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HIGH CXCR3 AND CXCR5 DISTINGUISH IGHVMUT FROM IGHVUNMUT CHRONIC LYMPHOCYTIC LEUKEMIA: EVIDENCE FROM CD5HIGH AND CD5LOW CLONES

PB1884

Gabcova, G.1; Manukyan, G.2; Papajik, T.3; Mikulkova, Z.1; Urbanova, R.3; Kudelka, M.4; Kraiczova, Smotkova V.1; Zehnalova, S.4; Turcsanyi, P.3; Kriegova, E.1

doi: 10.1097/01.HS9.0000566040.99149.16
Publication Only: Chronic lymphocytic leukemia and related disorders - Biology & translational research
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1Department of Immunology, Faculty of Medicine and Dentistry, Palacký University and University Hospital, Olomouc, Czech Republic

2Laboratory of Molecular and Cellular Immunology, Institute of Molecular Biology NAS RA, Yerevan, Armenia

3Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University and University Hospital, Olomouc

4Department of Computer Science, Faculty of Electrical Engineering and Computer Science, VSB-Technical University of Ostrava, Ostrava, Czech Republic

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Background:

Despite the shared pattern of surface antigens, neoplastic cells in chronic lymphocytic leukemia (CLL) demonstrate heterogeneity in their molecular and functional characteristics. Given the dynamic variability of CD5 expression and its link to the proliferative pool of neoplastic cells, more detailed characterization of CLL cell subpopulations are needed.

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Aims:

To further characterize the chemokine receptors (CCR5, CCR7, CCR10, CXCR3, CXCR4, CXCR5) and adhesion molecules (CD54, CD62L, CD49d) on the CD5high and CD5low neoplastic clones in peripheral blood in CLL.

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Methods:

Study cohort consisted of CLL patients (n = 60) subgrouped according to the IgHV mutational status (IgHVmut, n = 24; IgHVunmut, n = 36). Chemokine receptors and adhesion molecules on CD5high and CD5low cell subpopulations, determined by CD5/CD19 co-expression, in peripheral blood were assessed by a six-colour flow cytometry analysis on a BD FACSCanto II (Becton Dickinson). Data were analysed by basic statistics and patient similarity networks.

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Results:

CD5high cell subpopulation expressed high levels of CXCR3 (P < 0.001), CXCR5 (P = 0.005), CCR7 (P = 0.013), CCR10 (P = 0.001), CD62L (P = 0.031) compared to CD5low cells expressing high levels of CXCR4 (P < 0.001). When comparing IgHVmut from IgHVunmut patients, high-levels of CXCR3 and CXCR5 on the whole neoplastic population as well as CD5high and CD5low subpopulations were detected in the IgHVmut patients. Multivariate patient similarity networks confirmed the significance of high CXCR3 levels predominantly on CD5low cells from IgHVmut patients.

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Summary/Conclusion:

Our analysis revealed that CD5high and CD5low neoplastic clones from IgHVmut and IgHVunmut differed mainly by the expression of CXCR3. Further characterization of neoplastic cell heterogeneity and role of CXCR3 will advance our understanding of CLL biology and its clinical relevance.

Grants: MZ ČR VES16-32339A, IGA UP_2019_014, IGA_LF_2019_001, MH CZ-DRO (FNOL, 00098892)

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.