Protein and gene expression of BCR signaling components in persistent lymphocytes compared with baseline. Phosphorylated and total protein expression of various signaling molecules of the BCR pathway and gene expression of BTK and PLCγ2 were investigated in patients with persistent lymphocytosis. Serial samples were taken at baseline and at 6 or 9 months after initiation of therapy. Each immunoblot shown is representative of multiple patients evaluated, and statistics presented in the text show the mean change of all evaluated patients. Number of patients evaluated was determined by amount of sample available. (A) pBTK (Y223), as well as (C) pPLCγ2 (Y759) decrease in the majority of patients after ibrutinib therapy. (E) pERK (Thr202/Tyr204), (F) pMEK1/2 (Ser217/221), and (G) pAKT (Ser473) increase in the majority of patients with prolonged lymphocytosis during ibrutinib therapy. Gene expression of (B) BTK and (D) PLCγ2 does not change over time in the majority of patients.