Effect of CXCL9-CXCR3 Cytokine Signaling Pathway in Polycytemia Vera

Year 2018, Volume: 8 Issue: 3, 84 - 92, 02.12.2018

Cemil Altunay Akif Selim Yavuz Selçuk Sözer Tokdemir

Abstract

DOI:
10.26650/experimed.2019.18006

Objective: 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.

Keywords

Myeloproliferative disorders, JAK2V617F, CXCL9- CXCR3

Polisitemia Vera’da CXCL9-CXCR3 Sitokin Sinyal Yolağının Etkisi

Abstract

DOI:
10.26650/experimed.2019.18006

Amaç: 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.

Keywords

Myeloproliferatif neoplaziler, JAK2V617F, CXCR9- CXCL3

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