Disparity in gene expression between pretreatment samples collected at various times after diagnosis. (A) Histograms depicting the proportion of patients in the UC San Diego cohort who had sample collection (SC) at various years after diagnosis (DX), as indicated below the graph. The blue bar indicates the proportion of patients who had SC less than 1 year after DX. (B) Inverse histograms depicting the proportion of patients in the UC San Diego cohort who had SC at 1 or more years before therapy, as indicated in the scale above the graph. The samples are considered representative of patients with early-phase disease (“E”) if they were collected more than 4 years before therapy (green bars), intermediate phase (“I”) if collected 4 or less, but 1 or more, years before therapy (yellow bars), or late phase (“L”) if collected less than 1 year before therapy (red bars). The black bars in each colored bar depict the proportion of samples collected in that respective year before therapy that had CLL cells with mutated IGHV. (C) Gene expression differences between different phases of the disease (leftmost panel) and between IGHV subgroups at different phases (middle panel). Bars chart the mean number of differentially expressed genes from 5 trials of 2-tail t tests on 12 versus 12 samples with P value cutoffs at .05. Permutation tests on the same sample sets were performed to assess the numbers of false positives (rightmost panel). (D) Treatment-free survival analyses of all 130 UC San Diego patients using published marker sets. Bars chart the P value of the difference between the low- and high-risk groups, defined by each marker set reported previously. Each marker set is evaluated on both DX→TX (blue bars) and SC→TX (red bars). Bars with * or # denote P value of the difference between SC→TX for samples segregated via IGHV mutation status when the time from DX→SC was less than 1 year (*) or more than year (#), respectively.