Molecular pathogenesis of T-cell leukaemia and lymphoma

Nat Rev Immunol. 2008 May;8(5):380-90. doi: 10.1038/nri2304.

Abstract

T-cell acute lymphoblastic leukaemia (T-ALL) is induced by the transformation of T-cell progenitors and mainly occurs in children and adolescents. Although treatment outcome in patients with T-ALL has improved in recent years, patients with relapsed disease continue to have a poor prognosis. It is therefore important to understand the molecular pathways that control both the induction of transformation and the treatment of relapsed disease. In this Review, we focus on the molecular mechanisms responsible for disease induction and maintenance. We also compare the physiological progression of T-cell differentiation with T-cell transformation, highlighting the close relationship between these two processes. Finally, we discuss potential new therapies that target oncogenic pathways in T-ALL.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Differentiation
  • Cell Lineage
  • Child
  • F-Box Proteins / genetics
  • F-Box-WD Repeat-Containing Protein 7
  • Gene Expression Regulation, Leukemic*
  • Homeodomain Proteins / metabolism
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / genetics*
  • Leukemia-Lymphoma, Adult T-Cell / metabolism*
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Lymphoma / genetics*
  • Lymphoma / metabolism*
  • Lymphoma / pathology
  • Mice
  • Mutation
  • NF-kappa B / metabolism
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism
  • Signal Transduction*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*
  • Thymus Gland / growth & development
  • Thymus Gland / immunology
  • Transcription Factors / metabolism
  • Translocation, Genetic
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitination

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle Proteins
  • F-Box Proteins
  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • Homeodomain Proteins
  • NF-kappa B
  • Receptor, Notch1
  • Transcription Factors
  • Ubiquitin-Protein Ligases