Fig. 6: A pre-clinical model of near-haploid B-ALL shows in vivo up-regulation of RAD51B and G2/M checkpoint signatures in response to combination chemotherapy.

a Uniform Manifold Approximation and Projection (UMAP) plot of single-cell transcriptomic profiles across PDX leukemia cells in different conditions. BM: bone marrow, SP: spleen. Cells are color-coded according to their treatment groups. b Violin plots showing single-cell expression of a RAD51B signature program in response to combination chemotherapy (red) vs cells treated with vehicle (gray) in a PDX model of near-haploid B-ALL. VXDL: vincristine, dexamethasone, doxorubicin and L-asparaginase. ****: Wilcoxon rank-sum test p-value < 2.2 × 10⁻¹⁶, ***: Wilcoxon rank-sum test p-value = 0.0017. n.s.: Wilcoxon rank-sum test p-value = 0.424. c Left panel: combined UMAP plot of all 11,922 single leukemia cell transcriptomes in the experiment, with cells color-coded according to their labels assigned by unsupervised clustering. Middle (near-haploid B-ALL) and right (diploidized B-ALL) panels: participation of each sample in each of the clusters, shown in colored bars representing percentages. d Violin plots of expression of top 10 (ranked by log2 fold change values) Cluster 2 marker genes in each cluster. e, f Analysis of microarray expression profiles in B-ALL patients showing gross chromosome gains or losses. e PCA plot of individual samples colored by karyotype groups. f Same plot as (e) with individual data points colored by the relative expression of the RAD51B signature. g Violin plots showing normalized RAD51B expression in B-ALL patient samples in each karyotype group. Wilcoxon rank-sum test p-values are labeled between groups. Number of samples in each group: Near-diploid: n = 19, low hypodiploid: n = 17, masked low hypodiploid: n = 6, near-haploid: n = 35, masked near-haploid: n = 17, high hyperdiploid: n = 4, high hypodiploid: n = 1).