Correlation of telomerase activity to apoptosis and survival in adult acute lymphoblastic leukemia: an Egyptian single-center study

Abstract

Telomerase is activated in most tumors, but suppressed in normal human somatic cells. Current evidence indicates that telomerase reactivation is a critical step in carcinogenesis, with a close relationship to apoptosis. The goal of this study was to investigate the levels and relationship of telomerase activity to apoptosis and its impact on the survival of Egyptian adult acute lymphoblastic leukemia patients. Telomerase activity was quantified by polymerase chain reaction (PCR) and detected by enzyme-linked immunosorbent assay (ELISA), while apoptosis was measured at the single-cell level by fluorescence in situ detection using flow cytometry in 15 control subjects and 40 acute lymphoblastic leukemia (ALL) patients at presentation. Telomerase activity in ALL patients was negatively correlated to apoptosis [percent and mean fluorescence intensity (MFI)] (p < 0.001 for percent and p < 0.001 for MFI) and to the 4-year survival rate (p < 0.05), to which apoptosis (percent and MFI) was consequently positively correlated (p < 0.001 for percent and p < 0.05 for MFI). For telomerase, the highest positive predictive value (PPV) for mortality (93.3%) was at a cut-off value of 13 amol/ml, while those for apoptosis (85% for percent of apoptotic cells and 90.9% for MFI) were at a cut-off of 8% and 0.19 MFI. This makes the measurement of telomerase activity in ALL patients a potential tool to predict disease with unfavorable outcome and a candidate tumor marker.

The role of telomeres and telomerase in hematologic malignancies and hematopoietic stem cell transplantation

“…The telomerase activity of ALL cells has been reported to be higher in male patients with than in female patients. This may be due to the negative regulatory function of estrogen on telomerase [ 20 ].…”

“…Asfour et al . reported that apoptosis of the leukemic blasts was blocked by telomerase in ALL patients, resulting in an increased tumor burden, faster disease progression and shortened survival [ 20 ]. Telomerase activities in ALL patients correlated to the enzyme concentration of lactate dehydrogenase (LDH), which is an adverse prognostic factor in ALL patients [ 20 ].…”

Methylation of CDKN2B CpG islands is associated with upregulated telomerase activity in children with acute lymphoblastic leukemia

“…Swellam et al (17) demonstrated that laryngeal squamous cell carcinoma progression was associated with an increase in telomerase activity; however, deletion of the CDKN2A and CDKN2B genes may assist in the prognosis and improved classification of patients for treatment. Other previous studies have indicated the importance of CDKN2B methylation and upregulated telomerase activity in the development of ALL (18–20). Therefore, in the present study, the association of CDKN2B methylation with telomerase activity in childhood ALL, and the association of alterations in CDKN2B methylation and telomerase activity with clinicopathological data from children with ALL were investigated.…”

Telomerase‐based therapies in haematological malignancies

“…Furthermore, TA in male ALL patients was higher than in female patients, which can be caused by the regulatory impact of some signals such as ultraviolet radiation, alpha‐interferon and oestrogen 101 . Also, enzyme concentration of lactate dehydrogenase was positively associated with telomerase activities in ALL patients as a prognostic factor of the severity of disease 102 . Alterations in the expression of shelterin proteins have been reported in ALL patients.…”

“…101 Also, enzyme concentration of lactate dehydrogenase was positively associated with telomerase activities in ALL patients as a prognostic factor of the severity of disease. 102 Alterations in the expression of shelterin proteins have been reported in ALL patients. In this regard, the TRF2 was 8-to 10-fold higher in B-ALL than in T-ALL, AML, or control BMMNCs, as well as the expression level of TRF2, was 10-fold higher in B-ALL with abnormal karyotype than in forms without cytogenetic abnormality.…”