Pathogenesis of human B cell lymphomas

Annu Rev Immunol. 2012;30:565-610. doi: 10.1146/annurev-immunol-020711-075027. Epub 2012 Jan 6.

Abstract

The mechanisms that drive normal B cell differentiation and activation are frequently subverted by B cell lymphomas for their unlimited growth and survival. B cells are particularly prone to malignant transformation because the machinery used for antibody diversification can cause chromosomal translocations and oncogenic mutations. The advent of functional and structural genomics has greatly accelerated our understanding of oncogenic mechanisms in lymphomagenesis. The signaling pathways that normal B cells utilize to sense antigens are frequently derailed in B cell malignancies, leading to constitutive activation of prosurvival pathways. These malignancies co-opt transcriptional regulatory systems that characterize their normal B cell counterparts and frequently alter epigenetic regulators of chromatin structure and gene expression. These mechanistic insights are ushering in an era of targeted therapies for these cancers based on the principles of pathogenesis.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Epigenesis, Genetic
  • Humans
  • Immune Evasion
  • Lymphoma, B-Cell / drug therapy
  • Lymphoma, B-Cell / etiology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Oncogene Proteins / antagonists & inhibitors
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Signal Transduction / drug effects
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Antineoplastic Agents
  • MicroRNAs
  • Oncogene Proteins
  • Transcription Factors