Helicobacter pylori and mucosa-associated lymphoid tissue: what's new

Hematology Am Soc Hematol Educ Program. 2013:2013:109-17. doi: 10.1182/asheducation-2013.1.109.


Low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach, gastric MALT lymphoma, is associated with Helicobacter pylori infection. The eradication of H pylori using antibiotics is successful in 60% to 80% of affected patients. In contrast to the previous paradigm, we and other investigators have shown that a certain proportion of patients with H pylori-positive early-stage diffuse large B-cell lymphoma (DLBCL) of the stomach with histological evidence of MALT lymphoma, including high-grade transformed gastric MALT lymphoma and gastric DLBCL(MALT), achieved long-term complete pathological remission (pCR) after first-line H pylori eradication therapy, indicating that the loss of H pylori dependence and high-grade transformation are separate events in the progression of gastric lymphoma. In addition, patients with H pylori-positive gastric DLBCL without histological evidence of MALT (gastric pure DLBCL) may also respond to H pylori eradication therapy. A long-term follow-up study showed that patients who achieved pCR remained lymphoma free. Gastric MALT lymphoma is indirectly influenced by H pylori infection through T-cell stimulation, and recent studies have shown that H pylori-triggering chemokines and their receptors, H pylori-associated epigenetic changes, H pylori-regulated miRNA expression, and tumor infiltration by CD4+CD25+ regulatory T cells contribute to lymphomagenesis of gastric MALT lymphoma. Recent studies have also demonstrated that the translocation of CagA into B lymphocytes inhibits apoptosis through p53 accumulation, BAD phosphorylation, and the up-regulation of Bcl-2 and Bcl-XL expression. In gastric MALT lymphoma, CagA may stimulate lymphomagenesis directly, through the regulation of signal transduction, and intracellular CagA is associated with H pylori dependence. These findings represent a substantial paradigm shift compared with the classical theory of H pylori-reactive T cells contributing indirectly to the development of MALT lymphoma. In conclusion, a wide range of H pylori-related gastric lymphomas have been identified. The use of antibiotics as the sole first-line therapy for early-stage gastric pure DLBCL requires validation in a prospective study. The clinical and biological significance of the CagA oncoprotein in the lymphomagenesis of gastric MALT lymphoma warrants further study.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / metabolism*
  • Epigenesis, Genetic / immunology
  • Gastric Mucosa / immunology
  • Gastric Mucosa / metabolism*
  • Gastric Mucosa / microbiology
  • Helicobacter Infections / genetics
  • Helicobacter Infections / immunology
  • Helicobacter Infections / metabolism*
  • Helicobacter Infections / therapy
  • Helicobacter pylori / genetics
  • Helicobacter pylori / immunology
  • Helicobacter pylori / metabolism*
  • Humans
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / metabolism*
  • Lymphoid Tissue / microbiology
  • Lymphoma, B-Cell, Marginal Zone / genetics
  • Lymphoma, B-Cell, Marginal Zone / immunology
  • Lymphoma, B-Cell, Marginal Zone / metabolism*
  • Lymphoma, B-Cell, Marginal Zone / microbiology
  • Lymphoma, B-Cell, Marginal Zone / therapy
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / immunology
  • Lymphoma, Large B-Cell, Diffuse / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / microbiology
  • Lymphoma, Large B-Cell, Diffuse / therapy
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / microbiology
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / therapy
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / immunology
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-X Protein / genetics
  • bcl-X Protein / immunology
  • bcl-X Protein / metabolism


  • Anti-Bacterial Agents
  • BCL2L1 protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • bcl-X Protein