Twenty years of modelling NPM-ALK-induced lymphomagenesis

Front Biosci (Schol Ed). 2015 Jun 1;7:236-47.

Abstract

Our current understanding of oncogenic Anaplastic Lymphoma Kinase (ALK)-induced lymphomagenesis has relied for over 20 years on multiple and complementary studies performed on various experimental models, encompassing ALK oncogene expressing cells, their grafts into immune-compromised mice, the generation of genetically engineered mouse models (GEMMs) and, when available, the use of patient samples from Anaplastic Large Cell Lymphoma (ALCL) tumour banks. Of note, and to our knowledge, no ALK-positive ALCL 3D culture system has been described so far. In this review, we will first outline how these different cell and mouse models were designed, and what key findings they revealed (or confirmed) towards oncogenic ALK-induced lymphomagenesis. Secondly, we will discuss how recent and revolutionary advances in genetic engineering technology are likely to complete our understanding of ALK-related disease in an effort to improve current therapeutic approaches.

Publication types

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

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Animals
  • Disease Models, Animal*
  • Humans
  • Lymphoma, Large-Cell, Anaplastic / enzymology*
  • Lymphoma, Large-Cell, Anaplastic / genetics*
  • Mice
  • Mice, Transgenic
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*

Substances

  • Nuclear Proteins
  • nucleophosmin
  • ALK protein, human
  • Alk protein, mouse
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases