Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of aggressive malignancies with dismal outcomes and limited treatment options. While the PI3K pathway has been shown to be activated in many B-cell lymphomas, its therapeutic relevance in PTCL is not clear. The aim of this study was to investigate the expression and activation of the signaling molecules in the PI3K pathway in each subtype of PTCL and to identify the potential therapeutic options for clinical testing.
The expression of PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ, AKT1, pAKT1 and PTEN was analyzed in 88 PTCL samples by immunohistochemistry. This included all major mature T- and NK-cell neoplasms. Uni- and multivariate analyses were also performed using the expression and patients’ clinical data.
Staining for PI3Kα and AKT1 was positive in 86 (98%), PI3Kδ in 85 (97%), PI3Kβ in 79 (90%), PI3Kγ in 50 (57%) and pAKT1 in 45 (51%) samples. No PTEN staining was observed in 9 (10%) cases and the expression was weak in 70 (80%) samples. There were no correlations between expression and PTCL subtype. Patients with positive pAKT1 had higher IPI score (P = 0.004) and higher stage (P = 0.02). Loss and low expression of PTEN were associated with older age at diagnosis (P = 0.02). In the univariate analysis, high PI3Kα, older age, high IPI and high ECOG score were significantly associated with inferior OS and PFS (P
All 88 samples demonstrated at least partial activation of the PI3K pathway. High PI3Kα expression was an independent poor prognostic factor for both OS and PFS. This study provides evidence that targeting the PI3K pathway, particularly inhibition of PI3Kα, could be a promising approach for the treatment of PTCL.
Clinical trial identification
Legal entity responsible for the study
Choon Kiat Ong
O. Politz, N. Liu: Employee of Bayer AG. C.K. Ong: Received research funding from Bayer AG. All other authors have declared no conflicts of interest.