Figure 7.

Systematic comparison of drug responses in healthy cell-of-origin and corresponding cell types from hematologic malignancies. (A-F) Ex vivo drug responses presented as drug sensitivity scores (DSS) of healthy cell types (CD3, n=4; CD14, n=4; CD19, n=2; CD34, n=2; and CD138, n=3) were compared to malignant counterparts in a cohort of 281 primary samples for bortezomib, clofarabine, dexamethasone, omipalisib, venetoclax and navitoclax. Samples included both published and unpublished datasets generated at our facility for chronic myeloid leukemia (CML) (n=13),^10,11 chronic myelomonocytic leukemia (CMML) (n=11),¹² myelodysplastic syndromes (MDS) (n=4), acute myeloid leukemia (AML) (n=145),^9,12 B-cell acute lymphoblastic leukemia (B-ALL) (n=14),¹³ chronic lymphocytic leukemia (CLL) (n=4),¹² T-cell prolymphocytic leukemia (T-PLL) (n=40),¹⁴ multiple myeloma (MM) (n=50)¹⁵ and other hematologic malignancies (n=6). AML and MM samples were subdivided depending on whether they were derived from newly diagnosed (D) and relapsed (R) samples. T-PLL and MM samples were tested with enriched CD8⁺ and CD138⁺ cells. Results provide evidence that response in healthy cell subsets is predictive of responses observed in the malignant cell counterparts. A comparison between drug effects on CD14⁺ and CD34⁺ cells derived from healthy individuals and AML samples are displayed in Online Supplementary Figure S13 and S14. B-PLL: B-cell prolymphocytic leukemia.