Refractory celiac sprue, a low-grade intraepithelial lymphoma characterized by expansion of clonal intraepithelial lymphocytes with intracellular CD3ϵ 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.

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.

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.

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.