Fig. 5

Splenic B^VETrp53^KO or B^VEpTEN^KO leukemic cells have unique gene expression signatures. A The lineage-specific gene expression signatures in HSC^VE, B^VEP53^−/− or B^VEPTEN^−/− leukemic cells were explored by RNA-seq analysis. RNA samples (three samples per group) were extracted from purified splenic B cells and were analyzed by next-generation sequencing. The hierarchical clustering heatmap was generated as described in Materials and Methods. Signature #1, gene clusters down-regulated in all three leukemic cells; Signature #2, gene clusters up-regulated in HSC^VE and B^VEP53^−/− leukemic cells; Signature #3 gene clusters up-regulated in B^VEP53^−/− and B^VEPTEN^−/− leukemic cells; Signature #4, #5, and #6, lineage-specific gene clusters up-regulated in HSC^VE, B^VEP53^−/− or B^VEPTEN^−/− leukemic cells. B A Venn diagram of genes that were up-regulated (upper panel) or down-regulated (lower panel) in HSC^VE, B^VEP53^−/− and B^VEPTEN^−/− leukemic cells. C-I Differential cellular programs were turned on in HSC^VE, B^VEP53^−/− and B^VEPTEN^−/− leukemic cells. Ingenuity pathway analyses (IPA) of prominent gene signatures of HSC^VE, B^VEP53^−/− or B^VEPTEN^−/− leukemic cells shown in the hierarchical heatmap (A) or the Venn diagrams (B) was calculated as described in the Materials and Methods, and then the pathways that regulate approximate cellular function were categorized accordingly. C-D, Cellular activities were enhanced (C) or dampened (D) in all three leukemic cells. E-F, Cellular activities were up-regulated in HSC^VE and B^VEP53^−/− leukemic cells (E) or B^VEP53^−/− and B^VEPTEN^−/− leukemic cells (F). G-I, Cellular activities were elevated in HSC^VE leukemic cells (G), or B^VEP53^−/− leukemic cells (H), or B^VEPTEN^−/− leukemic cells (I). In all experiments, splenic B cells were isolated from mice with terminal stage disease or mice without disease at 28 weeks. All data are representative of three mice per group