case_images: PMC7027364_01
case_images: Phosphorylation patterns in the PI3K pathway in peripheral blood T-lymphocytes before (A) and after (B) therapy in case 1. Case 2 patient had a germline variant of PIK3CD, which was present in the tumor as well. Peripheral blood T-lymphocytes (patient 1's lymphocytes contained only T cells at the time of testing) were tested for activation of the PI3K signaling pathway [reflected as a phosphorylation of Akt (Ser473), mTOR (Ser2448), and S6 ribosomal protein (Ser235/236)] before and following therapy. (A) Patient T-lymphocytes showed increased basal phosphorylation of Akt as well as increased phosphorylation of Akt and S6 upon T-cell receptor (TCR) stimulation before treatment compared to an independent healthy control (the result is representative of three independent tests). (B) A week following the addition of idelalisib (a PI3K inhibitor), to the patient's therapy, the phosphorylation of Akt, mTOR, and S6 dropped down. CD3+ T-lymphocytes are shown in basal state (tinted histograms) and 15 min upon anti-CD3/CD28/CD49d stimulation (blank histograms). Red, patient 1; black, healthy control.
case_images: fonc-09-01531-g0001.jpg
case_images: PMC7027364_01_fonc-09-01531-g0001.jpg
case_images: F1
case_images: T-lymphocytes and detected increased basal and T-cell receptor (TCR)-induced activation (Figure 1A). Similarly, increased levels of PI3K were confirmed by RNA transcriptome analysis of the tumor tissue with Affymetrix GeneChipST 1.0. This analysis also revealed an increased expression of HR23B, a predictor of response to histone deacetylase (HDAC) inhibitors. T-lymphocytes (Figure 1B), but the disease was still showing further radiological progression. Therapy with idelalisib was not discontinued, and ibrutinib 140 mg/m2 daily was reintroduced.
case_images: PMC7027364_02
case_images: PMC7027364_03