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

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.