Cd79b p.Y195H confers ibrutinib sensitivity in vivo. MBC, 79-MBC, PPMBC, and 79-PPMBC mice were monitored for lymphoma development by MRI and upon tumor diagnosis either left untreated or treated with ibrutinib. (A) MRI images illustrate a baseline scan and after 3 weeks of ibrutinib treatment for a representative animal of each genotype and cohort. (B) Volume changes of target lesions over time are visualized for all 4 genotypes. Progression-free survival (C) and OS (D) is illustrated . (E), (F) PLA detecting the proximity of MYD88 and CD79B was done on FFPE tissue sections of ibrutinib relapsed 79-MBC and 79-PPMBC lymphomas and compared with PLA counts of treatment-naïve lesions of the same genotype, as well as tumor samples isolated from acutely treated animals (30 mg/kg orally daily for 3 days). ∗P ≤ .05, ∗∗P ≤ .01, ∗∗∗P ≤ .001, ∗∗∗∗P ≤ .0001; (C-D) Log-rank test. (E-F) Welch 2-tailed t test, corrected for multihypothesis testing (Benjamini-Hochberg).