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 (6521bp vs 7233bp, p<0.001). This difference was specific for the myeloid compartment, since it was not observed in lymphoid cells (6774bp vs 6909bp, 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.
Telomere loss in Philadelphia-negative hematopoiesis after successful treatment of chronic myeloid leukemia : evidence for premature aging of the myeloid compartment / C. Lobetti Bodoni, D. Ferrero, E. Genuardi, R. Passera, E. Bernocco, D. Sia, G. Grignani, E. Crisà, L. Monitillo, A. Rocci, D. Drandi, V. Giai, M. Zanni, M. Boi, G. Isaia, D. Barbero, M. Lunghi, E. Abruzzese, F. Radaelli, M. Pini, P. Pregno, C. Carlo Stella, G. Gaidano, M. Boccadoro, M. Ladetto. - In: MECHANISMS OF AGEING AND DEVELOPMENT. - ISSN 0047-6374. - 133:7(2012 Jul), pp. 479-488.
|Titolo:||Telomere loss in Philadelphia-negative hematopoiesis after successful treatment of chronic myeloid leukemia : evidence for premature aging of the myeloid compartment|
|Parole Chiave:||Bone marrow failure; Cytogenetic abnormalities; Hematopoiesis; Telomere shortening; Tyrosine kinase inhibitors|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
Settore MED/15 - Malattie del Sangue
|Data di pubblicazione:||lug-2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.mad.2012.05.007|
|Appare nelle tipologie:||01 - Articolo su periodico|