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. 2024 Jan 2;15:32. doi: 10.1038/s41467-023-44137-7

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© The Author(s) 2024

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

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Fig. 4 — a AML bone marrow aspirates for single cell RNA sequencing (scRNA-seq) were obtained from participants in the ETCTN/CTEP 10026 study, which tested combined decitabine and ipilimumab in advanced MDS/AML or relapsed AML post-HSCT patients. Samples were analyzed at study entry (screening) and time of response. b Percentage of donor-derived cells across bone marrow associated immune cell types across 8 AML cases re-analyzed from Penter et al., Blood 2023²⁴ using souporcell (left). Percentage of genotyped cells with AML-associated somatic mutation for bone marrow-associated hematopoietic cell types across 9 AML cases (right). Cell types from scRNA-seq profiles were identified using short-read sequencing and reference-based annotations (UMAP top). Recurrently mutated genes were amplified and sequenced using nanoranger to identify leukemic cell compartments and immune cells with recurrent AML-associated mutations (UMAP bottom). c Detection of recurrent somatic mutations at screening and at time of response in 5 study participants of ETCTN/CTEP 10026 across HSC (n = 847), LMPP (n = 1,198), GMP (n = 154), megakaryocytic (MK) (n = 815) and erythroid (Ery) (n = 3,223) cells. d Heatmap of somatic mutations (DNMT3A^V296M, TP53^C176S, TP53^R282W), chromosomal aberrations (amp(1p), del(3p), del(5q)) visualized as joint posterior probability calculated with numbat, protein expression and gene expression in AML8007 at screening and at time of response (marrow CR with HI—bone marrow complete remission with hematologic improvement). e Illustration of likely subclonal structure of AML8007 derived from (d) as fish plot with high (magenta) and low (blue) sensitivity to decitabine and ipilimumab. Expression of erythroid (f) and megakaryocytic (g) signature in 646 Beat AML bulk RNA-seq profiles of AML/MDS subtypes. Boxes represent the interquartile range (IQR) from the 25th to 75th percentile and the median value indicated by the inner horizontal line. Whiskers extend to the extreme values but no more than 1.5xIQR above/below the hinge.