Epigenetic and Telomeric Regulations, Lyon Sud Medicine Faculty, Lyon-1 University, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 5239, Pierre Bénite, France.
Blood. 2011 Aug 4;118(5):1316-22. doi: 10.1182/blood-2010-07-295774. Epub 2011 Feb 25.
Cells of B-cell chronic lymphocytic leukemia (B-CLL) are characterized by short telomeres despite a low proliferative index. Because telomere length has been reported to be a valuable prognosis criteria, there is a great interest in a deep understanding of the origin and consequences of telomere dysfunction in this pathology. Cases of chromosome fusion involving extremely short telomeres have been reported at advanced stage. In the present study, we address the question of the existence of early telomere dysfunction during the B-CLL time course. In a series restricted to 23 newly diagnosed Binet stage A CLL patients compared with 12 healthy donors, we found a significant increase in recruitment of DNA-damage factors to telomeres showing telomere dysfunction in the early stage of the disease. Remarkably, the presence of dysfunctional telomeres did not correlate with telomere shortening or chromatin marks deregulation but with a down-regulation of 2 shelterin genes: ACD (coding for TPP1; P = .0464) and TINF2 (coding for TIN2; P = .0177). We propose that telomeric deprotection in the early step of CLL is not merely the consequence of telomere shortening but also of shelterin alteration.
B 细胞慢性淋巴细胞白血病（B-CLL）的细胞尽管增殖指数较低，但端粒却很短。由于端粒长度被认为是一个有价值的预后标准，因此人们对深入了解这种病理学中端粒功能障碍的起源和后果非常感兴趣。在晚期，已经报道了涉及极短端粒的染色体融合病例。在本研究中，我们探讨了在 B-CLL 病程中早期端粒功能障碍是否存在的问题。在一系列仅包括 23 例新诊断的 Binet 期 A CLL 患者与 12 例健康供体的比较中，我们发现招募到 DNA 损伤因子到显示疾病早期端粒功能障碍的端粒的数量显著增加。值得注意的是，功能失调的端粒的存在与端粒缩短或染色质标记失调无关，而是与 2 个庇护素基因的下调有关：ACD（编码 TPP1；P =.0464）和 TINF2（编码 TIN2；P =.0177）。我们提出，在 CLL 的早期阶段，端粒的去保护不仅是端粒缩短的结果，也是庇护素改变的结果。
