Polisitemia Vera’da CXCL9-CXCR3 Sitokin Sinyal Yolağının Etkisi

DOI: 10.26650/experimed.2019.18006Amaç: Miyeloproliferatif Neoplaziler (MPN), miyeloproliferatif bozukluklar arasında en sık görülen hastalıklardandır. Tamamen işlevsel olan ve son aşamaya kadar farklılaşmış kan hücrelerinin aşırı üretimi ile karakterize edilirler. Önceki çalışmalarda Granülosit-Makrofaj Koloni Uyarıcı Faktörün (GM-CSF) sağlıklı hematopoietik kök hücreler (HKH)’de proliferasyon kontrolünden sorumlu CXCR3 ekspresyonunu arttırdığı gösterilmiştir. Bu çalışmanın amacı, CXCL9-CXCR3 sinyal yolağının MPN progresyonunda etkisinin araştırılmasıdır. Gereç ve Yöntem: Çalışmada, MPN ve sağlıklı  insan perifer kan mononükleer hücrelerinde (MNH) ve kanser HKH de CXCL9 kemokini ve bunun reseptörü olan CXCR3’ün iki izoformunun (CXCR3A ve CXCR3B) gen ifade seviyeleri, MNH yüzeyinde ise CXCR3 reseptör varlığı incelenmiştir. Ekspresyon seviyelerini araştırmak amacıyla kantitatif gerçek zamanlı polimeraz zincir reaksiyonu (PZR), hücre yüzey reseptör durumunun incelenmesi içinse akım ölçer metotları kullanılmıştır. GM-CSF’in MNH ve CD34+ hücrelerinde uygulamasının ardından CXCR3 ekspresyonu değerlendirilmiştir. Bulgular: MNH’de CXCR3A ifadesinin hastalarda sağlıklılara göre istatistiksel olarak anlamlı arttığı bulunmuşur. Hasta ve sağlıklı kontrol grupları arasında CXCR3B ve CXCL9 ifade seviyeleri kıyaslandığında istatistiksel olarak anlamlı bir fark olmadığı tespit edilmiştir. CXCR3 Hücre yüzey reseptör durumuna bakıldığında ise hastalardan elde edilen MNH’deki anlatımda sağlıklı gruptan elde edilenlere göre anlamlı bir azalma olduğu görülmüştür. Sonuç: Bu sonuçlar MPN’de CXCR3A/CXCR3B dengesi ile bu reseptörlere özgün olarak bağlanan kemokinler CXCL9, CXCL10 ve CXCL11’in inflamasyon ve kanser progresyonu ile ilişkili olabileceğini düşündürmektedir.

Effect of CXCL9-CXCR3 Cytokine Signaling Pathway in Polycytemia Vera

DOI: 10.26650/experimed.2019.18006Objective: 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. Material and Method: 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. Results: 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 Conclusion: 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.

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