Turk J Hematol. 2019; 36(3): 178-185 | DOI: 10.4274/tjh.galenos.2019.2018.0420

The Role of the Local Bone Marrow Renin-Angiotensin System in Multiple Myeloma

Bülent Saka¹, Müge Sayitoğlu², Zülal İstemihan¹, Mehmet Akif Karan¹, Sebile Nilgün Erten¹, Öner Doğan³, Uğur Özbek², Sema Genç⁴, Cemil Taşçıoğlu¹, Sevgi Kalayoğlu Beşışık^1
1İstanbul University, İstanbul Faculty of Medicine, Department of Internal Medicine, İstanbul, Turkey
²İstanbul University, Aziz Sancar Institute of Experimental Research, Department of Genetics, İstanbul, Turkey
³İstanbul University, İstanbul Faculty of Medicine, Department of Pathology, İstanbul, Turkey
⁴İstanbul University, İstanbul Faculty of Medicine, Department of Biochemistry, İstanbul, Turkey

Objective: Angiotensin II promotes growth and angiogenesis via type 1 receptors (AGTR1) in certain tumors. In this study, we examine the bone marrow AGTR1 expression in multiple myeloma (MM) and its relationship with the regulation of angiogenesis and prognostic factors.
Materials and Methods: Bone marrow AGTR1 mRNA levels of 39 MM patients and 15 healthy controls were analyzed with quantitative RT-PCR. Immunohistochemical staining of the tissue vascular endothelial growth factor (VEGF), CD34, and factor VIIIrAg (fVIIIrAg) was used to assess bone marrow angiogenesis.
Results: Bone marrow samples of the patients showed increased VEGF, fVIIIrAg, and CD34 staining and higher AGTR1 expression levels when compared to controls. Patients with severe-diffuse bone marrow infiltration showed higher bone marrow VEGF, fVIIIrAg, CD34, and AGTR1 mRNA levels when compared to other patients.
Conclusion: AGTR1 expression was found positively correlated with plasma β2-microglobulin level and patients with increased AGTR1 expression showed increased bone marrow CD34 levels.

Keywords: Multiple myeloma, Renin-angiotensin system, Angiotensin type 1a receptor

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Multipl Myelomda Lokal Kemik İliği Renin-Anjiyotensin Sisteminin Rolü

Bülent Saka¹, Müge Sayitoğlu², Zülal İstemihan¹, Mehmet Akif Karan¹, Sebile Nilgün Erten¹, Öner Doğan³, Uğur Özbek², Sema Genç⁴, Cemil Taşçıoğlu¹, Sevgi Kalayoğlu Beşışık^1
1İstanbul University, İstanbul Faculty of Medicine, Department of Internal Medicine, İstanbul, Turkey
²İstanbul University, Aziz Sancar Institute of Experimental Research, Department of Genetics, İstanbul, Turkey
³İstanbul University, İstanbul Faculty of Medicine, Department of Pathology, İstanbul, Turkey
⁴İstanbul University, İstanbul Faculty of Medicine, Department of Biochemistry, İstanbul, Turkey

Amaç: Anjiyotensin II, bazı tümörlerde tip 1 reseptörleri (AGTR1) yoluyla bir büyüme promotörü veya anjiyojenik faktör olarak görev yapar. Bu çalışmada, multipl myelomda (MM) kemik iliği AGTR1 ekspresyonunu ve bunun anjiyogenez ve prognostik faktörlerin düzenlenmesi ile ilişkisini incelemekteyiz.
Gereç ve Yöntem: Otuz dokuz MM hastası ve 15 sağlıklı kontrolde, kemik iliği AGTR1 mRNA düzeyleri kantitatif RT-PCR ile analiz edildi. Kemik iliği anjiogenezi, doku vasküler endotel büyüme faktörü (VEGF), CD34 ve faktör VIIIrAg’nın (fVIIIrAg) immünohistokimyasal ölçümü ile değerlendirildi.
Bulgular: Hastalar kontrollerle karşılaştırıldığında daha yüksek kemik iliği VEGF, fVIIIrAg, CD34 ve AGTR1 ekspresyon seviyelerine sahipti ve şiddetli yaygın kemik iliği infiltrasyonu olan hastalar diğer hastalara göre daha yüksek kemik iliği VEGF, fVIIIrAg, CD34 ve AGTR1 mRNA seviyeleri gösterdi.
Sonuç: AGTR1 ekspresyonu, plazma β2-mikroglobulin seviyesi ile korele bulundu ve artan AGTR1 ekspresyonu olan hastalarda kemik iliği CD34 seviyelerinde artış görüldü.

Anahtar Kelimeler: Multipl myelom, Renin-anjiyotensin sistemi, Anjiyotensin tip 1a reseptörü

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