Tumor proliferation and c-MYC activation in the tissue microenvironment. (A) Genes of the E2F and c-MYC signatures that were most significantly enriched in the LN as identified by GSEA (leading-edge genes) are depicted in a heat map for the 12 patients having contributed cells from all 3 compartments. For E2F only genes that were at least 1.5-fold more highly expressed in LN than PB are shown. (B) The E2F and c-MYC scores were computed individually as the average of the mRNA expression level of the leading-edge genes for each sample. Shown is the ratio of the E2F and c-MYC scores in BM (n = 19) or LN (n = 17) relative to the score of the matched PB sample. Comparison between BM and LN was by Student t test. (C) Western blot of nuclear protein extracts from purified CLL cells were probed with anti-E2F1 or anti–c-MYC antibody, quantified by densitometry, and normalized to TBP. The ratios of LN- to PB-derived cells for E2F1 and c-MYC protein expression are indicated.