Integrating TeloView® with Cytogenetics: Biological Characterization of Genomic Instability in CLL Using 3D Telomere Profiling

Chronic lymphocytic leukemia (CLL) is characterized by recurrent chromosomal abnormalities and variable degrees of genomic instability. Telomere dysfunction contributes to this process, and the three-dimensional (3D) nuclear organization of telomeres reflects structural alterations associated with chromosomal aberrations. The objective of this study was biological characterization rather than prognostication. We investigated how 3D telomere architecture varies across cytogenetic subgroups of CLL, without correlating telomere parameters with clinical outcomes. TeloView® technology was applied to peripheral blood samples from 48 CLL patients to quantify 3D telomere parameters, including telomere number, length (signal intensity), aggregate formation, nuclear volume, and a/c ratio. Cytogenetic abnormalities—del(13q14), trisomy 12, del(11q22), and del(17p13)—were identified using conventional karyotyping following DSP30/IL-2 stimulation and interphase fluorescence in situ hybridization. Telomere parameters were compared across cytogenetic subgroups to assess their association with genomic instability. Distinct differences in 3D telomere architecture were observed among cytogenetic categories. High-risk abnormalities, including del(17p13) and del(11q22), were associated with increased telomere aggregates, higher signal intensity clusters, and larger nuclear volumes, whereas cases with isolated del(13q14) displayed more preserved telomere profiles. Trisomy 12 exhibited an intermediate telomeric pattern. In conclusion, 3D telomere organization parallels the biological gradient of cytogenetic complexity in CLL, supporting a mechanistic association between telomere structural disruption and genomic instability.