Mahmut Bakır KOYUNCU, Hakan BASİR, Mustafa ILGAN, Mehmet Ali UÇAR, Aydan AKDENİZ, Anıl TOMBAK, Eyüp Naci TİFTİK, Salim NEŞELİOĞLU, Özcan EREL

Polisitemi Veralı Hastalarda Dinamik Thiol/Disulfit Dengesi ve İskemi Modifiye Albumin Düzeyleri

Amaç: Polisitemi vera, eritrosit artışı ve JAK2 mutasyonu pozitifliği ile karakterize olan kronik bir miyeloproliferatif hastalıktır. Polisitemi veralı hastalarda miyelofibroz ve akut lösemiye dönüşüm görülebilir. Oksidatif stres, DNA hasarına neden olur ve malign dönüşüme yol açabilir. Tiyol molekülleri, oksidatif stresin zararlı etkilerini önleyebilir. Bu nedenle, bu çalışmada polisitemi veralı hastalarda tiyol homeostazı durumunun analiz edilmesi amaçlandı. Gereç ve Yöntemler: Bu çalışmaya polisitemi veralı 31 hasta ve 80 sağlıklı gönüllü dahil edildi. Vakaların serum örnekleri toplanarak çalışma sonuna kadar saklandı. Doğal tiyol, toplam tiyol, disülfit ve iskemi modifiye albümin seviyeleri belirlendi. Bulgular: Ortalama iskemi modifiye albümin (1,09±0,21'e karşı 0,67±0,08; p<0,001), ortalama disülfit (23,5±6,1'e karşı 10,7±2,6; p<0,001), ortalama disülfit/doğal tiyol oranı (5,6±1,1'e karşı 3,1±1,2; p<0,001), ortalama disülfit/toplam tiyol oranı (5,0±0,9'a karşı 2,9±1,0; p<0,001), ortalama doğal tiyol (418,9±80,6'ya karşı 371,4±103,7; p=0,024), ortalama toplam tiyol (466,0±89,8 393,0±105,5; p=0,001) ve ortalama disülfit/toplam tiyol oranı (89,8±1,8'e karşı 94,1±2,0; p<0,001) polisitemi vera hastalarında daha yüksek idi. İskemi modifiye albümin düzeyleri ayrıca yüksek riskli polisitemi vera hastalarında daha yüksek idi. Ruksolitinib tedavisi alan hastalar daha yüksek doğal tiyol, toplam tiyol ve disülfit seviyeleri ile daha yüksek disülfit/doğal tiyol ve disülfit/toplam tiyol oranlarına sahipti. Sonuç: Tedavi altında olan polisitemi veralı hastalarda oksidatif stres belirteçleri hala yüksektir. Ayrıca, ruxolitinib bu hastalarda oksidatif stresi azaltmak için faydalı olabilir.

Anahtar Kelimeler:

disulfit, polistemi vera, oksidatif stres, tiyol

Dynamic Thiol/Disulfide Balance and Ischemia Modified Albumin Levels in Patients with Polycythemia Vera

Aim: Polycythemia vera is a chronic myeloproliferative disease characterized by increased red cell mass and JAK2 mutation positivity. Transformation to myelofibrosis and acute leukemia is possible in patients with polycythemia vera. Oxidative stress causes DNA damage and might be a reason for malignant transformation. Thiol molecules can prevent the harmful effects of oxidative stress. Therefore, in this study, we aimed to analyze the state of thiol homeostasis in patients with polycythemia vera. Material and Methods: Thirty-one patients with polycythemia vera and 80 healthy volunteers were included in this study. Serum samples of the cases were stored until the end of the study. Native thiol, total thiol, disulfide, and ischemia modified albumin levels were determined. Results: The mean ischemia modified albumin (1.09±0.21 vs 0.67±0.08; p<0.001, mean disulfide (23.5±6.1 vs 10.7±2.6; p<0.001), the mean disulfide/native thiol ratio (5.6±1.1 vs 3.1±1.2; p<0.001), the mean disulfide/total thiol ratio (5.0±0.9 vs 2.9±1.0; p<0.001), the mean native thiol (418.9±80.6 vs 371.4±103.7; p=0.024), the mean total thiol (466.0±89.8 vs 393.0±105.5; p=0.001) and the mean disulfide/total thiol ratio (89.8±1.8 vs 94.1±2.0; p<0.001) were found higher in polycythemia vera patients. Ischemia modified albumin levels were also higher in high-risk polycythemia vera patients. Patients on ruxolitinib therapy had higher native thiol, total thiol and disulfide levels, and higher disulfide/native thiol and disulfide/total thiol ratios. Conclusion: Oxidative stress markers are still high in patients with polycythemia vera who were under treatment. Besides, ruxolitinib may be helpful to decrease oxidative stress in these patients.

Keywords:

disulfide, polycythemia vera, oxidative stress, thiol,

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