Department of Haematology, Democritus University of Thrace, Medical School, Alexandroupolis, Greece.
Leuk Res. 2011 Apr;35(4):459-64. doi: 10.1016/j.leukres.2010.07.042. Epub 2010 Sep 9.
Telomere exhaustion and increased telomerase activity are associated with the acquisition of aggressive molecular events in a variety of haematological malignancies. In Philadelphia chromosome negative myeloproliferative neoplasms (Ph(neg)MPN's), telomere dynamics during clonal evolution of these diseases have not yet been fully elucidated. Herein we demonstrated that telomere shortening is a global phenomenon in Ph(neg)MPN's, irrespective of disease phenotype, treatment administration and JAK2V617F mutational status but the presence of additional cytogenetic abnormalities further affects them. Consistent with the above finding, TA was upregulated in CD34+ haemopoietic progenitors from almost all Ph(neg)MPN subgroups compared to healthy donors. Moreover, TL below the cut-off value of 27% could predict disease progression in Ph(neg)MPN patients (PFS at 5 years 39% vs 81%). Thus, TL emerges as a new prognostic marker in Ph(neg)MPN, reflecting probably the genetic instability of highly proliferating MPN clones.
端粒耗竭和端粒酶活性增加与各种血液恶性肿瘤中侵袭性分子事件的获得有关。在费城染色体阴性骨髓增殖性肿瘤（Ph(neg)MPN）中，这些疾病克隆进化过程中端粒动力学尚未完全阐明。本研究表明，端粒缩短是 Ph(neg)MPN 的一种普遍现象，与疾病表型、治疗管理和 JAK2V617F 突变状态无关，但存在其他细胞遗传学异常进一步影响端粒缩短。与上述发现一致，与健康供体相比，几乎所有 Ph(neg)MPN 亚组的 CD34+造血祖细胞中 TA 均上调。此外，TL 低于 27%的截断值可预测 Ph(neg)MPN 患者的疾病进展（5 年 PFS 为 39% vs 81%）。因此，TL 成为 Ph(neg)MPN 的一个新的预后标志物，可能反映了高度增殖性 MPN 克隆的遗传不稳定性。
