Telomere loss in Philadelphia-negative hematopoiesis after successful treatment of chronic myeloid leukemia: Evidence for premature aging of the myeloid compartment

Chiara Lobetti-Bodoni, Dario Ferrero, Elisa Genuardi, Roberto Passera, Elisa Bernocco, Daniela Sia, Giovanni Grignani, Elena Crisà, Luigia Monitillo, Alberto Rocci, Daniela Drandi, Valentina Giai, Manuela Zanni, Michela Boi, Gianluca Isaia, Daniela Barbero, Monia Lunghi, Elisabetta Abruzzese, Franca Radaelli, Massimo PiniPatrizia Pregno, Carmelo Carlo-Stella, Gianluca Gaidano, Mario Boccadoro, Marco Ladetto

Research output: Contribution to journalArticlepeer-review

Abstract

Telomere shortening, a well-known marker of aging and cellular stress, occurs under several conditions in the hematopoietic compartment, including aplastic anemia and following iatrogenic noxae. We decided to verify whether pathological telomere erosion also arises in restored Philadelphia-negative (Ph-negative) hematopoiesis following successful treatment of chronic myeloid leukemia (CML). Eighty-one CML patients in complete cytogenetic remission were compared to 76 age-matched healthy subjects. Myeloid cells of CML patients had shorter telomeres than controls (6521. bp vs 7233. bp, p<0.001). This difference was specific for the myeloid compartment, since it was not observed in lymphoid cells (6774. bp vs 6909. bp, p= 0.620). Acquired Ph-negative cytogenetic abnormalities (p= 0.010), lack of complete molecular remission (p= 0.016) and age (p= 0.013) were independent predictors of telomere shortening. Telomere dynamics were assessed over a median follow-up period of 22 months. We documented accelerated non-physiological ongoing telomere shortening in 17/59 CML patients (28%). Patients experiencing grade 2-4 hematological toxicity, during CML remission possessed significantly shorter telomeres compared to those lacking toxicity (p= 0.005 for any toxicity, p= 0.007 for anemia). CML patients suffer from significant and often ongoing telomere stress resulting in premature and selective aging of the myeloid compartment which might have long-term consequences on function and integrity of Ph-negative hematopoiesis.

Original languageEnglish
Pages (from-to)479-488
Number of pages10
JournalMechanisms of Ageing and Development
Volume133
Issue number7
DOIs
Publication statusPublished - Jul 2012

Keywords

  • Bone marrow failure
  • Cytogenetic abnormalities
  • Hematopoiesis
  • Telomere shortening
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Ageing
  • Developmental Biology

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