We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Evaluation of the PIK3 pathway in peripheral T‐cell lymphoma and NK/T‐cell lymphoma.
- Authors
Huang, Dachuan; Song, Tammy Linlin; Nairismägi, Maarja‐Liisa; Laurensia, Yurike; Pang, Wan‐Lu; Zhe, Daryl Cheah Ming; Wong, Esther Kam Yin; Wijaya, Giovani Giovani‐Clarest; Tan, Jing; Tan, Sze Huey; Lim, Jing‐Quan; Chia, Burton Kuan Hui; Chan, Jason Yongsheng; Tang, Tiffany Pooi Ling; Somasundaram, Nagavalli; Cheng, Chee Leong; Politz, Oliver; Liu, Ningshu; Lim, Soon Thye; Ong, Choon Kiat
- Abstract
Summary: Peripheral T‐cell lymphomas (PTCL) and natural killer (NK)/T‐cell lymphomas (NKTCL) are a heterogeneous group of aggressive malignancies with dismal outcomes and limited treatment options. While the phosphatidylinositol 3‐kinase (PIK3) pathway has been shown to be highly activated in many B‐cell lymphomas, its therapeutic relevance in PTCL and NKTCL remains unclear. The aim of this study is to investigate the expression of PIK3 and phosphatase and tensin homolog (PTEN) in these subtypes of lymphoma and to identify potential therapeutic targets for clinical testing. Therefore, the expression of PIK3α, PIK3β, PIK3γ, PIK3δ and PTEN was analyzed in 88 cases of PTCL and NKTCL samples by immunohistochemistry. All PTCL and NKTCL samples demonstrated high expression of PIK3 isoforms. In particular, high PIK3α expression was significantly associated with poor survival, even after adjustment for age, International Prognostic Index (IPI) score and anthracycline‐based chemotherapy in first line. Notably, copanlisib, a pan‐class I inhibitor with predominant activities towards PIK3α and PIK3δ isoforms, effectively inhibited phosphorylation of AKT, 4E‐BP‐1 and STAT3, causing G0/G1 cell cycle arrest and resulting in suppression of tumour cell growth in vitro and in vivo. This study provides evidence that targeting the PIK3 pathway, particularly simultaneous inhibition of PIK3α and δ, could be a promising approach for the treatment of PTCL and NKTCL.
- Subjects
T-cell lymphoma; PTEN protein; CELL growth; CELL cycle; LYMPHOMAS; CUTANEOUS T-cell lymphoma; EXTRANODAL NK-T-cell lymphoma; PHOSPHATIDYLINOSITOL 3-kinases
- Publication
British Journal of Haematology, 2020, Vol 189, Issue 4, p731
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/bjh.16435