SETD1B is a tumor suppressor for B cell lymphoma. (A) Tumor latencies in animals receiving VavP-Bcl2/Cas9 transgenic HPCs transduced with sgRNA targeting LacZ (sgLacZ, black, n = 22) or sgRNA targeting Setd1b and/or Kmt2d (sgSetd1b, green, n = 19; P = 0.011; sgKmt2d, blue n = 8, P = 0.026; sgKmt2d+sgSetd1b, red, n = 10, P < 0.0001). P values were calculated using the Log-rank (Mantel–Cox) test. *P < 0.05, ****P < 0.0001. (B) Bar graphs showing the spleen/body weight ratio of recipient mice carrying sgLacZ (n = 22) or sgSetd1b (n = 27, pooled from sg1 and sg2, P < 0.0001), sgKmt2d (n = 8, P < 0.008), and sgSetd1B+sgKmt2d (n = 6, P < 0.0009). P values were calculated by two-way ANOVA followed by Tukey’s multiple comparisons test. **P < 0.01, ***P < 0.001, ****P < 0.0001. (C) Representative immunohistochemistry serial micrographs of VavP-Bcl2 spleen tissues extracted from recipient mice upon sacrifice VavP-Bcl2;sgLacZ, VavP-Bcl2;sgSetd1b, VavP-Bcl2;sgKmt2d, and VavP-Bcl2; sgSetd1b+Kmt2d were stained with H&E, B220, Ki67, PNA, TUNEL, and BCL6 (n = 3). Scale bar, 200, 500 μm. (D) Tumor volume growth curve of xenografted OCI-LY19;sgSETD1B and OCI-LY19;sgLacZ. P values were calculated by Student’s t test. ****P < 0.0001; n = 5. (E) Graph showing tumor weight comparison of OCI-LY19; sgSETD1B and OCI-LY19; sgLacZ. P values were calculated by Student’s t test. ***P = 0.0022; n = 5.