CC-90009 treatment reduces leukemic engraftment in AML xenograft models. (A) GSPT1 expression at 24 hours in culture with CC-90009 at indicated concentrations. Each line indicates data relative to 0 nM CC-90009 for an individual patient sample (n = 23). Lines in black, cyan, and red represent samples with >70%, 50% to 70%, and <50% GSPT1 reduction, respectively, at the 100-nM treatment dose. (B) Schematic experimental design for in vivo CC-90009 treatment. IF, intrafemoral transplantation; LDA, limiting dose assay; LSC17, a 17-gene leukemia stem cell signature. (C) Relative GSPT1 degradation to controls in the RF and BM of NOD.SCID mice engrafted with AML and treated with CC-90009 (n = 2-4 mice per treatment group). PR, partial responder; R, responder. (D) CD45⁺CD33⁺ AML engraftment levels in RF and BM of xenotransplanted mice treated with vehicle (dark green bars) or CC-90009 (purple bars) (n = 5 per treatment group). Bars represent mean ± standard error of the mean (SEM) of an individual patient sample. (E) Relative reduction in leukemic engraftment in mice treated with CC-90009 compared with controls, and transplanted with de novo or secondary or relapsed AML, normal or abnormal cytogenetics, MRC adverse or intermediate risk group, and high or low LS17 scores. Each dot represents an individual patient sample. Bars are the median values for each group. For panels C and E, relative change for each patient sample was calculated as (median of CC90009 – median of vehicle)/median of vehicle × 100. *P < .05, **P < .01, ***P < .001, ****P < .0001. ns, not significant.