Telomerase‐based therapies in haematological malignancies

Rafat, Ali; Asl, Khadijeh Dizaji; Mazloumi, Zeinab; Movassaghpour, Ali Akbar; Farahzadi, Raheleh; Nejati, Babak; Charoudeh, Hojjatollah Nozad

doi:10.1002/cbf.3687

Cited by 10 publications

(5 citation statements)

References 155 publications

(289 reference statements)

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“…The multi-functional profile of telomerase, as well as its relevance for carcinogenesis and cancer maintenance, make it an extremely relevant target for the development of studies focusing on both therapeutical purposes and on the understanding of tumor biology, especially in blood-related diseases [ 167 , 168 , 169 ].…”

Section: Discussionmentioning

confidence: 99%

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

Mota

Camargo

Biojone

et al. 2023

Genes

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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.

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Section: Discussionmentioning

confidence: 99%

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

Mota

Camargo

Biojone

et al. 2023

Genes

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“…Telomeres have another crucial function. For each cell cycle, a loss of nucleotide base pairs occurs during DNA replication, and when telomeres reach a certain length, the cell escapes the cell cycle, triggering senescence or apoptosis [36]. Yet, a small fraction of cell types (germ cells, cancer cells, and stem cells) can reverse increasing telomere shortening by activating the so-called "Telomere Maintenance Mechanisms (TMMs)" that can preserve TL [37].…”

Section: Function Of Telomerementioning

confidence: 99%

Involvement of Inheritance in Determining Telomere Length beyond Environmental and Lifestyle Factors

Gold,

Okeke,

2023

Aging and disease

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All linear chromosomal ends have specific DNA-protein complexes called telomeres. Telomeres serve as a "molecular clock" to estimate the potential length of cell replication. Shortening of telomere length (TL) is associated with cellular senescence, aging, and various age-related diseases in humans. Here we reviewed the structure, function, and regulation of telomeres and the age-related diseases associated with telomere attrition. Among the various determinants of TL, we highlight the connection between TL and heredity to provide a new overview of genetic determinants for TL. Studies across multiple species have shown that maternal and paternal TL influence the TL of their offspring, and this may affect life span and their susceptibility to age-related diseases. Hence, we reviewed the linkage between TL and parental influences and the proposed mechanisms involved. More in-depth studies on the genetic mechanism for TL attrition are needed due to the potential application of this knowledge in human medicine to prevent premature frailty at its earliest stage, as well as promote health and longevity.

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“…Telomerase is a reverse transcriptase enzyme that protects telomeres (the ends of chromosomes) from erosion and makes genomic stability. 7 Telomerase consists of two subunits including hTERT (catalytic unit) and TERC (RNA template). 8 , 9 Telomerase activity is associated with the expression of hTERT and causes poor prognosis of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Telomerase and mitochondria inhibition promote apoptosis and TET2 and ANMT3a expression in triple negative breast cancer cell lines

Mazloumi,

Rafat,

Dizaji Asl

et al. 2023

Bioimpacts

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Introduction: High metastasis, resistance to common treatments, and high mortality rate, has made triple-negative breast cancer (TNBC) to be the most invasive type of breast cancer. High telomerase activity and mitochondrial biogenesis are involved in breast cancer tumorigenesis. The catalytic subunit of telomerase, telomerase reverse transcriptase (hTERT), plays a role in telomere lengthening and extra-biological functions such as gene expression, mitochondria function, and apoptosis. In this study, it has been aimed to evaluate intrinsic-, extrinsic-apoptosis and DNMT3a and TET2 expression following the inhibition of telomerase and mitochondria respiration in TNBC cell lines. Methods: TNBC cells were treated with IC50 levels of BIBR1532, tigecycline, and also their combination. Then, telomere length, and DNMT3a, TET2, and hTERT expression were evaluated. Finally, apoptosis rate, apoptosis-related proteins, and genes were analyzed. Results: The present results showed that IC50 level of telomerase and inhibition of mitochondria respiration induced apoptosis but did not leave any significant effect on telomere length. The results also indicated that telomerase inhibition induced extrinsic-apoptosis in MDA-MB-231 and caused intrinsic- apoptosis in MDA-MB-468 cells. Furthermore, it was found that the expression of p53 decreased and was ineffective in cell apoptosis. The expressions of DNMT3a and TET2 increased in cells. In addition, combination treatment was better than BIBR1532 and tigecycline alone. Conclusion: The inhibition of telomerase and mitochondria respiration caused intrinsic- and extrinsic- apoptosis and increased DNMT3a and TET2 expression and it could be utilized in breast cancer treatment.

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Telomerase‐based therapies in haematological malignancies

Cited by 10 publications

References 155 publications

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

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

Involvement of Inheritance in Determining Telomere Length beyond Environmental and Lifestyle Factors

Telomerase and mitochondria inhibition promote apoptosis and TET2 and ANMT3a expression in triple negative breast cancer cell lines

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