title: The clinical significance of activated p-AKT expression in peripheral T-cell lymphoma.
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).
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors: Jung Yong
authors: JY
authors: Hong
authors: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Min Eui
authors: ME
authors: Hong
authors: 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.
authors: Moon Ki
authors: MK
authors: Choi
authors: Division of Hematology-Oncology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors: Wonjin
authors: W
authors: Chang
authors: Samsung Cancer Research Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors: In-Gu
authors: IG
authors: Do
authors: Samsung Cancer Research Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors: Ji-Suk
authors: JS
authors: Jo
authors: Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, U.S.A.
authors: Sin-Ho
authors: SH
authors: Jung
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Silvia
authors: S
authors: Park
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Seok Jin
authors: SJ
authors: Kim
authors: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Young Hyeh
authors: YH
authors: Ko
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea wskimsmc@skku.edu.
authors: Won Seog
authors: WS
authors: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics* / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051058:Oncogene Protein v-akt / Q000096:biosynthesis* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D015398:Signal Transduction
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt
keywords: PI3K/AKT pathway; p-AKT; peripheral T-cell lymphoma