CML treatment-free remission linked to telomere length
medwireNews: Preliminary research has uncovered a possible correlation between duration of treatment-free remission in patients with chronic myeloid leukaemia (CML) and their relative telomere length (RTL).
“The present study is the first to suggest that patients with longer telomeres would seem to be more susceptible to relapse after TKI [tyrosine kinase inhibitor] treatment”, say Giovanni Caocci, from the University of Cagliari in Italy, and co-workers.
The team studied 32 patients with chronic phase CML who had discontinued imatinib therapy after achieving a complete molecular response (CMR) for at least 18 months. In all, 41% of patients lost their CMR after a mean of 8.7 months but regained it after TKI therapy was restarted.
Real-time quantitative polymerase chain reaction assays revealed that median RTL was slightly shorter in the CML patients than in 32 age- and gender-matched healthy individuals, at 0.97 versus 1.05.
Age-corrected RTL was a median of 0.09 in the CML patients and was significantly shorter in those who continued to have a CMR after discontinuing TKI therapy than those who experienced molecular relapse, at a mean of 0.01 versus 0.20.
And when patients were stratified using the median age-corrected RTL of 0.09 or less, those with telomere length below the cutoff were significantly more likely to remain in treatment-free remission than individuals with longer telomeres, with rates of 78.9% and 30.8%, respectively.
Writing in a letter to the Journal of Hematology & Oncology, the researchers admit that their study is limited by the small number of patients and the absence of a longitudinal telomere assessment from diagnosis.
“A possible explanation is that quiescent CML stem cells harboring longer telomeres somehow manage to escape senescence mechanisms and maintain a proliferative potential even after discontinuation of imatinib treatment”, they say, adding that “this hypothesis should be supported by CML stem cell telomere assessment in patients with molecular response.”
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