P121 | a Valid Predictive Approach in Patients With Chronic Lymphocytic Leukemia: Combination of Multigene Profiling and High-sensitivity Minimal Residual Disease Assessment
Year: 2025
Type: article
Abstract: The correlation between the genetic heterogeneity of CLL and clinical diversity still remains unclear, although Next Generation Sequencing (NGS) approaches have contributed to the improvement of such knowledge. The presented study suggests that wide genetic profiling of patients in pre-treatment onset or suspected relapse/progression is needed, with the aim of perfecting the prognostic stratification. The recruited cohort consists of 30 patients diagnosed with CLL, characterised at a genetic-molecular level, through more extensive NGS analyses than required by current guidelines. The evaluation of the mutational status of the IGH gene revealed 17 non-mutated, 9 mutated, 3 inconclusive and 1 polyclonal. The mutational profile of the patients, defined using a custom multigene panel including 23 genes associated with the main lymphoproliferative disorders, identified 26 positive cases with at least one variant. Overall, 67 somatic variants were identified and classified: 25 as Tier I, 26 as Tier II and 16 as Tier III. The most frequently mutated genes are NOTCH1, TP53, KRAS, POT1, XPO1, BRAF and FBXW7. MRD evaluation by NGS was performed for 7 patients undergoing specific therapeutic protocols, detecting 2 negative (sensitivity 10-4) and the remaining positive. The integration of the study of IGH mutational status and a more comprehensive genetic profile may improve prognostic stratification, contributing to the resolution of weakly defined cases such as subjects with inconclusive/borderline or TP53 negative IGH mutational status. The mutational genetic profile is also confirmed to be a predictor of patients' clinical course, if compared to MRD evaluation. Indeed, post treatment MRD positive cases present a molecular profile that can be defined as high risk, compatible with clinical outcome. To conclude, NGS analysis appears to be a valid approach in prognostic stratification and prediction of treatment efficacy for these patients, although further investigation is required.
Authors: E. Borotti, E. Ronda, A. Scarpa, V. Scaglia, A. Arcari, L. Morello, A. Rossi, D. Vallisa
Institution: Azienda Unità Sanitaria Locale Piacenza
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093122331
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