Figure 3.
Development of a clonal low-grade B-cell lymphoma and pre-B-ALL in engineered mice. (A) Kaplan-Meier survival plots illustrating overall survival of mouse cohorts according to genotype. P values were calculated by using the log-rank test. (B) Histologic and IHC stains of indicated markers in a representative example of low-grade B-cell lymphoma involving the lungs of a CD19Cre/+KrasG12D/+ mouse. Scale bar, 25 µm (see supplemental Figure 4). (C) Southern blot analysis for the immunoglobulin heavy chain (IgH) (left) and T-cell receptor (TCR) (right) genes in the same genomic DNA isolated from CD19Cre/+ LNs and CD19Cre/+KrasG12D/+ lymphomas. Clonal bands are present for the IgH gene (arrows) but not for TCR (see supplemental Figure 6D). (D) Representative gross pictures of enlarged LNs (white arrow) and spleen from CD19Cre/+Ink4a/ArfL/+ mouse with pre-B-ALL. Scale bar, 1 cm. (E) Histologic, IHC, and immunofluorescent stains of indicated markers in LNs and BM from representative CD19Cre/+Ink4a/ArfL/+ mouse with B-ALL. CD19 staining shown in green with blue 4′,6-diamidino-2-phenylindole (DAPI) nuclear counterstain. Note cytoplasmic expression of IgM in B-ALL cells. TBG, tingible body macrophage. Scale bars: white, 25 µm; black, 50 µm (see supplemental Figure 5). (F) Southern blot analysis for the IgH (left) and TCR (right) genes in the same genomic DNA isolated from CD19Cre/+Ink4a/ArfL/+ leukemias. Clonal bands are present for the IgH gene (arrows) but not for TCR. GL, germ line band.