Role of CXCR4^WHIM mutations in MYD88^L265P-mutated WM. (A) PCA of the top 500 high variance genes within the WM patient samples using the first 2 principal components. WM patients with the MYD88^L265PCXCR4^WT genotype are shown in red; patients mutated for MYD88 with CXCR4 nonsense (NS) or frameshift (FS) mutations are shown in dark and light green, respectively; and patients with MYD88^WTCXCR4^WT are shown in purple. (B) Heat map of the 3103 genes differentially expressed between the MYD88^L265PCXCR4^WT and MYD88^L265PCXCR4^WHIM genotyped samples. Gene order was determined using hierarchical clustering of MYD88^L265PCXCR4^WT and MYD88^L265PCXCR4^WHIM expression data whereas the samples where arranged by genotype. Expression data for MYD88^WTCXCR4^WT WM and healthy donor B-cell samples were added to the heat map for comparison with intact clustered gene order. (C) Top predicted upstream targets of the differentially expressed genes from Ingenuity Pathway Analysis.