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Investigation of the chemokine receptors CCR1 and CCR2 and EBV infection aimed on disclosure of new markers that can predict the high risk for progression of chronic lymphocytic leukemia

Project/agreement No.
lzp-2018/1-0156
Project funding
300 000.00 EUR
Project manager
Project realization
31.08.2018. - 31.08.2021.

Aim

The aim of the project is to validate the CCR1/CCR2 cell-surface expression, as a reliable predictor of high-risk progression in CLL patients at presentation and to evaluate it association with known prognostic factors: progression-free-survival duration/time-to-first treatment, lymphocytes doubling time, IGHV mutational status, CD38- and CD25-positivity of lymphocyte subpopulations, ZAP-70 mRNA expression level, and EBV DNA load.

The project research is focused on disclosure of new biomarkers for personalized early diagnosis of chronic lymphocytic leukemia and the individualized selection of effective treatment that allow significantly reduce and even avoid for years the therapy- and disease-related complications.

Description

Chronic lymphocytic leukemia (CLL), the most common form of leukemia in adults, can be divided into two main types: indolent slowly-progressing (low-risk) and aggressive rapidly-progressing (high-risk) disease. Patients with indolent CLL are not recommended for therapy unless they have evidence for disease progression. The application of the chemotherapy for patients with low-risk CLL forces the switch of the indolent type into an aggressive rapidly-progressing disease and may cause the CLL transformation into more aggressive secondary cancers, and that significantly reduce the overall survival.

Project partner

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Known prognostic factors that can predict the high risk for CLL progression do not identify all cases at risk or are laborious in performing in a routine laboratory diagnostic.

The present project is based on our previous results and aimed on validation of new putative prognostic markers, the cell-surface chemokine receptors CCR1 and CCR2. The project includes the retrospective study of 90 CLL patients, 60 at the diagnosis and 30 relapsed after the treatment, and the study of newly included patients diagnosed with CLL.

CLL is characterized by extremely variable clinical manifestation ranges from patients, who do not require therapy for many years and may never need any treatment, to others, with the aggressive form of the disease, who survive no more than 3 years after the diagnosis. The introduction of the reliable markers that can predict the high risk for progression in CLL patients at the presentation, into routine diagnostic procedure (the immunophenotypic identification using flow cytometry) will allow to assess the prognosis and to select the curative treatments for most CLL patients.