High CXCR3 on Leukemic Cells Distinguishes IgHVmut from IgHVunmut in Chronic Lymphocytic Leukemia: Evidence from CD5high and CD5low Clones. (20th June 2020)

• Record Type: Journal Article
• Authors: Manukyan, Gayane; Papajik, Tomas; Mikulkova, Zuzana; Urbanova, Renata; Kraiczova, Veronika Smotkova; Savara, Jakub; Kudelka, Milos; Turcsanyi, Peter; Kriegova, Eva
• Other Names: Bagatini Margarete D. Guest Editor.
• Is Part Of: Journal of immunology research. Volume 2020(2020)
• Publication Date: 2020-06-20
• Subjects: Immunology -- Periodicals; Immunology -- Research -- Periodicals; 616.07905
• DOI: 10.1155/2020/7084268
• Languages: English
• ISSNs: 2314-8861

Abstract

Abstract : 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 CD5 high and CD5 low neoplastic cells, we assessed the chemokine receptors (CCR5, CCR7, CCR10, CXCR3, CXCR4, CXCR5) and adhesion molecules (CD54, CD62L, CD49d) on the CD5 high and CD5 low subpopulations, defined by CD5/CD19 coexpression, in peripheral blood of CLL patients (n = 60 ) subgrouped according to the IgHV mutational status ( IgHV mut, n = 24 ; IgHV unmut, n = 36 ). CD5 high 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 CD5 low cells expressing high CXCR4 (P < 0.001 ). Comparing IgHV mut and IgHV unmut patients, high levels of CXCR3 on CD5 high and CD5 low subpopulations were detected in the IgHV mut patients, with better discrimination in CD5 low subpopulation. Levels of CXCR3 on CD5 low 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 CD5 high and CD5 low neoplastic cells in IgHV mut with a better prognosis compared to IgHV unmut patients. Contribution of CXCR3 to CLL pathophysiology and its suitability for prognostication and therapeutic exploitation deserves future investigations.