Lower ATM levels are associated with reduced overall survival in a cohort of patients. (A) Kaplan Meier curves constructed using a cohort of patients (supplemental Table 3) (n = 57). (i) Overall survival of the whole cohort. Median survival 124 months. (ii) Overall survival by immunoglobulin heavy chain gene mutational status (solid red line mutated and dotted blue line unmutated). Median survival of mutated patients 168 months and unmutated 75.5 months. Log-rank test P ≤ .0001. (iii) Overall survival by sex (solid red line, female; dotted blue line, male). Median survival of female patients 168 months and males 117 months. Log-rank test P = .402. (iv) Overall survival by Binet stage (solid red line stage A and dotted blue line stages B and C). Median survival of stage A patients 165.5 months and stages B and C 92.3 months. Log-rank test P = .0037. (B) Overall survival of the entire cohort, including patients with 11q deletion, by ATM level (solid red line patients with ATM levels above the median and dotted blue line patients with ATM levels below the median). Median survival of patients with ATM greater than median (n = 28) 178.5 months and patients less than median (n = 29) 99.5 months. Log-rank test P = .023. (C) Overall survival of 11q deleted patients (n = 11) (dashed green line), patients with ATM levels less than median and intact 11q (n = 21) (dotted blue line) and patients with ATM levels greater than median and intact 11q (n = 25) (solid red line). Median survival of 11q deleted patients 79 months, patients with ATM levels less than median 117 months and patients with ATM levels greater than median 178.5 months. There is a significant difference in survival between patients with ATM levels greater than median and 11q deleted patients (log-rank test P = .044) but not for the other comparisons. (D) Overall survival of patients (excluding 11q deleted cases) with ATM levels in the lower tercile (n = 18) (dotted blue line) and patients with ATM levels in the upper tercile (n = 18) (solid red line). Median survival of lower tercile patients 110.8 months and patients with ATM levels in the upper tercile 290 months. There is a significant difference in survival (log-rank test, P = .0037). (E) Summary. CD40L/IL-4 stimulation promotes global translation and translational regulation of the ATM pathway to different degrees in different individuals. CD40L/IL-4 responses are correlated with survival and DNA repair following XR and CD40L/IL-4 drives ATM steady-state protein levels and levels of ATM target proteins, ph-p53, and γH2AX.