The tissue microenvironment affects the tumor biology of CLL cells in vivo. (A) Gene expression analysis of fresh CLL tumor cells derived from PB, BM, and LN in treatment-naive patients in whom all 3 sites were evaluable (n = 12). Principal component analysis of gene expression normalized for patient effect (see “Microarray hybridization, data processing, and analysis”) is shown. (B) Heat map of 151 genes differentially expressed in purified CLL cells obtained simultaneously from LN and PB in 17 patients (> 2-fold change, FDR < 20%). Patient samples are arranged in columns keeping the same order in the LN and PB groups. Gene expression is median-centered and scaled as indicated. Gene symbols highlight select genes. (C) Heat map of 26 differentially expressed genes in purified CLL cells isolated from BM aspirates compared with cells simultaneously obtained from the PB in 19 patients (> 2-fold change, FDR < 20%).