Figure 6.
Cell populations in monocytic acute myeloid leukemia samples have distinct drug response paterns and gene expression profiles. (A) Drug sensitivity score of five myelomonocytic/monocytic samples measured using CellTiterGlo® or flow cytometry assays in conditioned medium. Clinical responses (complete remission/complete remission with incomplete blood recovery/resistant disease) are annotated in the graph. The P value was calculated using a two-tailed Wilcoxon matched-pairs signed-rank test. (B) Uniform Manifold Approximation and Projection (UMAP) representation of monocytic and progenitor cells from three bone marrow samples profiled by single-cell RNA sequencing. The samples were taken from three patients with acute myeloid leukemia before venetoclax-azacitidine treatment. The bar plot on the right shows the proportion of cell phenotypes in each sample. (C) Expression of a set of canonical markers used to identify monocytic and progenitor cell populations. Expression of BCL2 family genes and genes associated with response to venetoclax based on preclinical studies. Dot size corresponds to the percentage of cells expressing a given gene in a given cluster, and dot color corresponds to the average expression of a given gene in a given cluster. Circled dots are differentially expressed in the cluster (Padj<0.05, Bonferroni corrected t test). The clusters are the same as shown in panel (B), and their distributions across patients are shown in the bar plot on the right. DSS: drug sensitivity score; AML: acute myeloid leukemia; CM: conditioned medium; CTG: CellTiterGlo®; sAML: secondary AML; CR: complete remission; CRi: complete remission with incomplete blood recovery; RD: resistant disease; FAB: French-American-British; HPSC: hematopoietic stem and progenitor cell; GMP: granulocyte-monocyte progenitor; Pro-mono: pro-monocyte; DC: dendritic cells; BCL2: BCL2 family gene; Venetoclax: genes associated with venetoclax resistance based on preclinical studies.