CD22ΔE12 signature transcriptome in human and mouse BPL cells.
Depicted are GSE plots comparing the human vs. mouse CD22ΔE12 signature transcriptomes in BPL cells. Rank-ordered correlation coefficients (y-axis expression of each probeset plotted against CD22 Exon 12 Index on the x-axis) were processed for enrichment of the signaling pathway-linked gene sets obtained from the Reactome Database (c2.cp.reactome.v4.0.symbols deposited in database on broadinstitute.org servers) using a supervised approach implemented in GSEA2.08 (Broad Institute). Probesets for (i) “MAPK targets/nuclear events mediated by MAP kinases” pathway (panel A), (ii) MAPK pathway (panel B), (iii) PI3-K/mTOR activation pathway (panel C), and (iv) WNT pathway (panel D) negatively correlated with Exon 12 transcript levels in human BPL samples from high-risk ALL patients indicating that the transcripts were differentially upregulated upon loss of CD22 Exon 12 (enrichment observed towards the negative correlation co-efficient values). The mouse homologs of these genes were also upregulated in murine BPL cells derived from CD22ΔE12-Tg mice (enrichment observed towards negative T-values depicting genes downregulated in WT/BCR-ABL/Eμ-MYC Tg mice). Nominal P-values for GSEA enrichment scores for expression change in mouse and human transcriptomes were combined using Fisher's method to determine the significance of the representation of the pathway in both human and mouse cells (combined P-value).