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

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.

► The myeloid population of CML patients displayed significantly shorter TL.
► TL shortening was more pronounced in patients with CA or without CMolR.
► TL of Ph-negative cells displayed no recovery over time.
► There is an association between short telomeres and hematological toxicity.
► TL stress results in premature aging of the myeloid compartment.