Synergistic anti-tumor effects of eltanexor and venetoclax in primary AML and DLBCL samples ex vivo and in an AML patient-derived xenograft. AML and DLBCL mononuclear cells were treated ex vivo with threefold dilutions of eltanexor, venetoclax, or eltanexor-venetoclax combined for 48 hours. The viability of treated cells compared with DMSO control using the CellTiter-Glo assay was plotted for the indicated concentrations. Viability was significantly decreased after 48 hours of treatment with combined eltanexor-venetoclax in DLBCL (A) or AML (B) cells. (C) Apoptosis was measured in AML or normal (NML) blast cells (SSC^lo/CD45^mid/CD33⁺) by AnnV/PI staining using flow cytometry after 24 hours of treatment. The percent of live cells (AnnV^–/PI^–) relative to DMSO was measured. Data are expressed as mean ± SEM. Individual patients are represented by specific shapes in panels A-C, and individual AML patients who were venetoclax-responsive (orange) or primary induction refractory (lavender) in the clinic are represented by colored symbols in panels B and C. (D-E) An AML patient-derived xenograft model was used to test the in vivo effects of treatment with eltanexor, venetoclax, or eltanexor-venetoclax combined compared with vehicle. (D) Percentage of hCD45⁺ cells in the PB from day 28 to day 93 posttransplantation. The data represent the mean of 5 mice per cohort ± SEM. *P < .05 and ***P < .001, compared with vehicle at day 93. (E) Percentage of hCD45⁺ cells in the bone marrow and spleen tissues at day 93 posttransplantation. The data represent the mean of 5 mice per cohort ± SEM. (F) Representative immunohistochemical staining of bone marrow and spleen sections for expression of hCD45 from mice with AML patient-derived xenografts in panels D and E. Scale bar, 20 µm. Histology images were acquired with an Olympus BX43F microscrope at 40× magnification. *P < .05; **P < .01; ****P < .0001.