Telomere Length and Hematological Disorders: A Review

Abstract

Telomeres compose the end portions of human chromosomes, and their main function is to protect the genome. In hematological disorders, telomeres are shortened, predisposing to genetic instability that may cause DNA damage and chromosomal rearrangements, inducing a poor clinical outcome. Studies from 2010 to 2019 were compiled and experimental studies using samples of patients diagnosed with hematological malignancies that reported the size of the telomeres were described. Abnormal telomere shortening is described in cancer, but in hematological neoplasms, telomeres are still shortened even after telomerase reactivation. In this study, we compared the sizes of telomeres in leukemias, myelodysplastic syndrome and lymphomas, identifying that the smallest telomeres are present in patients at relapse. In conclusion, the experimental and clinical data analyzed in this review demonstrate that excessive telomere shortening is present in major hematological malignancies and its analysis and measurement is a crucial step in determining patient prognosis, predicting disease risk and assisting in the decision for targeted therapeutic strategies.

Keywords: Telomere length; cancer; hematological disorders; review.

Figure 1. Hematopoietic stem cells express intrinsic telomerase activity which is required to sustain their accelerated replication cycle. When telomerase activity is lacking hematopoietic stem cells become unstable, leading to DNA damage and consequent bone marrow failure (5).

Figure 2. Telomerase enzyme counteracts nucleotide loss during cell replication. The catalytic domain has telomerase reverse transcriptase (TERT) activity, which utilizes the telomerase mRNA (TERC) subunit as a complementary template for the addition of nucleotides to telomeric DNA. The Shelterin complex is composed of six proteins (POT1, TPP1, TRF1, TRF2, TIN2 and Rap1) responsible for maintaining genetic integrity, assisting in the prevention of excessive DNA damage and regulating telomere-telomerase interaction. The complex protects telomeric DNA from unwanted degradation and chromosomal fusions (13).