PI3K-δ inhibitor GS-649443 is effective in mice transplanted with TCL1-192 cell line or primary TCL1 tumors. (A) Scheme for the 2 adoptive transfer models for studying the efficacy of GS-649443. Model 1 (green box) involves transfer of tumor from Eµ-TCL1 mice into syngeneic recipients, followed by 10 days of treatment with the inhibitor or vehicle. Model 2 (yellow box) involves transfer of TCL1-192 cells into 2 cohorts of immunodeficient recipients, with a cutoff after 5 days of treatment with vehicle or GS-649443 (cohort 2a) or survival as end point of the study (cohort 2b). (B) Representative photographs of spleens in the Eµ-TCL1 syngeneic tumor-transfer model after 10 days of treatment with GS-649443 or vehicle. Spleen weights (TCL1-192, P = .0053; syngeneic, P = .0033) (C), liver weights (TCL1-192, P = .0079; syngeneic, P = .0031) (D), and WBC counts (TCL1-192, P = .0078; syngeneic, P = .0047) (E) of recipient mice in the TCL1-192–transfer model (n = 6 mice per group), as well as in the syngeneic transfer model (n = 7 mice per group). Measurements were taken at the time of euthanization after 10 days (syngeneic) or 5 days (TCL1-192) of treatment. All P values were calculated using the Mann-Whitney U test. (F) Cell proliferation analyzed by BrdU injection 24 hours prior to euthanizing the mice (n = 6). The BrdU⁺ fraction of splenic lymphocytes in the immunosuppressed (TCL1-192, P = .0173) and immunocompetent (syngeneic, P = .0054) models is depicted. The P values were calculated using the Mann-Whitney U test. (G) Survival curves of NOD.SCID-Prkdc^scid recipient mice transferred with TCL1-192 tumor cells and treated with GS-649443 or vehicle (n = 6 mice per group). ***P ≤ .0001, log rank (Mantel-Cox) test. *P ≤ .05; **P ≤ .01; ***P ≤ .001; ns, P > .05.