Differentially expressed genes between CLL fractions show unique features associated with cell survival and patient outcome. (A) Venn diagrams showing overlaps between our set of DEGs in RF vs PF cells and those previously described.⁶  Those overlaps were significantly enriched as measured by Fisher's exact tests (combined DEGs: P < 5e-320, odds ratio [OR] = 61.9; DEGs up in PF: P < 2e-268, OR = 90.1; DEGs up in RF: P = 1e-112, OR = 64.8). (B) Comparative expression of the 2 genes CXCR4 and CD5 that inversely change their levels and were used for FACS sorting of PF and RF. CXCR4 was significantly upregulated in RF (P < 5e-8 in U-CLL and P < 3e-6 in M-CLL), while CD5 was significantly more expressed in PF (P < 9e-6 in U-CLL and P < 5e-7 in M-CLL). (C) Venn diagram showing overlaps of intraclonal DEGs that associate with TTFT uniquely in either PF or RF as identified by Cox proportional hazards model or by log-rank test after stratifying patients according to gene expression levels. (D) Scatter plots of log₂ fold-change vs log₁₀P values in differential expression analysis from PF to RF (dots represent Illumina probes). Only DEGs associated with TTFT in PF (top) or RF (bottom) and overlapping in panel C are shown. (E) Comparative expression of representative intraclonal DEGs associated with TTFT and either upregulated in PF (CCND2, ILMN_2067656) or upregulated in RF (TJAP1, ILMN_1743763). (F) Kaplan-Meier curves of TTFT for CLL patients stratified according to an optimal cutoff for CCND2 (ILMN_2067656) or TJAP1 (ILMN_1743763) expression levels. P values were determined using the log-rank test. TTFT is in months.*P < .05, **P < .01, ***P < .001.