Fig. 6: Significant tumor growth delay achieved through effective synergistic dual targeting of PIM kinase and MCL1 in a myeloma xenograft model.

a Tumor progression was monitored weekly with measurement of mice serum human IgL and IgE levels after RPMI8226 and U266 cells engraftment, respectively. Data are shown as mean (n = 4). b Immunostaining of engrafted and contralateral femurs with human CD138 (hCD138) marker at the start and end of the experiment. c Female NSG mice received hydroxyurea prior to transplantation of tumor cells into the right femur. When mean human Ig levels reached 1000 ng/mL, mice were randomized to receive vehicle, AZD1208 alone (oral gavage, daily), AZD5991 only (IV injection, weekly), or both. Blood samples were taken weekly, and femurs were collected at the endpoint for analysis. Created with BioRender.com. d Serum IgL levels were tracked from baseline to 4 weeks following treatment with vehicle, AZD1208 alone, AZD5991 alone, or their combination, normalized to randomization values. Data are shown as mean ± SEM (n = 4). Statistical comparisons were made across all treatment groups. e Flow cytometry analysis of viable hCD138-positive cells in harvested femurs at the endpoint. Data are mean +/− SEM (n = 3). f hCD138 immunostaining of contralateral femurs from mice treated with AZD5991 alone or AZD5991/AZD1208 combination. g Serum IgL levels were tracked from baseline to 5 weeks of treatment with vehicle, AZD1208 alone, AZD5991 alone, or both, normalized to randomization. Data are shown as mean ± SEM (n = 6). Statistical analysis compared the AZD1208 + AZD5991 condition only to AZD1208 alone and AZD5991 alone. P-values were calculated using two-way ANOVA with Sidak’s adjustment for (d) and one-way ANOVA with Dunnett’s adjustment for (g). “n”, denotes the number of distinct mouse samples. Source data are provided as a Source Data file. IgL immunoglobulin light chain lambda.