Figure 2.
TFAP4 is a c-MYC–induced cell-intrinsic tumor suppressor in developing B cells. (A) Survival analysis of Eμ-Myc mice crossed to Tfap4+/+ mice (n = 68), Tfap4+/− mice (n = 50), or Tfap4−/− mice (n = 6). The median survival was 134, 62, and 36 days, respectively. (B) Frequencies of surface Ig−Rag1+ VpreB1+ (immature) and Ig+Rag1− VpreB1− (mature) B-cell tumors in Eμ-Myc mice with distinct Tfap4 genotypes (Eμ-Myc Tfap4+/+, n = 10; Eμ-Myc Tfap4+/−, n = 14; Eμ-Myc Tfap4−/−, n = 2). (C) Survival of Eμ-Myc mice with Cd79aicre–mediated deletion of the Tfap4 allele in developing B cells (Tfap4F/+ or Tfap4F/F cre− [n = 59], median survival, 104 days; Tfap4+/+ Cd79aicre/+ [n = 16], median survival, 113 days; Tfap4F/+ Cd79aicre/+ [n = 17], median survival, 59 days; Tfap4F/F Cd79aicre/+ [n = 6], median survival, 42 days). (D) Tumorigenesis of Tfap4+/+ or Tfap4−/− BM CD19+ cells retrovirally transduced with mouse c-MYC (T58A) and adoptively transferred into sublethally irradiated CD45.1 mice (Tfap4+/+ [n = 10], median survival, undefined days; Tfap4−/− [n = 12], median survival, 83.5 days;). Two independent experiments were combined. (E) Survival of mice receiving Tfap4+/+ or Tfap4−/− BM CD19+ cells transduced with human P190 bcr-abl–expressing retrovirus and adoptively transferred into sublethally irradiated CD45.1 mice (Tfap4+/+ [n = 9], median survival, 32 days; Tfap4−/− [n = 10], median survival, 19.5 days). Two independent experiments were combined. (F) Survival of lethally irradiated CD45.1 mice reconstituted with BM cells from Cγ1-cre R26StopLSL-MYC × R26StopLSL-P110* mice of the indicated Tfap4 genotypes following immunization with sheep red blood cells. Data are combined from 4 independent experiments. Tfap4+/+ (n = 12), median survival, 88 days; Tfap4F/+ (n = 14), median survival, 74.5 days; Tfap4F/F (n = 15), median survival: 27 days. **P < .01, ***P < .001, log-rank test adjusted for multiple comparisons. RV, retrovirus.

TFAP4 is a c-MYC–induced cell-intrinsic tumor suppressor in developing B cells. (A) Survival analysis of Eμ-Myc mice crossed to Tfap4+/+ mice (n = 68), Tfap4+/− mice (n = 50), or Tfap4−/− mice (n = 6). The median survival was 134, 62, and 36 days, respectively. (B) Frequencies of surface Ig−Rag1+ VpreB1+ (immature) and Ig+Rag1− VpreB1− (mature) B-cell tumors in Eμ-Myc mice with distinct Tfap4 genotypes (Eμ-Myc Tfap4+/+, n = 10; Eμ-Myc Tfap4+/−, n = 14; Eμ-Myc Tfap4−/−, n = 2). (C) Survival of Eμ-Myc mice with Cd79aicre–mediated deletion of the Tfap4 allele in developing B cells (Tfap4F/+ or Tfap4F/F cre− [n = 59], median survival, 104 days; Tfap4+/+ Cd79aicre/+ [n = 16], median survival, 113 days; Tfap4F/+ Cd79aicre/+ [n = 17], median survival, 59 days; Tfap4F/F Cd79aicre/+ [n = 6], median survival, 42 days). (D) Tumorigenesis of Tfap4+/+ or Tfap4−/− BM CD19+ cells retrovirally transduced with mouse c-MYC (T58A) and adoptively transferred into sublethally irradiated CD45.1 mice (Tfap4+/+ [n = 10], median survival, undefined days; Tfap4−/− [n = 12], median survival, 83.5 days;). Two independent experiments were combined. (E) Survival of mice receiving Tfap4+/+ or Tfap4−/− BM CD19+ cells transduced with human P190 bcr-abl–expressing retrovirus and adoptively transferred into sublethally irradiated CD45.1 mice (Tfap4+/+ [n = 9], median survival, 32 days; Tfap4−/− [n = 10], median survival, 19.5 days). Two independent experiments were combined. (F) Survival of lethally irradiated CD45.1 mice reconstituted with BM cells from Cγ1-cre R26StopLSL-MYC × R26StopLSL-P110* mice of the indicated Tfap4 genotypes following immunization with sheep red blood cells. Data are combined from 4 independent experiments. Tfap4+/+ (n = 12), median survival, 88 days; Tfap4F/+ (n = 14), median survival, 74.5 days; Tfap4F/F (n = 15), median survival: 27 days. **P < .01, ***P < .001, log-rank test adjusted for multiple comparisons. RV, retrovirus.

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