Telomerase (hTERT) Overexpression Reveals a Promising Prognostic Biomarker and Therapeutical Target in Different Clinical Subtypes of Pediatric Acute Lymphoblastic Leukaemia

Abstract

Acute Lymphoblastic Leukemia (ALL) is a neoplasm of the hematopoietic system defined as a clonal expansion of an abnormal lymphoid precursor cell. It mostly affects children under five years of age and is the most common tumor to afflict pediatric patients. The expression of the human telomerase gene (hTERT) in patients with ALL has been studied as a biomarker and could become a new therapeutic target. We evaluate the role of hTERT gene expression in ALL pediatric patients, through quantitative real-time PCR technique, and the possible correlation between hTERT expression and clinical variables: gender, age, white blood cells (WBC), gene fusions, and immunophenotyping. The analysis between healthy controls and ALL patients (N = 244) was statistically significant (p < 0.001), demonstrating hTERT overexpression in these patients. In comparison with the usual set of clinical variables, the data were not statistically significant (p > 0.05), indicating that hTERT is equally overexpressed among patients regardless of gender, age, gene fusions, and immunophenotyping. Moreover, patients who presented a higher hTERT expression level had a significant (p < 0.0001) lower overall survival rate. In summary, hTERT expression emerges as an important molecular pathway in leukemogenesis regardless patient’s clinical variables, thus, the data here presented pointed it as a valuable biomarker in pediatric acute lymphoblastic leukemia and a promising target for new therapeutic and prognostic measures.

Genetically predicted telomere length and the risk of 11 hematological diseases: a Mendelian randomization study

“…There have been numerous studies on the relationship between TL and the prognosis of ALL. In B-ALL patients, high telomerase activity, elevated telomere reverse transcriptase (TERT) expression, and telomere shortening were closely associated with poor prognosis [ 20 , 21 ]. However, some studies have also found that telomere elongation was linked to poor prognosis in ALL [ 22 ].…”

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

“…Moreover, small telomere and telomerase activities have been reported as potential biomarkers in different oncological patients [ 42 , 43 , 44 ]. Furthermore, telomere maintenance and hTERT expression are being considered as potential targets in leukemia [ 45 , 46 , 47 ]. In this context, the relevance of using biomarkers to understand B-acute lymphoblastic leukemia, as well as for guiding therapies, is evident.…”

“…Telomerase can block apoptosis mechanisms in leukemic blasts, resulting in faster disease progression, and its activities are related with lactate dehydrogenase, which is an unfavorable prognostic factor for ALL patients [ 166 ]. In this sense, recent studies have revealed telomerase overexpression and hTERT methylation status as a promising prognostic biomarkers in B-ALL (especially for childhood disease), and more precisely for maintenance and disease persistence, also reinforcing the potential of telomerase as therapeutical target, mainly due to its multiple non-canonical actions [ 45 , 47 , 179 ].…”

“…In this sense, it was demonstrated that quantification of telomerase expression along with monitoring MRD by qPCR can strengthen the follow up of patients with B-ALL. This would not only improve treatment follow up but also help to identify post-therapy remission [ 47 ].…”

The Role of WRAP53 in Cell Homeostasis and Carcinogenesis Onset

“…WRAP53 implication in leukemias was suggested by Nogueira et al [ 82 ], in which the overexpression of TERT in patients with acute lymphoblastic leukemia (ALL) proved to be a common biomarker indifferent to the ALL subtype. In addition, WRAP53 showed a strong interaction with TERT in a protein–protein interaction (PPI) network.…”