Verkarre Virginie, Romana Serge-Pierrick, Cellier Christophe, Asnafi Vahid, Mention Jean-Jacques, Barbe Ullah, Nusbaum Sylvie, Hermine Olivier, Macintyre Elizabeth, Brousse Nicole, Cerf-Bensussan Nadine, Radford-Weiss Isabelle
INSERM EMI-0212, Faculté Necker-Université René Descartes-Paris V, France.
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.
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.
难治性乳糜泻是一种低度上皮内淋巴瘤，其特征为克隆性上皮内淋巴细胞扩增，细胞内有CD3ε，但无表面CD3 - T细胞受体复合物，它可能是乳糜泻与明显的T细胞淋巴瘤之间的中间阶段。为深入了解乳糜泻淋巴瘤发生的机制，我们首次对难治性乳糜泻进行了细胞遗传学研究。
对以下样本进行核型分析：（1）7株源自难治性乳糜泻患者克隆性上皮内淋巴细胞的细胞系；（2）14株对照T细胞系，其中4株来自7例难治性乳糜泻患者，10株来自无并发症的乳糜泻患者；（3）7例难治性乳糜泻患者中1例的骨髓和外周血淋巴细胞。通过使用全染色体涂染探针的原位杂交以及1例患者的比较基因组杂交来确认重排。
在7例难治性乳糜泻患者的细胞系中有6例发现了导致1号染色体长臂部分三体的复发性结构染色体畸变，而对照T细胞系中均未发现。在1例循环异常上皮内淋巴细胞的患者中，从骨髓和血液中新鲜分离的细胞上证实了1q部分三体。
难治性乳糜泻与1q区域的部分三体密切相关。1q染色体的获得最近在16%的肠病型T细胞淋巴瘤中发现，可能是与乳糜泻相关的淋巴瘤发生中的早期事件，并为研究该疾病中淋巴细胞转化的分子机制提供了关键线索。
