Study on activation of AKT/mTOR pathway in anaplastic large cell lymphoma.
- Author:
Jin-Fan LI
1
;
Gan-di LI
;
Ling GU
;
Wei-Ping LIU
;
Feng-Yuan LI
;
Dian-Ying LIAO
;
Zhi-Gui MA
Author Information
- Publication Type:Journal Article
- MeSH: Adaptor Proteins, Signal Transducing; metabolism; Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Intracellular Signaling Peptides and Proteins; metabolism; Lymphoma, Large-Cell, Anaplastic; metabolism; Male; Middle Aged; Phosphoproteins; metabolism; Phosphorylation; Protein-Serine-Threonine Kinases; metabolism; Protein-Tyrosine Kinases; metabolism; Proto-Oncogene Proteins c-akt; metabolism; Receptor Protein-Tyrosine Kinases; Ribosomal Protein S6 Kinases, 70-kDa; metabolism; Signal Transduction; TOR Serine-Threonine Kinases; Young Adult
- From: Chinese Journal of Hematology 2008;29(10):649-653
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the expression of anaplastic lymphoma kinase (ALK) and the phosphorylation status of AKT, mammalian target of rapamycin (mTOR), 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (p70S6K) and their interrelationships and clinical pathological significance in anaplastic large cell lymphoma (ALCL) patients.
METHODSImmunohistochemical and EnVision methods were used to detect the expression of ALK, p-AKT, p-mTOR, p-4E-BP1 and p-p70S6K.
RESULTSAmong the 81 ALCL patients, 51 (63.0%) expressed ALK, whereas the other 30 (37.0%) did not. Patients with ALK(+) ALCL had a better prognosis than those with ALK-ALCL (P < 0.05). Out of the 71 ALCL samples studied, p-AKT was detected in 54 (76.1%) samples and its phosphorylation was correlated with ALK expression (P < 0.05); p-mTOR was detected in 57 (80.3%) samples and its expression was correlated with both ALK and p-AKT (P < 0.05); p-4E-BP1 and p-p70S6K were detected in 64 (90.1%) and 66 (93.0%) samples respectively, and their expressions were related with p-mTOR (P < 0.05), but not with ALK or p-AKT (P > 0.05). COX Proportional Hazard Model analysis showed that both the expression of ALK and the B symptoms affected the prognosis (P < 0.05), moreover, the former had greater impact than the later.
CONCLUSIONExpressions of p-AKT, p-mTOR, p-4E-BP1 and p-p70S6K are detected in ALCL, while ALK(+) cases have higher incidence than those with ALK(-) cases. Phosphorylation of AKT and mTOR is correlated with ALK expression, suggesting that there is an activated pathway of AKT/mTOR in patients with ALK(+) ALCL, but the activation have no obvious prognostic significance.