The molecular pathogenesis of B-cell non-Hodgkin lymphoma

Eur J Haematol. 2015 Oct;95(4):280-93. doi: 10.1111/ejh.12589. Epub 2015 Jun 9.

Abstract

The B-cell non-Hodgkin lymphomas (B-NHL) are a diverse group of haematological malignancies which arise from the mature B-lymphocyte compartment. Recently, our understanding of the molecular pathogenesis of these disorders has greatly increased due to technological advances such as high-throughput DNA sequencing techniques. A paradigm of B-NHL pathogenesis has emerged where the normal genetic processes that are central to generating B-cell receptor diversity (somatic hypermutation and class switch/VDJ recombination) also drive the genesis of large-scale, chromosomal-level genetic lesions and smaller-scale gene-level mutations to produce the malignant phenotypes observed. Whilst a significant degree of genetic heterogeneity exists within each B-NHL subtype, the genetic lesions present within each subtype show a degree of convergence on common intracellular signalling, epigenetic and cell cycle pathways. This convergence gives an insight into the key oncogenic drivers of specific B-NHL subtypes and potential targets for therapeutic intervention. This review covers the current understanding of the causative genetic processes of B-NHL, the associated driving molecular lesions and the implications of these findings for the treatment of this group of disorders.

Keywords: Non Hodgkin lymphoma; molecular; next generation sequencing.

Publication types

  • Review

MeSH terms

  • Animals
  • Chromosome Aberrations
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Lymphoma, B-Cell / etiology*
  • Lymphoma, B-Cell / metabolism*
  • Lymphoma, B-Cell / therapy
  • Lymphoma, Non-Hodgkin / etiology*
  • Lymphoma, Non-Hodgkin / metabolism*
  • Lymphoma, Non-Hodgkin / therapy
  • Mutation
  • Oncogenes / genetics