nutlin-3a (p < 0.001), cytarabine (p = 0.02), and Nutlin-3a + cytarabine (p < 0.001). b This corresponded with significantly reduced hCD45+ leukemic cell infiltrate in the spleen following 7 days of treatment. c Consistent with in vitro findings, while variable, miR-10a inhibited AML cells exhibited a trend towards lower MDC-positivity, indicating a repressed autophagy response (p = 0.21). Images were collected using a Leica Aperio LV1 Real-time Digital Pathology System (20× scan). (*p < 0.05, **p < 0.01; ***p < 0.001 by Student’s T test with error bars representing SD (six 400–600-cell fields quantified per bar)).