Lineage infidelity with an emphasis toward myeloid lineages detected in the DUX4-r blast population. (A) Cell type classification of the BCP-ALL blast cell population. DUX4-r ALL cases with only a minority of cells classified as pro-B cells (heterogeneous blast population) are grouped together on the left. (B) Cell surface protein expression in the predicted cell types, as determined by scADT-seq within the blast population of DUX4-r-1. (C) Volcano plot representing differentially expressed genes between the blast population of DUX4-r ALL samples with heterogeneous blast population (yellow) and homogeneous blast population (green). The P value cutoff is .01. (D) Chromatin accessibility of the gene regions of FLT3 and CEBPA in monocytes, progenitor B cells, DUX4-a, DUX4-b, and other ALL subtype blast cells (BCR::ABL1⁺, ETV6::RUNX1⁺, and HeH ALL). (E) (Upper figure) UMAP visualization of normal GMPs, normal monocytes, monocyte-like blast cells, and lymphoid blast cells from the samples NBM-MNCs and DUX4-r-1, respectively, colored by cell type. (Lower figure) UMAP visualization of GMPs, monocyte-like blast cells, and lymphoid blast cells from the sample DUX4-r-1 only, colored by the presence of the blast cell clonotypic V(D)J rearrangement. (F) Expression of the cell surface markers CD45, CD33, and CD371 vs CD19 on all single cells in the individual case of DUX4-1 ALL, as determined by scADT-seq. Cells are colored by cell type. (G) T-cell–associated cell surface marker CD2 expression on BCP-ALL blast cells and other cell types, as determined by scADT-seq.