https://reports.sci.am/index.php/reports <p><em data-start="0" data-end="19">Reports of NAS RA</em> (REPNAS) is a peer‑reviewed, open‑access journal of the National Academy of Sciences of Armenia that publishes high‑quality research across all STEM disciplines.</p> <p>REPNAS welcomes Original Research Articles, Review Articles, Short Research Papers, Letters, and Editorials that deliver solid and sound contributions, robust methodologies, and multidisciplinary insights of relevance to the global scientific community.</p> "GITUTYUN" PUBLISHING HOUSE OF NAS RA en-US Reports of NAS RA 3045-3151 https://reports.sci.am/index.php/reports/article/view/55 <p>Telomere maintenance is a defining requirement of malignant cells, which must counteract the progressive telomere attrition that otherwise drives replicative senescence. Two principal telomere maintenance mechanisms (TMM) have been characterized: the telomerase-dependent mechanism (TEL), which reactivates the telomerase ribonucleoprotein to add telomeric repeats, and the alternative lengthening of telomeres (ALT), a homologous-recombination-based, telomerase-independent pathway. Historically, these were framed as a mutually exclusive, binary choice inferred largely from canonical genetic lesions such as <em>TERT </em>promoter mutations and <em>ATRX</em>/<em>DAXX</em> loss. Drawing on mechanistic and structural studies of both pathways, large tumor cohorts that co-measure both mechanisms, and quantitative transcriptomic scoring, this review argues that tumor-level telomere maintenance state is better described as a multidimensional, context-dependent property, varying in the magnitude of each mechanism's activity, in the cellular composition of the tumor, and in temporal stability, than as a binary telomerase-versus-ALT label. This review synthesizes the molecular biology of telomere structure, the architecture and regulation of telomerase, and the recombination machinery underlying ALT, and surveys the current state of the art in telomere-directed therapy. Because telomere maintenance is dynamic rather than fixed, tumors capable of switching between or co-engaging maintenance mechanisms may exhibit reduced sensitivity to therapies targeting a single pathway, supporting TMM-stratified therapeutic assessment.</p> Meline Hakobyan Copyright (c) 2026 Meline Hakobyan https://creativecommons.org/licenses/by-nc/4.0 2026-10-26 2026-10-26 126 3 1 1 10.54503/0321-1339-2026.126.3-1