Jung Yong Hong1, Min Eui Hong2, Moon Ki Choi3, Wonjin Chang4, In-Gu Do5, Ji-Suk Jo5, Sin-Ho Jung6, Silvia Park7, Seok Jin Kim7, Young Hyeh Ko2, Won Seog Kim8. 1. Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea. 2. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 3. Divisions of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi-do, Republic of Korea. 4. Division of Hematology-Oncology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea. 5. Samsung Cancer Research Institute, Samsung Medical Center, Seoul, Republic of Korea. 6. Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, U.S.A. 7. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 8. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea wskimsmc@skku.edu.
Abstract
BACKGROUND: The oncogenic PI3K/serine-threonine kinase (PI3K/AKT) pathway is a downstream pathway of B-cell receptor (BCR) signaling pathway and plays a crucial role in the pathogenesis of B-cell lymphoma. However, there have been preclinical data showing PI3K/AKT pathway activation in T-cell lymphoma, with in different mechanisms from those in B-cell lymphoma. In this study, we investigated the impact of p-AKT expression on clinical outcomes of peripheral T-cell lymphoma (PTCL). MATERIALS AND METHODS: We analyzed 63 patients with PTCL [PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL) or extranodal natural kiler T-cell lymphoma (NKTCL)]. To define the clinical implications of p-AKT expression in PTCL, we calculated arbitrary units (AUs) by multiplying the intensity and the proportion of p-AKT expression. RESULTS: Based on a cutoff value of the upper limit of the third quartile (Q3) of the AU, 12 patients were classified into the high p-AKT group, while the remaining 51 patients were classified into the low p-AKT group. The overall response rate to frontline chemotherapy was significantly lower in the high p-AKT group than in the low p-AKT group (20.0% vs. 71.1%, p=0.004). The high p-AKT group showed substantially worse overall survival (OS) (median OS=2.3 vs. 25.2 months, p<0.001) and progression-free survival (PFS) (median PFS=1.6 vs. 8.8 months, p<0.001) compared with the low p-AKT group. Multivariate analysis showed that high p-AKT expression remained a significant independent poor prognostic factor for OS (hazard ratio (HR)=7.0; 95% confidence interval (CI)=3.0-16.6; p<0.001) and PFS (HR=6.8; 95% CI=3.0-15.2; p<0.001). CONCLUSION: PTCL patients with high p-AKT expression showed aggressive clinical courses with significantly worse OS and PFS and a poor chemotherapy response rate. We suggest that targeting the PI3K/AKT pathway may be a promising therapeutic strategy for PTCL. Copyright
BACKGROUND: The oncogenic PI3K/serine-threonine kinase (PI3K/AKT) pathway is a downstream pathway of B-cell receptor (BCR) signaling pathway and plays a crucial role in the pathogenesis of B-cell lymphoma. However, there have been preclinical data showing PI3K/AKT pathway activation in T-cell lymphoma, with in different mechanisms from those in B-cell lymphoma. In this study, we investigated the impact of p-AKT expression on clinical outcomes of peripheral T-cell lymphoma (PTCL). MATERIALS AND METHODS: We analyzed 63 patients with PTCL [PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL) or extranodal natural kiler T-cell lymphoma (NKTCL)]. To define the clinical implications of p-AKT expression in PTCL, we calculated arbitrary units (AUs) by multiplying the intensity and the proportion of p-AKT expression. RESULTS: Based on a cutoff value of the upper limit of the third quartile (Q3) of the AU, 12 patients were classified into the high p-AKT group, while the remaining 51 patients were classified into the low p-AKT group. The overall response rate to frontline chemotherapy was significantly lower in the high p-AKT group than in the low p-AKT group (20.0% vs. 71.1%, p=0.004). The high p-AKT group showed substantially worse overall survival (OS) (median OS=2.3 vs. 25.2 months, p<0.001) and progression-free survival (PFS) (median PFS=1.6 vs. 8.8 months, p<0.001) compared with the low p-AKT group. Multivariate analysis showed that high p-AKT expression remained a significant independent poor prognostic factor for OS (hazard ratio (HR)=7.0; 95% confidence interval (CI)=3.0-16.6; p<0.001) and PFS (HR=6.8; 95% CI=3.0-15.2; p<0.001). CONCLUSION: PTCL patients with high p-AKT expression showed aggressive clinical courses with significantly worse OS and PFS and a poor chemotherapy response rate. We suggest that targeting the PI3K/AKT pathway may be a promising therapeutic strategy for PTCL. Copyright
Authors: Ajay Major; Justin Kline; Theodore G Karrison; Paul A S Fishkin; Amy S Kimball; Adam M Petrich; Sreenivasa Nattam; Krishna Rao; Bethany G Sleckman; Kenneth Cohen; Koen van Besien; Aaron P Rapoport; Sonali M Smith Journal: Haematologica Date: 2022-07-01 Impact factor: 11.047