High CXCR3 on Leukemic Cells Distinguishes IgHVmut from IgHVunmut in Chronic Lymphocytic Leukemia: Evidence from CD5high and CD5low Clones

Despite the shared pattern of surface antigens, neoplastic cells in chronic lymphocytic leukemia (CLL) are highly heterogeneous in CD5 expression, a marker linked to a proliferative pool of neoplastic cells. To further characterize CD5high and CD5low neoplastic cells, we assessed the chemokine recep...

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Main Authors: Gayane Manukyan, Tomas Papajik, Zuzana Mikulkova, Renata Urbanova, Veronika Smotkova Kraiczova, Jakub Savara, Milos Kudelka, Peter Turcsanyi, Eva Kriegova
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2020/7084268
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author Gayane Manukyan
Tomas Papajik
Zuzana Mikulkova
Renata Urbanova
Veronika Smotkova Kraiczova
Jakub Savara
Milos Kudelka
Peter Turcsanyi
Eva Kriegova
author_facet Gayane Manukyan
Tomas Papajik
Zuzana Mikulkova
Renata Urbanova
Veronika Smotkova Kraiczova
Jakub Savara
Milos Kudelka
Peter Turcsanyi
Eva Kriegova
author_sort Gayane Manukyan
collection DOAJ
description Despite the shared pattern of surface antigens, neoplastic cells in chronic lymphocytic leukemia (CLL) are highly heterogeneous in CD5 expression, a marker linked to a proliferative pool of neoplastic cells. To further characterize CD5high and CD5low neoplastic cells, we assessed the chemokine receptors (CCR5, CCR7, CCR10, CXCR3, CXCR4, CXCR5) and adhesion molecules (CD54, CD62L, CD49d) on the CD5high and CD5low subpopulations, defined by CD5/CD19 coexpression, in peripheral blood of CLL patients (n=60) subgrouped according to the IgHV mutational status (IgHVmut, n=24; IgHVunmut, n=36). CD5high subpopulation showed a high percentage of CXCR3 (P<0.001), CCR10 (P=0.001), and CD62L (P=0.031) and high levels of CXCR5 (P=0.005), CCR7 (P=0.013) compared to CD5low cells expressing high CXCR4 (P<0.001). Comparing IgHVmut and IgHVunmut patients, high levels of CXCR3 on CD5high and CD5low subpopulations were detected in the IgHVmut patients, with better discrimination in CD5low subpopulation. Levels of CXCR3 on CD5low subpopulation were associated with time to the next treatment, thus further confirming its prognostic value. Taken together, our analysis revealed higher CXCR3 expression on both CD5high and CD5low neoplastic cells in IgHVmut with a better prognosis compared to IgHVunmut patients. Contribution of CXCR3 to CLL pathophysiology and its suitability for prognostication and therapeutic exploitation deserves future investigations.
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institution Kabale University
issn 2314-8861
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spelling doaj-art-37eb7bf4416c48a69a1de4a8a140e4152025-02-03T06:45:48ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/70842687084268High CXCR3 on Leukemic Cells Distinguishes IgHVmut from IgHVunmut in Chronic Lymphocytic Leukemia: Evidence from CD5high and CD5low ClonesGayane Manukyan0Tomas Papajik1Zuzana Mikulkova2Renata Urbanova3Veronika Smotkova Kraiczova4Jakub Savara5Milos Kudelka6Peter Turcsanyi7Eva Kriegova8Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital, Olomouc, Czech RepublicDepartment of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University and University Hospital, Olomouc, Czech RepublicDepartment of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital, Olomouc, Czech RepublicDepartment of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University and University Hospital, Olomouc, Czech RepublicDepartment of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital, Olomouc, Czech RepublicDepartment of Computer Science, Faculty of Electrical Engineering and Computer Science, VSB-Technical University of Ostrava, Czech RepublicDepartment of Computer Science, Faculty of Electrical Engineering and Computer Science, VSB-Technical University of Ostrava, Czech RepublicDepartment of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University and University Hospital, Olomouc, Czech RepublicDepartment of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital, Olomouc, Czech RepublicDespite the shared pattern of surface antigens, neoplastic cells in chronic lymphocytic leukemia (CLL) are highly heterogeneous in CD5 expression, a marker linked to a proliferative pool of neoplastic cells. To further characterize CD5high and CD5low neoplastic cells, we assessed the chemokine receptors (CCR5, CCR7, CCR10, CXCR3, CXCR4, CXCR5) and adhesion molecules (CD54, CD62L, CD49d) on the CD5high and CD5low subpopulations, defined by CD5/CD19 coexpression, in peripheral blood of CLL patients (n=60) subgrouped according to the IgHV mutational status (IgHVmut, n=24; IgHVunmut, n=36). CD5high subpopulation showed a high percentage of CXCR3 (P<0.001), CCR10 (P=0.001), and CD62L (P=0.031) and high levels of CXCR5 (P=0.005), CCR7 (P=0.013) compared to CD5low cells expressing high CXCR4 (P<0.001). Comparing IgHVmut and IgHVunmut patients, high levels of CXCR3 on CD5high and CD5low subpopulations were detected in the IgHVmut patients, with better discrimination in CD5low subpopulation. Levels of CXCR3 on CD5low subpopulation were associated with time to the next treatment, thus further confirming its prognostic value. Taken together, our analysis revealed higher CXCR3 expression on both CD5high and CD5low neoplastic cells in IgHVmut with a better prognosis compared to IgHVunmut patients. Contribution of CXCR3 to CLL pathophysiology and its suitability for prognostication and therapeutic exploitation deserves future investigations.http://dx.doi.org/10.1155/2020/7084268
spellingShingle Gayane Manukyan
Tomas Papajik
Zuzana Mikulkova
Renata Urbanova
Veronika Smotkova Kraiczova
Jakub Savara
Milos Kudelka
Peter Turcsanyi
Eva Kriegova
High CXCR3 on Leukemic Cells Distinguishes IgHVmut from IgHVunmut in Chronic Lymphocytic Leukemia: Evidence from CD5high and CD5low Clones
Journal of Immunology Research
title High CXCR3 on Leukemic Cells Distinguishes IgHVmut from IgHVunmut in Chronic Lymphocytic Leukemia: Evidence from CD5high and CD5low Clones
title_full High CXCR3 on Leukemic Cells Distinguishes IgHVmut from IgHVunmut in Chronic Lymphocytic Leukemia: Evidence from CD5high and CD5low Clones
title_fullStr High CXCR3 on Leukemic Cells Distinguishes IgHVmut from IgHVunmut in Chronic Lymphocytic Leukemia: Evidence from CD5high and CD5low Clones
title_full_unstemmed High CXCR3 on Leukemic Cells Distinguishes IgHVmut from IgHVunmut in Chronic Lymphocytic Leukemia: Evidence from CD5high and CD5low Clones
title_short High CXCR3 on Leukemic Cells Distinguishes IgHVmut from IgHVunmut in Chronic Lymphocytic Leukemia: Evidence from CD5high and CD5low Clones
title_sort high cxcr3 on leukemic cells distinguishes ighvmut from ighvunmut in chronic lymphocytic leukemia evidence from cd5high and cd5low clones
url http://dx.doi.org/10.1155/2020/7084268
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