Analysis of the Cytogenomic and Telomeric Profile in Chronic Lymphocytic Leukemia: Impact Prognostic
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Chronic Lymphocytic Leukemia (CLL) is a malignant neoplasm characterized by the abnormal accumulation of mature B lymphocytes. Genomic instability, a fundamental feature of CLL, drives the occurrence of cytogenomic alterations that define distinct prognostic subgroups. In addition to these alterations, telomere dysfunction, structures that maintain genomic integrity, is associated with greater genetic complexity and a poorer prognosis. Thus, the integrated evaluation of cytogenomic and telomeric profiles broadens the understanding of CLL biology and may contribute for the better disease prognostic stratification. Aim To analyze the cytogenomic and telomeric profile in CLL and their impact on prognosis. Methods A retrospective cross-sectional study (2016-2026) was conducted using peripheral blood samples from CLL patients at the Hematology Service at National Cancer Institute. Cytogenomic analysis was performed by Multiplex Ligation-dependent Probe Amplification (MLPA) using the P037 CLL-1 and P038 CLL-2 kits. Cytogenetic alterations, del(13q), del(11q), and del(17p) were confirmed by Fluorescence in situ hybridization technique. Relative telomere length (RTL) was measured by quantitative PCR. Statistical analyses were performed using GraphPad Prism 8.0.2 software. Results MLPA analysis was performed in 39 cases (26 men and 13 women; mean age of 68.4 years), and alterations were detected in 69.2% of cases. The most frequent alterations were: del(13q) (40.7%), del(11q) (25.9%), trisomy 12 (+12) (25.9%), del(14q) (22.2%), del(17p) (14.8%), and NOTCH1 mutation (11.1%). RTL analysis was performed in 55 samples (36 men and 19 women; mean age of 67 years) and the results were compared with a control group (19 women and 31 men; mean age of 61 years). Patients with CLL showed significantly shorter RTL compared to controls (T/S = 0.81 vs. 1.00; p < 0.001). Analyzing the association between telomere length and cytogenomic and clinical risk factors in patients with CLL, we observed that patients with poor-prognosis harboring del(17p) and NOTCH1 mutations, telomere lengthening was higher compared to the other CLL cytogenetic subgroups (p = 0.01). The group with unmutated IGHV also exhibited telomere elongation compared to the group with mutated IGHV (p = 0.001). Furthermore, treated CLL patients exhibited longer telomeres than the untreated group (p = 0.0005). Discussion: Patients with CLL generally exhibit shorter telomeres, reflecting the disease's typical replicative exhaustion. However, telomere lengthening in high-risk subgroups harboring del(17p), NOTCH1 mutations, and unmutated IGHV, suggests a mechanism of escape from senescence and the telomere maintenance. This adaptive advantage allows for the selection of clones that achieve replicative immortality, driving intense proliferation and clonal aggressiveness within settings of high genomic instability. Conclusion Our results suggest that, in poor-prognosis CLL subgroups characterized by high genomic instability, telomere maintenance mechanisms may drive aggressiveness by conferring replicative immortality and chemotherapy resistance through telomere stabilization and the maintenance of more aggressive clones. The integrated analysis of cytogenomic and telomeric profiles serves as a valuable tool for understanding CLL biology and identifying patients at higher risk of disease progression.
Institution: Instituto Nacional de Câncer - INCA
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223135976