Open AccessPB1884 HIGH CXCR3 AND CXCR5 DISTINGUISH IGHVMUT FROM IGHVUNMUT CHRONIC LYMPHOCYTIC LEUKEMIA: EVIDENCE FROM CD5HIGH AND CD5LOW CLONES
Author(s) -
Gabcova G.,
Manukyan G.,
Papajik T.,
Mikulkova Z.,
Urbanova R.,
Kudelka M.,
Smotkova Kraiczova V.,
Zehnalova S.,
Turcsanyi P.,
Kriegova E.
Publication year - 2019
Publication title -
hemasphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 11
ISSN - 2572-9241
DOI - 10.1097/01.hs9.0000566040.99149.16
Subject(s) - ighv@ , chronic lymphocytic leukemia , cd5 , c c chemokine receptor type 7 , cxcr3 , immunology , cxcr4 , biology , cd19 , c c chemokine receptor type 6 , population , cancer research , antigen , chemokine receptor , microbiology and biotechnology , chemokine , leukemia , medicine , immune system , environmental health
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. Aims: To further characterize the chemokine receptors (CCR5, CCR7, CCR10, CXCR3, CXCR4, CXCR5) and adhesion molecules (CD54, CD62L, CD49d) on the CD5 high and CD5 low neoplastic clones in peripheral blood in CLL. Methods: Study cohort consisted of CLL patients (n = 60) subgrouped according to the IgHV mutational status ( IgHV mut , n = 24; IgHV unmut , n = 36). Chemokine receptors and adhesion molecules on CD5 high and CD5 low 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. Results: CD5 high 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 CD5 low cells expressing high levels of CXCR4 ( P < 0.001). When comparing IgHV mut from IgHV unmut patients, high‐levels of CXCR3 and CXCR5 on the whole neoplastic population as well as CD5 high and CD5 low subpopulations were detected in the IgHV mut patients. Multivariate patient similarity networks confirmed the significance of high CXCR3 levels predominantly on CD5 low cells from IgHV mut patients. Summary/Conclusion: Our analysis revealed that CD5 high and CD5 low neoplastic clones from IgHV mut and IgHV unmut 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)