Multi-parametric single cell evaluation defines distinct drug responses in healthy hematological cells that are retained in corresponding malignant cell types.

Multi-parametric single cell evaluation defines distinct drug responses in healthy hematological cells that are retained in corresponding malignant cell types. Haematologica. 2019 Aug 22;: Authors: Majumder MM, Leppä AM, Hellesøy M, Dowling P, Malyutina A, Kopperud R, Bazou D, Andersson E, Parsons A, Tang J, Kallioniemi O, Mustjoki S, O'Gorman P, Wennerberg K, Porkka K, Gjertsen BT, Heckman CA Abstract Innate drug sensitivity in healthy cells aids identification of lineage specific anti-cancer therapies and reveals off-target effects. To characterize the diversity in drug responses in the major hematopoietic cell types, we simultaneously assessed their sensitivity to 71 small molecules utilizing a multi-parametric flow cytometry assay and mapped their proteomic and basal signaling profiles. Unsupervised hierarchical clustering identified distinct drug responses in healthy cell subsets based on their cellular lineage. Compared to other cell types, CD19+/B and CD56+/NK cells were more sensitive to dexamethasone, venetoclax and midostaurin, while monocytes were more sensitive to trametinib. Venetoclax exhibited dose dependent cell selectivity that inversely correlated to STAT3 phosphorylation. Lineage specific effect of midostaurin was similarly detected in CD19+/B cells from healthy, acute myeloid leukemia and chronic lymphocytic leukemia samples. Comparison of drug responses in healthy and neoplastic cells showed that healthy cell r...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research