Figure 2.
Genetically engineered mouse models of G3BP2-KIT leukemia. (A) Kaplan-Meier survival curves of C57BL6 mice receiving ARF-null pre-B cell transplants expressing G3BP2-KIT (after 14 days in culture without IL-7 [n = 4] or within 48 hours after transduction [n = 4]) or empty vector (MIG; n = 5) and of secondary recipients undergoing transplantation with cells from primary mouse tumors. Survival comparison was analyzed by log-rank test. (B) Spleen weight from primary and secondary recipient mice with G3BP2-KIT and from control mice (MIG). The mean weight is shown by the horizontal line in the scatter dot plot, and the error bars represent the standard deviations (SDs). (C) Dose-response curve of BaF3 cells expressing empty vector (MIG) or G3BP2-KIT fusion after 72 hours treatment with dasatinib, ponatinib, imatinib, nilotinib, sunitinib, or avapritinib. The cells transduced with the empty vector were grown in media with recombinant mouse IL-3. Values are normalized to dimethyl sulfoxide controls and represent means ± SDs from 3 independent experiments performed in triplicate. (D) Left panel shows levels (means + SDs) of GFP+ cells in the peripheral blood of C57BL6 mice receiving ARF-null pre-B leukemia cell transplants expressing G3BP2-KIT from 2 primary mouse tumor cohorts (a and b groups). In group a (n = 5), dasatinib (20 mg/kg daily) or vehicle (n = 5) was started 1 week after transplantation; in group b, treatment started 2 weeks after transplantation. Right panel shows Kaplan-Meier survival curves of mice in study treatment. IC50, 50% inhibitory concentration; ns, not significant.

Genetically engineered mouse models of G3BP2-KIT leukemia. (A) Kaplan-Meier survival curves of C57BL6 mice receiving ARF-null pre-B cell transplants expressing G3BP2-KIT (after 14 days in culture without IL-7 [n = 4] or within 48 hours after transduction [n = 4]) or empty vector (MIG; n = 5) and of secondary recipients undergoing transplantation with cells from primary mouse tumors. Survival comparison was analyzed by log-rank test. (B) Spleen weight from primary and secondary recipient mice with G3BP2-KIT and from control mice (MIG). The mean weight is shown by the horizontal line in the scatter dot plot, and the error bars represent the standard deviations (SDs). (C) Dose-response curve of BaF3 cells expressing empty vector (MIG) or G3BP2-KIT fusion after 72 hours treatment with dasatinib, ponatinib, imatinib, nilotinib, sunitinib, or avapritinib. The cells transduced with the empty vector were grown in media with recombinant mouse IL-3. Values are normalized to dimethyl sulfoxide controls and represent means ± SDs from 3 independent experiments performed in triplicate. (D) Left panel shows levels (means + SDs) of GFP+ cells in the peripheral blood of C57BL6 mice receiving ARF-null pre-B leukemia cell transplants expressing G3BP2-KIT from 2 primary mouse tumor cohorts (a and b groups). In group a (n = 5), dasatinib (20 mg/kg daily) or vehicle (n = 5) was started 1 week after transplantation; in group b, treatment started 2 weeks after transplantation. Right panel shows Kaplan-Meier survival curves of mice in study treatment. IC50, 50% inhibitory concentration; ns, not significant.

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