S63845 exerts no enduring toxicity in the huMcl-1 mouse model at the MTD. (A) Kaplan-Meier survival curves of huMcl-1 or wild-type mice treated for 5 consecutive days with vehicle or increasing doses of S63845, as indicated. (B-H) The huMcl-1 and wild-type mice were treated with 5 consecutive doses of 12.5 mg/kg S63845 or vehicle. At 3 or 17 days posttreatment, organs were harvested for analysis. (B-F) Single-cell suspensions were prepared from spleen, thymus, and bone marrow of Mcl-1^hu/hu and Mcl-1^wt/wt mice and cell subsets were determined by immunostaining and FACS analysis. Data are presented as mean ± SEM, significance determined by the Student t test. *P < .05, **P < .01. (B) Representative FACS plot of B cells in the bone marrow and (C) total cell numbers per femur. B cells defined as pro-B/pre-B (B220^loIgM⁻), immature B (B220^loIgM^mid), transitional B (B220^lo-hiIgM^hi), and mature B cells (B220^hiIgM^mid). (D) Total numbers of B cells in the spleen (B220⁺) (E) LSK cells (Lineage⁻SCA-1⁺c-KIT⁺) and macrophages/monocytes (MAC-1⁺GR-1^lo) in the bone marrow (F) and mature T cells (CD4⁺ or CD8⁺) in the thymus at indicated time points. (G) Representative hematoxylin-and-eosin (H&E)-stained section of spleens from huMcl-1 or wild-type mice that had been treated with 12.5 mg/kg S63845 or vehicle and were harvested at either 3 or 17 days posttreatment. (H) Representative H&E-stained sections of various organs, as indicated, from huMcl-1 mice treated with 5 consecutive doses of 12.5 mg/kg S63845 or vehicle 3 days after treatment had ceased.