Molecular underpinning of extranodal NK/T-cell lymphoma

Best Pract Res Clin Haematol. 2013 Mar;26(1):57-74. doi: 10.1016/j.beha.2013.04.006. Epub 2013 May 23.


Peripheral NK/T-cell lymphoma (PTCL) is a heterogeneous group of uncommon hematologic malignancies with aggressive clinical course and unfavorable prognosis. Extranodal NK/T-cell lymphoma, nasal type (NKTCL) is the most common extranodal entity worldwide, with heterogeneous geographic distribution, and it is characterized by its association with EBV, a nasal or less often extranasal presentation and aggressive behavior. Recent works using array-based technologies have provided novel insights into the pathogenesis and discovered new biomarkers with diagnostic and therapeutic implications in NKTCL. Gene expression profiling identified that most of the NKTCL are derived from activated natural killer cells with distinctively high expression of granzyme H compared to other PTCLs, which might serve as a new diagnostic biomarker. Frequent deletions and promoter methylations in PRDM1, ATG5, AIM1, FOXO3, HACE1 mapping to 6q21-q25, suggest their roles as potential tumor suppressors. The deregulation of oncogenic pathways (PDGF, JAK-STAT, AKT) provides a rationale for developing targeted therapies in the future.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • DNA Methylation
  • Gene Expression Regulation, Neoplastic
  • Granzymes / genetics*
  • Granzymes / metabolism
  • Humans
  • Lymphoma, Extranodal NK-T-Cell / drug therapy
  • Lymphoma, Extranodal NK-T-Cell / genetics*
  • Lymphoma, Extranodal NK-T-Cell / metabolism
  • Lymphoma, Extranodal NK-T-Cell / pathology
  • Lymphoma, T-Cell, Peripheral / drug therapy
  • Lymphoma, T-Cell, Peripheral / genetics*
  • Lymphoma, T-Cell, Peripheral / metabolism
  • Lymphoma, T-Cell, Peripheral / pathology
  • Molecular Targeted Therapy
  • Natural Killer T-Cells / drug effects
  • Natural Killer T-Cells / pathology
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Signal Transduction


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Neoplasm Proteins
  • GZMH protein, human
  • Granzymes