Progressive Telomere Shortening: An Epigenetic Biomarker of Chronic Myeloid Leukemia

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Progressive telomere shortening during successive cell divisions is thought to contribute to phase transition in chronic myeloid leukemia.
Progressive telomere shortening during successive cell divisions is thought to contribute to phase transition in chronic myeloid leukemia.

A group of European researchers has found an innovative way to determine telomere shortening at time of diagnosis in patients with chronic myeloid leukemia (CML), possibly providing a new, personalized way to evaluate and predict disease stage and its evolution in individuals.1

As the authors of the study noted, telomere shortening has previously been shown to be an indicator of disease stage, response to therapy, and progression. But differences between one person's telomere length and another's served as a barrier to its use as a prognostic tool for individual patients.

Authors of a recently published study, however, hypothesized that the relative length of an individual's telomeres at diagnosis could potentially serve as an epigenetic marker to predict the duration of chronic phase (CP) disease prior to the transition to acute phase or blast crisis.

“We compared TL of BCR-ABL, nonleukemic CD34+CD38 hematopoietic stem cells [HSC] in the bone marrow of CML patients at diagnosis to their individual BCR-ABL+ leukemic stem cell [LSC] counterparts,” the authors wrote. “We observed significantly accelerated telomere shortening in LSC compared with nonleukemic HSC.”1

The result, they wrote, showed that “accelerated telomere shortening was found to be correlated with an increasing leukemic clone size in the HSC compartment, a novel parameter that was previously shown to be correlated with prognosis and response to [tyrosine kinase inhibitor (TKI)] treatment.”

Previous studies have identified the importance of telomeres in the development of cancer.

“Telomeres maintain genomic integrity in normal cells, and their progressive shortening during successive cell divisions induces chromosomal instability,” according to a 2016 paper by researchers from the Center of Excellence in Genomic Medicine Research in Saudi Arabia.2 “In the large majority of cancer cells, telomere length is maintained by telomerase. Thus, telomere length and telomerase activity are crucial for cancer initiation and the survival of tumors.”

The association with cancer has led a number of researchers to look for ways to use telomeres and telomerase as both prognostic biomarkers and therapeutic targets.

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