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Cell lines from hematologic cancers, including multiple myeloma (MM), AML, and DLBCL, exhibit a strong dependency on MCL1 for survival. Cell lines from.

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Presentation on theme: "Cell lines from hematologic cancers, including multiple myeloma (MM), AML, and DLBCL, exhibit a strong dependency on MCL1 for survival. Cell lines from."— Presentation transcript:

1 Cell lines from hematologic cancers, including multiple myeloma (MM), AML, and DLBCL, exhibit a strong dependency on MCL1 for survival. Cell lines from hematologic cancers, including multiple myeloma (MM), AML, and DLBCL, exhibit a strong dependency on MCL1 for survival. A, Profile of response to AM-8621 for 952 tumor–derived cell lines grouped by cancer subtype. SCC, squamous cell carcinoma; BCL, B-cell lymphoma; SCLC, small cell lung cancer. Top plot, cell line count; middle plot, distribution of maximum drug effect on cell viability (Emax); bottom plot, median IC50 (natural logarithm of μmol/L values). Effects on cell viability were measured by resazurin assay. B, Relative sensitivity of cancer subtypes and statistical enrichment for sensitive cell lines. The volcano plot reports sensitivity to AM-8621 versus statistical significance [-log P value of the Fisher exact test performed using a 10 μmol/L threshold (maximum tolerated dose)] for classification into sensitive and resistant cell lines. Among all individual cancer subtypes included in viability screen, those that demonstrated statistically significant enrichments are shown. T-ALL, T-cell acute lymphoblastic leukemia; B-ALL, B-cell acute lymphoblastic leukemia. C, Effects of AM-8621 treatment on the viability of expanded panels of MM (n = 19), AML (n = 28), and DLBCL (n = 21) cell lines. Effects on cell viability were measured by CellTiter-Glo. Mean values from n = 2 to 5 biological replicates for individual cell lines. Black bars report mean and ±SD across indication. D, Comparison of sensitivity to AM-8621 versus venetoclax across MM, AML, and DLBCL cell line panels. E, Relationship between BCL-xL RNA expression and sensitivity to AM-8621 for those MM cell lines (n = 14) reported in Fig. 4C and D for which BCL-xL FPKM values were available from the Cancer Cell Line Encyclopedia (42). Sean Caenepeel et al. Cancer Discov 2018;8: ©2018 by American Association for Cancer Research

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