Fig. 1: Drug response profiling exposes differential dependencies of DLBCL and other lymphoma cell lines on pathways that are commonly deregulated in hematological malignancies. | Leukemia

Fig. 1: Drug response profiling exposes differential dependencies of DLBCL and other lymphoma cell lines on pathways that are commonly deregulated in hematological malignancies.

From: Inhibitors of Bcl-2 and Bruton’s tyrosine kinase synergize to abrogate diffuse large B-cell lymphoma growth in vitro and in orthotopic xenotransplantation models

Fig. 1

a Heat map displaying the viability (calculated as the mean of the five concentrations assessed per drug) of 19 cell lines of the indicated entities, as assessed by CellTiter-Glo viability assay, after 48 h of exposure to 126 manually selected compounds targeting deregulated pathways in hematological malignancies. Select compounds with differential effects on viability are indicated. Five concentrations, generated by serial (fivefold) dilution, were tested per compound. See Supplementary Table 1 for the compounds and their respective highest concentrations. MCL, mantle cell lymphoma; BL, Burkitt lymphoma. Select compounds are indicated in red. b Heat map showing the viability of the subgroup of DLBCL cell lines only, and their differential responses to the indicated compounds. Cell lines are color-coded based on cell-of-origin (ABC-DLBCL in red, GCB-DLBCL in green, unclassified in black). c Viability curves, derived from the drug screen, of the indicated cell lines, showing all five assessed concentrations and three drugs targeting AKT signaling (ipatasertib), Bcl-2 (venetoclax), and dihydrofolate reductase (methotrexate). d Validation of viability after 48 h of exposure to the same three compounds, as assessed individually by CellTiter-Blue assay. Means ± standard deviations are shown for two to three independent experiments per cell line and drug, each quantified in duplicate measurements. e Competitive proliferation assay, performed over a period of 24 days, of the four indicated cell lines subjected to CRISPR-based editing of the BCL2 locus, the RPA locus as positive control representing an essential gene, and a control guide RNA. Successfully targeted cells were identified by their blue fluorescent protein (BFP) expression and mixed 1:1 with non-edited cells at the start of the experiment. Two different guide RNAs are shown for Bcl-2. Data in e are representative of three independent experiments.

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