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

Jin-Fan Li1, Gan-di Li, Ling Gu

  • 1Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China.

Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi
|January 30, 2009
PubMed
Abstract

Insights

Anaplastic Lymphoma Kinase (ALK) expression is common in Anaplastic Large Cell Lymphoma (ALCL) and linked to a better prognosis. The AKT/mTOR pathway is activated in ALK-positive ALCL, but its direct impact on prognosis is not significant.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pathology

Background:

  • Anaplastic Large Cell Lymphoma (ALCL) is a distinct subtype of non-Hodgkin lymphoma.
  • The role of Anaplastic Lymphoma Kinase (ALK) and the AKT/mTOR signaling pathway in ALCL pathogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the expression of ALK and the phosphorylation status of key proteins in the AKT/mTOR pathway (AKT, mTOR, 4E-BP1, p70S6K) in ALCL.
  • To determine the interrelationships between these markers and their clinical-pathological significance, particularly concerning patient prognosis.

Main Methods:

  • Immunohistochemistry and EnVision techniques were employed to detect the expression of ALK, phosphorylated AKT (p-AKT), phosphorylated mTOR (p-mTOR), phosphorylated 4E-BP1 (p-4E-BP1), and phosphorylated p70S6K (p-p70S6K).
  • Statistical analyses, including COX Proportional Hazard Model, were used to assess correlations and prognostic impact.

Main Results:

  • ALK expression was observed in 63.0% of 81 ALCL patients, with ALK-positive (ALK(+)) ALCL showing a better prognosis (P < 0.05).
  • Phosphorylation of AKT and mTOR was significantly correlated with ALK expression (P < 0.05), indicating an activated AKT/mTOR pathway in ALK(+) ALCL.
  • While p-4E-BP1 and p-p70S6K expressions correlated with p-mTOR (P < 0.05), they did not show a significant relationship with ALK or p-AKT status. ALK expression and B symptoms were significant prognostic factors.

Conclusions:

  • The study confirms the expression of p-AKT, p-mTOR, p-4E-BP1, and p-p70S6K in ALCL, with a higher incidence of ALK(+) cases.
  • An activated AKT/mTOR pathway is suggested in ALK(+) ALCL patients due to the correlation between ALK expression and the phosphorylation of AKT and mTOR.
  • Despite the observed pathway activation, the phosphorylation status of AKT and mTOR did not demonstrate obvious independent prognostic significance in this cohort.

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