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. 2022 Dec 15;108(7):1768–1781. doi: 10.3324/haematol.2022.281692

Figure 2.

Figure 2.

Comparison of venetoclax sensitivity among different assays and cell culture media. (A) Venetoclax sensitivity of trial participants (n=37) assessed using CellTiterGlo® (CTG) and flow cytometry (FC) assays and expressed as measured by the drug sensitivity score. The line represents the median. The P value was calculated using a two-tailed Wilcoxon matched-pairs signed-rank test. (B) FC scatter plot of a sample treated with dimethylsulfoxide (DMSO) control or 100 nM of venetoclax for 48 h. Blasts, lymphocytes, monocytic cells, and granulocytic cells are gated in the upper row plots using side scatter versus CD45, and in the lower row blasts are gated using CD34. Absolute numbers of viable cells present after treatment with 100 nM of venetoclax in each gate were normalized to the number of cells present in the wells containing the DMSO control. (C) Comparison of sensitivity to venetoclax between samples with blast counts <50% (n=19) and >50% (n=18), assessed using the CTG assay in conditioned medium. The line represents the median. The P value was calculated using the Mann-Whitney U test. (D) Sensitivity to venetoclax of samples with blast counts <50% (n=19), assessed using the CTG or FC assay. The line represents the median. The P value was calculated using a two-tailed Wilcoxon matched-pairs signed-rank test. (E) Blast-specific venetoclax sensitivity measured using FC in three different cell culture media. The line represents the median. The P value was calculated using a two-tailed Wilcoxon matched-pairs signed-rank test. (F) The drug sensitivity scores for venetoclax determined using different assays and media and plotted for each participant (n=37). Participants were divided into responders (n=25) and non-responders (n=12). The line represents the median. The P value was calculated using a one-tailed Mann-Whitney U test. CM: conditioned medium; SSC: side scatter; Gran: granulocytes; Mon: monocytes; Lym: lymphocytes; DSS: drug sensitivity score; RD: refractory disease; PD: progressive disease; CR: complete remission; CRi: complete remission with incomplete blood recovery; MLFS: morphological leukemia-free state; AZA: azacitidine.