Figure 3.
Association of redox sensitivity with biological and clinical characteristics and clinical progression. (A) Responses of BCR signaling proteins, measured as the log2-fold change in phosphorylation between H2O2-modulated and unmodulated conditions, were associated with biological and clinical parameters (ie, IGHV status [n = 42], CD38 expression [n = 42], ZAP70 expression [n = 42], cytogenetic mutations [n = 41], Binet stage [n = 42], and requirement of treatment during follow-up [n = 42]). Differences in sample sizes depend on availability of biological and clinical information. Lines indicate mean values. Student t test and 1-way ANOVA test were used for comparisons, as appropriate. *P ≤ .05; **P ≤ .01. (B) Kaplan-Meier curves of TTFT for subgroups of patients with CLL defined by pSYK (n = 41), pERK1/2 (n = 41), or the sum of pSYK, pERK1/2, and pp38 (n = 41) responses to H2O2 (each measured as log2-fold change). High and low pSYK and pERK1/2 values (log2-fold change) were defined using threshold values of the probability density function of log2-fold phosphoprotein data (see supplemental Methods and supplemental Figure 4). P values are from the logrank test. High and low summing value was defined using the median value of the distribution. The dot plot shows pSYK, pERK1/2, and pp38 responses to H2O2 for each individual patient, as described in Figure 1C. High and low values used to compute the Kaplan-Meier curves are highlighted in red and blue, respectively. Lines indicate median values.