Effect of CXCR9-CXCR3 Cytokine Signaling Pathway in Polycytemia Vera

Abstract

<strong>Objective</strong>: Myeloproliferative neoplasms (MPNs) are among the most common myeloproliferative disorders. MPNs are characterized by excessive production of terminally differentiated blood cells. The expression of CXCR3, responsible for regulating the proliferation of healthy hematopoietic stem cells, is known to be induced by granulocyte-macrophage colony stimulating factor (GM-CSF). The aim of this study is to investigate the role of CXCL9-CXCR3 signaling pathway in the progression of MPN. <strong>Material and Method</strong>: We determined the expression of CXCL9 and two isoforms of the CXCR3 receptor (CXCR3A and CXCR3B) on the surface of human peripheral blood mononuclear cells (PBMC) and cancer stem cells. Real-time polymerase chain reaction (qPCR) was used to measure expression levels, and flow cytometry was used to examine the presence of cell surface receptors. In addition, qPCR was used to quantify CXCR3 expression after GM-CSF application in cell culture. In PBMC and CD34+ cells, the mRNA level of CXCR3A expression was found to be elevated in patients with MPN. <strong>Results</strong>: There was no statistically significant difference in mRNA expression of CXCR3B and CXCL9 between patients and healthy controls.There was significant reduction in cell surface expression of the CXCR3 receptor in PBMC obtained from patients. T <strong>Conclusion</strong>: hus, these results indicate that imbalance in the expression of CXCR3A/CXCR3B isoforms and chemokines CXCL9, CXCL10 and CXCL11 that bind to these receptors, may mediate inflammation and cancer progression in MPN.