Recurrent partial trisomy 1q22-q44 in clonal intraepithelial lymphocytes in refractory celiac sprue

Gastroenterology. 2003 Jul;125(1):40-6. doi: 10.1016/s0016-5085(03)00692-9.


Background & aims: Refractory celiac sprue, a low-grade intraepithelial lymphoma characterized by expansion of clonal intraepithelial lymphocytes with intracellular CD3 epsilon but no surface CD3-T-cell receptor complexes, can be an intermediary step between celiac disease and overt T-cell lymphoma. To gain insight into the mechanisms of lymphomagenesis in celiac disease, we have performed the first cytogenetic study in refractory celiac sprue.

Methods: Karyotypes were performed on: (1) 7 cell lines derived from clonal intraepithelial lymphocytes of patients with refractory celiac sprue; (2) 14 control T-cell lines, either from 4 of 7 patients with refractory celiac sprue or from 10 patients with uncomplicated celiac disease; and (3) bone marrow and peripheral blood lymphocytes in 1 of 7 patients with refractory celiac sprue. Rearrangements were confirmed by in situ hybridization using whole-chromosome painting probes and by comparative genomic hybridization in one patient.

Results: A recurrent structural chromosomal aberration leading to partial trisomy of the long arm of chromosome 1 was found in 6 of 7 cell lines from patients with refractory celiac sprue but in none of the control T-cell lines. In one patient with circulating abnormal intraepithelial lymphocytes, the partial trisomy 1q was confirmed on cells freshly isolated from bone marrow and blood.

Conclusions: Refractory celiac sprue is strongly associated with partial trisomy of the 1q region. Gain of chromosome 1q, recently found in 16% of enteropathy-type T-cell lymphoma, may be an early event in lymphomagenesis related to celiac disease and provides a key to investigating molecular mechanisms of lymphoid transformation in this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Celiac Disease / genetics*
  • Celiac Disease / immunology
  • Cell Line
  • Chromosomes, Human, Pair 1*
  • Clone Cells
  • Female
  • Gene Rearrangement
  • Genes, T-Cell Receptor gamma
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Lymphocytes / cytology*
  • Lymphocytes / immunology
  • Male
  • Middle Aged
  • Recurrence
  • Trisomy*