The role of telomerase catalytic subunit hTERT in clonal malignancies including human leukemia is fundamental in overcoming cell senescence and enabling prolonged proliferation. One direct transcriptional activator of hTERT is the oncogene MYC which is known to be, in turn, activated by JAK2. To explore the relationship of telomerase, MYC and JAK2 in chronic myeloproliferative diseases, we investigated hTERT and MYC expression in bone marrow cells of essential thrombocythemia (ET) and polycythemia vera (PV). We could determine an up-regulation of MYC expression exclusively in JAK2(wt) ET, whereas hTERT expression was rather inconsistent across the groups. Interestingly, a significant correlation between MYC and hTERT expression could only be established in homozygous JAK2(V617F) PV and control cases. Thus, the functional link between MYC and hTERT seems to be impaired depending on the molecular ET subtype, which in turn may have implications on the phenotype and course of the disease.
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http://dx.doi.org/10.1007/s00277-007-0424-1 | DOI Listing |
Adv Sci (Weinh)
December 2024
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.
Increased telomerase activity has been considered as a conspicuous sign of human cancers. The catalytic cores of telomerase involve a reverse transcriptase and the human telomerase RNA (hTR). However, current detection of telomerase is largely limited to its activity at the tissue and single-cell levels.
View Article and Find Full Text PDFBioorg Med Chem Lett
December 2024
Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, HarBin Medical University, Harbin, PR China. Electronic address:
The telomeric G-quadruplex (G4) along with the telomerase catalytic subunit hTERT are crucial in the extension of telomeres. Tumor cells can establish replicative immortality by activating the telomere-maintenance mechanism (TMM).Small molecule ligands can limit cancer telomere lengthening by by targeting at G4 and hTERT.
View Article and Find Full Text PDFCancer Cell Int
December 2024
Department of Chemistry, Lahijan Branch, Islamic Azad University, Lahijan, Iran.
Telomerase, an enzyme crucial for maintaining telomere length, plays a critical role in cellular immortality and is overexpressed in most cancers. This ubiquitous presence makes telomerase, and specifically its catalytic subunit, human telomerase reverse transcriptase (hTERT), an attractive target for cancer immunotherapy. This review explores the development and application of telomerase-based vaccines, focusing on DNA and peptide-based approaches.
View Article and Find Full Text PDFJ Biomol Struct Dyn
December 2024
Laboratory of Molecular Modeling and Anticancer Drug Development. Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
In about 85% of cancer malignancies, replicative immortality caused by increased telomerase activity makes it an attractive target for developing anticancer therapeutics. However, the lack of approved small-molecule inhibitors rooted in the structural ambiguity of telomerase has impeded drug development for decades. In this study, we have exploited the FVYL pocket in the thumb domain, which plays a key role in the enzyme's processivity.
View Article and Find Full Text PDFCancer Cell Int
December 2024
Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, 440 Ji- Yan Road, Jinan, 250117, Shandong Province, PR China.
Background: Telomerase reverse transcriptase (TERT) is a catalytic subunit of telomerase and required for cancer development. This study aims to reveal its clinical utility for diagnosis and prognosis of resectable NSCLC.
Methods: TERT was quantitatively evaluated by the enzyme-linked immunosorbent assay (ELISA) from 69 patients before and after the surgery.
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