Fig. 5

Atm-deficient CLLs display an actionable dependence on PARP. ATM has been shown to regulate HR-mediated DNA DSB repair. To directly address a potential dependence of Atm-deficient CLLs on the PARP-dependent BER pathway, we treated leukemic TC and TCA animals with the PARP inhibitor olaparib (50 mg/kg, i.p., daily, 5 days/week) and monitored disease progression and overall survival. Control cohorts were left untreated. The CD5⁺/CD19⁺ fractions of peripheral blood lymphocytes of olaparib-treated or untreated TCA and TC animals are illustrated in a. Numbers above bars indicate the number of mice that were alive at the time of imaging in each group. Lymphadenopathy was monitored through MR imaging in 8 week intervals. Representative images of mice scanned at day 0 and day 112 of treatment/observation are shown in b. The fold change of spleen volumes of olaparib-treated and untreated mice is illustrated in c. d Overall survival of TC and TCA mice treated with olaparib or left untreated. Error bars represent standard deviation. b, c Welch’s t-test, d log-rank test. *p < 0.05, **p < 0.01