Division d'Hématologie, CHUS, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Ann Anat. 2010 Sep 20;192(5):302-8. doi: 10.1016/j.aanat.2010.07.006. Epub 2010 Aug 6.
Recent research using an innovative 3D quantitative FISH approach of nuclear remodelling associated with the transition from mononuclear Hodgkin to diagnostic multinuclear Reed-Sternberg cells revealed profound changes in the 3D nuclear organization of telomeres. Analogous 3D telomere dynamics were identified in Hodgkin's lymphoma derived cell-lines and diagnostic patient biopsies. These changes were observed in both, EBV positive and EBV-negative Hodgkin's lymphoma and independent of the age of the patients at presentation. Compared to mononuclear Hodgkin cells, multinuclear Reed-Sternberg cells are characterized by a highly significant increase of telomere aggregates, often composed of very short telomeres, telomere shortening and loss. RS-cells with telomere free "ghost" nuclei are regularly observed. The telomere protecting shelterin complex appears to be disrupted and deregulation of DNA-repair mechanisms is observed. Our findings are consistent with the hypothesis that distinct 3D telomere changes and shelterin disruption represent a common pathogenetic denominator in the generation of Reed-Sternberg cells.
最近的研究采用了一种创新的 3D 定量荧光原位杂交（FISH）方法，研究了与单核霍奇金细胞向诊断性多核里德-斯特恩伯格（Reed-Sternberg）细胞过渡相关的核重构，揭示了端粒 3D 核构象的深刻变化。在霍奇金淋巴瘤衍生的细胞系和诊断性患者活检中也发现了类似的 3D 端粒动力学。这些变化在 EBV 阳性和 EBV 阴性霍奇金淋巴瘤中均观察到，且与患者就诊时的年龄无关。与单核霍奇金细胞相比，多核里德-斯特恩伯格细胞的端粒聚集体显著增加，这些聚集体通常由非常短的端粒组成，端粒缩短和丢失。经常观察到没有端粒的“幽灵”核的 RS 细胞。端粒保护的庇护素复合物似乎被破坏，并且观察到 DNA 修复机制的失调。我们的研究结果与以下假设一致，即不同的 3D 端粒变化和庇护素破坏是里德-斯特恩伯格细胞产生的共同发病机制。
