Figure 6.
Primary NUP98r xenograft cells are vulnerable to JAK-STAT signaling inhibitors. (A) Schematic overview of the procedures used to perform the cell surface proteomic analysis of CD41+ AMKL cells isolated from the spleen of NUP98r (NUP98-BPTF) PDX mice. Cell surface proteins were biotinylated and isolated using streptavidin pulldown and stringent washes. Analysis by liquid chromatography-mass spectrometry allowed for identification of 411 cell surface proteins, including AMKL-specific biomarkers (supplemental Table 9). (B) Top 10 hallmark gene sets enriched in the analysis of the cell surface proteins detected on NUP98r AMKL primary xenograft using Metascape (see supplemental Methods for details). The complete analysis is provided in supplemental Table 10. (C) Dose-response curves and half maximal inhibitory concentrations (IC50) determined for each indicated cell type submitted to a viability assay in presence of an inhibitor or DMSO vehicle (Cell-Titer Glo, 6-day incubation). Experiments were conducted with 4 replicates. CMK, N5A xAMKL (E771, G662), and CB-CD34+ (no. 5/6 and 7); n = 1 experiment. M07e, ML-2, 2ary NTF AMKL PDX (I603, I604); n = 2 experiments.

Primary NUP98r xenograft cells are vulnerable to JAK-STAT signaling inhibitors. (A) Schematic overview of the procedures used to perform the cell surface proteomic analysis of CD41+ AMKL cells isolated from the spleen of NUP98r (NUP98-BPTF) PDX mice. Cell surface proteins were biotinylated and isolated using streptavidin pulldown and stringent washes. Analysis by liquid chromatography-mass spectrometry allowed for identification of 411 cell surface proteins, including AMKL-specific biomarkers (supplemental Table 9). (B) Top 10 hallmark gene sets enriched in the analysis of the cell surface proteins detected on NUP98r AMKL primary xenograft using Metascape (see supplemental Methods for details). The complete analysis is provided in supplemental Table 10. (C) Dose-response curves and half maximal inhibitory concentrations (IC50) determined for each indicated cell type submitted to a viability assay in presence of an inhibitor or DMSO vehicle (Cell-Titer Glo, 6-day incubation). Experiments were conducted with 4 replicates. CMK, N5A xAMKL (E771, G662), and CB-CD34+ (no. 5/6 and 7); n = 1 experiment. M07e, ML-2, 2ary NTF AMKL PDX (I603, I604); n = 2 experiments.

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