Divergent Molecular Pathways Drive Monomorphic Epitheliotropic and Enteropathy-Associated Intestinal T-Cell Lymphoma

Strategic Insights -

Research from Lausanne University Hospital and University of Lausanne has identified the distinct genetic, epigenetic, and expression footprints of enteropathy-associated intestinal T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). The study, published in Leukemia, utilized whole-exome, RNA, and miRNA sequencing, and DNA methylation profiling to characterize the molecular specificities of these two lymphomas.

Key Takeaways:

  • The study found highly recurrent SETD2 loss-of-function alterations and frequent mutations of H3-3A/B in MEITL, while EATL harbored frequent mutations in TET2, ARID1A, and KMT2D.
  • Highly prevalent JAK-STAT pathway mutations preferentially affected JAK3 and STAT5B in MEITL, and JAK1 and STAT3 in EATL.
  • Half of EATLs contained disruptive mutations in HLA class I genes, impacting class I molecule expression.
  • EATLs containing more abundant macrophages were enriched in inflammatory response signatures, suggesting an immunosuppressive tumor microenvironment.
  • Unsupervised analyses of mutations, transcription, and methylation profiles concordantly segregated EATLs from MEITLs.

Statistics:

  • 30 EATLs and 52 MEITLs were analyzed in the study.
  • 50% of EATLs contained disruptive mutations in HLA class I genes.
  • JAK-STAT pathway mutations were found in 80% of MEITLs and 60% of EATLs.

Sources:

  • NewsRx. Findings on T-Cell Lymphoma Described by Researchers at Lausanne University Hospital and University of Lausanne (Divergent molecular pathways drive monomorphic epitheliotropic and enteropathy-associated intestinal T-cell lymphoma). Hematology Week. October 20, 2025; p 1656.
  • Leukemia. Divergent molecular pathways drive monomorphic epitheliotropic and enteropathy-associated intestinal T-cell lymphoma.