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. 2023 Oct 2;4(12):1648–1659. doi: 10.1038/s43018-023-00645-5

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© The Author(s) 2023

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. 4 — a, Overview of the validation cohort. The inner circle represents ELN-22 risk groups in total numbers, and the outer circle represents the distribution of in vivo responders and non-responders in ELN-22 risk groups. b, Ex vivo treatments with significantly different responses in in vivo responders (n = 47) and non-responders (n = 48). Negative log₁₀ (P value) of Student’s t-tests is shown on the y axis, and mean difference between responders and non-responders is on the x axis. The dashed line represents the 10% false discovery rate cutoff (Benjamini–Hochberg procedure); NS, not significant. c, Viability (AUC) after ex vivo treatment with vincristine (top) and viability (volume under the curve (VUC)) after treatment with daunorubicin and cytarabine (bottom) separated by ELN-22 risk groups (ELN-22 adverse risk: non-responder: n = 28, responder: n = 8; ELN-22 intermediate risk: non-responder: n = 14, responder: n = 29; ELN-22 favorable risk: non-responder: n = 6, responder: n = 10). P values are derived from two-sided Student’s t-tests. Centers, hinges and whiskers of the box plots signify medians, quartiles and 1.5× IQR, respectively. d, Kaplan–Meier plots for EFS stratified by ex vivo drug response to vincristine and daunorubicin + cytarabine. For visualization purposes, participant groups of ex vivo responders and weak responders were defined by ex vivo drug responses dichotomized using maximally selected log-rank statistics to visualize effects. Sixty-four of 95 participants were classified as vincristine weak responders. Sixty of 95 participants were classified as daunorubicin + cytarabine weak responders. P values are from two-sided Wald tests on Cox regression models using drug responses as continuous variables. e, Forest plot of hazard ratios in multivariate Cox proportional hazards models for EFS including ELN-22 risk groups and viability after ex vivo treatment with vincristine (top) and daunorubicin + cytarabine (bottom). The ex vivo responses (AUC values) were centered by mean and scaled by 2 s.d. to bring them to a similar scale as the categorical ELN-22 risk group variables.

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