The new study built on earlier research by some of the same members of the research team that found that telomere shortening correlated with leukemic clone size (LSC), thereby providing evidence for determining whether the disease was in early or late CP.

It is an important determinant because of its effect on outcomes. “Patients in late CP have a higher LSC burden going along with an inferior response to TKI therapy.”3

And, while earlier studies had already established a correlation between telomere length and disease stage and duration of CP, the researchers still faced a major obstacle in applying those findings to specific patients.

As they explained in the 2016 study, “the high intra-individual, mostly genetic inter-individual variability in TL limits the predictive value of TL measurements when no patient-specific Bcr-Abl negative cells were available for comparison.”3

The comparison between telomere lengths in leukemic and nonleukemic stem cells, the authors of the new study wrote, addresses that problem. 

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And, while the investigators  acknowledged that the leukemic clone size reflects other factors besides the replicative history of the stem cells, they nonetheless concluded that the correlation between clone size and telomere length offers a new direction to pursue via research.

“The current data,” they wrote, “support the hypothesis that progressive telomere shortening represents an epigenetic biomarker of CML LSC, correlates with disease progression in CP, and (via increased genetic instability) contributes to phase transition of CML.”1

References

  1. Bouillon A-S, Ventura Ferreira MS, Awad SA, et al. Telomere shortening correlates with leukemic stem cell burden at diagnosis of chronic myeloid leukemiaBlood Adv. 2(13):1572-1579. doi: 10.1182/bloodadvances.2018017772
  2. Jafri MA, Ansari SA, Alqahtani MH, Shay JW. Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies. Genome Med. 2016;8(1):69. doi: 10.1186/s13073-016-0324-x
  3. Bouillon A-S, Ferreira MS, Awad SA, et al. Telomere length shortening in the CML leukemic stem cell compartment correlates with the respective clone size: evidence for early vs. late chronic phase. Blood. 2016;128:4243.