The Relevance of Telomerase and Telomere-Associated Proteins in B-Acute Lymphoblastic Leukemia

Genes (Basel). 2023 Mar 10;14(3):691. doi: 10.3390/genes14030691.

Abstract

Telomeres and telomerase are closely linked to uncontrolled cellular proliferation, immortalization and carcinogenesis. Telomerase has been largely studied in the context of cancer, including leukemias. Deregulation of human telomerase gene hTERT is a well-established step in leukemia development. B-acute lymphoblastic leukemia (B-ALL) recovery rates exceed 90% in children; however, the relapse rate is around 20% among treated patients, and 10% of these are still incurable. This review highlights the biological and clinical relevance of telomerase for B-ALL and the implications of its canonical and non-canonical action on signaling pathways in the context of disease and treatment. The physiological role of telomerase in lymphocytes makes the study of its biomarker potential a great challenge. Nevertheless, many works have demonstrated that high telomerase activity or hTERT expression, as well as short telomeres, correlate with poor prognosis in B-ALL. Telomerase and related proteins have been proven to be promising pharmacological targets. Likewise, combined therapy with telomerase inhibitors may turn out to be an alternative strategy for B-ALL.

Keywords: acute leukemia; hTERT; leukemia; telomerase; telomere.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Humans
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Telomerase* / genetics
  • Telomerase* / metabolism
  • Telomere / genetics
  • Telomere / metabolism
  • Telomere Shortening

Substances

  • Telomerase

Grants and funding

The authors receive fundings from the Brazilian Council for Scientific and Technological Development (CNPq), grant number 88887.501384/2020-00, and from the Fundação de Apoio à Pesquisa do Distrito Federal (FAPDF), grant numbers 00193-00001029/2021-95 and 00193-00000891/2021-81.