Project objective and scope
The main objective of the project is to develop a diagnostic and prognostic panel based on the analysis of nucleic acid modifications for the early diagnosis, prognosis determination, and treatment monitoring of chronic lymphocytic leukemia (CLL).
What is CLL and why do we need new diagnostic tools?
Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in Western countries. In clinical practice, diagnosis is based on blood morphology and immunophenotyping by flow cytometry. The quantitative criterion for diagnosis is the presence of ≥ 5 × 10⁹/L (≥ 5000/µl) of clonal B lymphocytes with a typical CLL immunophenotype in peripheral blood. At the same time, there are borderline conditions and related entities (e.g., monoclonal B-cell lymphocytosis – MBL; small lymphocytic lymphoma – SLL), which can be difficult to distinguish in some cases and require further diagnosis.
Despite advances in treatment, the following remain significant challenges: (1) early differential diagnosis, (2) accurate determination of prognosis and risk of progression, and (3) objective monitoring of response to therapy. A particularly important direction is the development of approaches to support the assessment of minimal residual disease (MRD), which has a documented prognostic significance in CLL and is increasingly becoming a benchmark in clinical trials of new therapies.
Specific objectives
Selection of biomarkers with the greatest diagnostic and prognostic potential in CLL based on current knowledge and additional analysis of archival material.
Adaptation of analytical techniques (UPLC-MS/MS and flow cytometry) for use in routine diagnostic laboratories, taking into account regulatory requirements (in particular IVDR) and maximum process automation.
Development of optimal calibration and control procedures and validation of pre-analytical stages (collection, transport, storage, preparation of material).
Testing of the developed solutions on a laboratory scale and preparation of an implementation path.
Conducting information and promotional activities to disseminate the results of the project.
Why nucleic acid modifications?
Modifications of bases in DNA and RNA are an integral part of gene expression regulation and genome stability. Through many years of research, the project team has identified DNA modifications associated with active demethylation and deamination pathways that clearly differentiate CLL patients from individuals without hematopoietic hyperplasia and can predict the time to treatment initiation. The project develops this concept towards a solution that can be routinely used in diagnostics.