title: Telomere shortening in Ph-negative chronic myeloproliferative neoplasms: a biological marker of polycythemia vera and myelofibrosis, regardless of hydroxycarbamide therapy.
abstract: The purpose of this study was to investigate telomere length (TL) in Ph-negative chronic myeloproliferative neoplasms (Ph-neg-CMNs), and the possible association of TL with disease progression and hydroxycarbamide (HU) treatment. TL was analyzed in peripheral blood samples from 239 patients with Ph-neg-CMNs, including polycythemia vera (PV), essential thrombocythemia and myelofibrosis (MF), and compared with age-matched healthy control subjects (CTR), along with some cases of secondary erythrocytosis (SE). More than half of the patients with CMN received at least 1 year of cytoreduction, mainly HU, before TL analysis. JAK2 mutation analysis was performed as well. TL was significantly shortened in patients with CMN compared with CTR (p < 0.0001). PV and MF showed the most pronounced decrease (p < 0.0001), whereas both essential thrombocythemia and SE showed no significant difference in TL compared with CTR. A short TL correlated with JAK2-V617F allele burden greater than 50% (p = 0.0025), age (p = 0.0132) and diagnosis of PV (p = 0.0122). No correlation was found with disease duration, history of thrombosis, cytoreductive treatment, antiaggregation agents, adverse cytogenetics, phlebotomies, or time to evolution to MF. In summary, TL is distinctly shortened in PV and MF, and it inversely correlates with JAK2V617F allele burden. In addition, HU is unlikely to contribute to telomere erosion. Lastly, PV and SE significantly differ in TL. Therefore, TL could be an additional diagnostic marker to identify and monitor Ph-neg-CMN patients.
authors.affiliation: Haematology and Cell Therapy Unit, Azienda Ospedaliera Ordine Mauriziano, Torino, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ruella
authors.forename: Silvia
authors.initials: S
authors.lastname: Salmoiraghi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Risso
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carobbio
authors.forename: Stefano
authors.initials: S
authors.lastname: Buttiglieri
authors.forename: Tiziana
authors.initials: T
authors.lastname: Spatola
authors.forename: Piera
authors.initials: P
authors.lastname: Sivera
authors.forename: Irene
authors.initials: I
authors.lastname: Ricca
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
authors.forename: Corrado
authors.initials: C
authors.lastname: Tarella
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells / Q000473:pathology; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009196:Myeloproliferative Disorders / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D011086:Polycythemia / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D011087:Polycythemia Vera / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D055728:Primary Myelofibrosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D016615:Telomere / Q000648:ultrastructure*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D006918:Hydroxyurea