[Study on activation of AKT/mTOR pathway in anaplastic large cell lymphoma]

Zhonghua Xue Ye Xue Za Zhi. 2008 Oct;29(10):649-53.
[Article in Chinese]

Abstract

Objective: To 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.

Methods: Immunohistochemical and EnVision methods were used to detect the expression of ALK, p-AKT, p-mTOR, p-4E-BP1 and p-p70S6K.

Results: Among 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.

Conclusion: Expressions 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adolescent
  • Adult
  • Aged
  • Anaplastic Lymphoma Kinase
  • Cell Cycle Proteins
  • 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

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • MTOR protein, human
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases