Dynamics of telomere's length and telomerase activity in Philadelphia chromosome negative myeloproliferative neoplasms

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• 作者：Emmanouil Spanoudakis^a ; Ioanna Bazdiara^a ; Despoina Pantelidou^a ; Ioannis Kotsianidis^a ; Vasilios Papadopoulos^b ; Dimitrios Margaritis^a ; George Xanthopoulidis^a ; Eleftherios Moustakidis^a ; Stamatia Mantzourani^a ; George Bourikas^a ; Costas Tsatalas^a ; ^{ktsatala@med.duth.gr}
• 关键词：Ph^negMPN ; JAK2V617F ; Telomeres ; Telomerase Activity
• 刊名：Leukemia Research
• 出版年：2011
• 出版时间：April 2011
• 年：2011
• 卷：35
• 期：4
• 页码：459-464
• 全文大小：496 K

文摘

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^negMPN'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^negMPN'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^negMPN subgroups compared to healthy donors. Moreover, TL below the cut-off value of 27 % could predict disease progression in Ph^negMPN patients (PFS at 5 years 39 % vs 81 % ). Thus, TL emerges as a new prognostic marker in Ph^negMPN, reflecting probably the genetic instability of highly proliferating MPN clones.