Thiol/disulfide balance in patients with newly diagnosed chronic myeloid leukemia and its relationship with Sokal prognostic score

Year 2022, Volume: 15 Issue: 1, 1 - 7, 30.04.2022

Mahmut Bakır Koyuncu , Anıl Tombak , Tolga Köşeci , Ali Turker Hakan Basir , Mustafa İlğan , Aydan Akdeniz , Eyüp Naci Tiftik , Özcan Erel

https://doi.org/10.26559/mersinsbd.951589

Abstract

Aim: Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the presence of the bcr-abl fusion gene. Oxidative stress may play a role in the pathogenesis of this disease by causing DNA damage. Thiol molecules protect the organism from the harmful effects of oxidative stress. In this study, we aimed to investigate the thiol/disulfide balance in CML patients. Method: A total of 48 patients with CML and 80 healthy individuals were included in the study. The collected venous blood samples were centrifuged and the serum part was stored at -80 0C until all samples were studied. Native thiol, total thiol, disulfide and ischemia modified albumin (IMA) levels were studied from these blood samples. Results: The median Sokal score of the patients was calculated as 0.78 (0.56-1.37). In the Sokal score categories, a significant difference was found between the levels of native thiol, total thiol, disulfide/native thiol, disulfide/total thiol, native thiol/total thiol and IMA. When the patient and control groups were compared in terms of oxidative stress measurement, the measurements in the patients were found to be consistent with increased oxidative stress. Serum IMA levels were found to be significantly higher in patients in the high-risk group according to the Sokal score, and it was observed that IMA levels increased as the risk increased (p<0.001). Conclusion: Oxidative stress parameters are significantly higher in CML patients than in normal individuals. In particular, serum IMA levels are significantly higher in high-risk patients according to Sokal and can be included in future prognostic scores.

Keywords

Chronic myeloid leukemia, oxidative stress, Sokal score

Supporting Institution

none

Yeni tanı kronik myeloid lösemili hastalarda tiyol/disülfit dengesi ve Sokal prognostik skoru ile ilişkisi

Abstract

Amaç: Kronik myeloid lösemi (KML), bcr-abl füzyon geninin pozitifliği ile karakterize olan myeloproliferatif bir hastalıktır. Oksidatif stres bu hastalarda DNA hasarına yol açarak hastalığın patogenezinde rol oynuyor olabilir. Thiol molekülleri organizmayı oksidatif stresin zararlı etkilerinden korumaktadır. Biz de bu çalışmamızda KML hastalarında thiol/disülfit dengesinin durumunu araştırmayı amaçladık. Yöntem: Toplam 48 hasta ve 80 sağlıklı birey çalışmaya dahil edildi. Alınan venöz kan örnekleri santrifüj edilerek ayrılan serum kısmı -800C’de tüm örnekler çalışılana kadar saklandı. Bu kan örneklerinden native thiol, total thiol, disülfit ve İskemi modifiye albümin (İMA) çalışıldı. Bulgular: Hastaların medyan Sokal skoru 0.78 (0.56-1.37) olarak hesaplandı. Sokal skor kategorilerinde native thiol, total thiol, disülfit/native thiol, disülfit/total thiol, native thiol/total thiol ve İMA düzeyleri arasında anlamlı farklılık tespit edilmiştir. Hasta ve kontrol grubu oksidatif stres ölçümü bakımından karşılaştırıldığında, hastalardaki ölçümler artmış oksidatif stres ile uyumlu bulunmuştur. Sokal skoruna göre yüksek risk grubunda yer alan hastalarda serum İMA düzeylerinin anlamlı derecede daha yüksek olduğu görülmüş ve risk arttıkça İMA düzeylerinde de anlamlı düzeyde artış olduğu görülmüştür (p<0.001). Sonuç: KML hastalarında oksidatif stres parametreleri normal bireylere göre anlamlı derecede daha yüksektir. Özellikle serum İMA düzeyleri, Sokal’a göre yüksek risk hastalarda belirgin yüksek olup gelecekte yeni geliştirilecek prognostik skorlara dahil edilebilir.

Keywords

Kronik myeloid lösemi, oksidatif stres, Sokal skoru

References

• Van Etten RA. c-Abl regulation: a tail of two lipids. Curr Biol. 2003;13(15):R608-610.
• Aijaz J, Junaid N, Asif Naveed M, Maab R. Risk Stratification of Chronic Myeloid Leukemia According to Different Prognostic Scores. Cureus. 2020;12(3):e7342.
• Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in "good-risk" chronic granulocytic leukemia. Blood. 1984;63(4):789-799.
• Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol. 2009;7(1):65-74.
• Ali UM, Tombak A, Dagdas S, et al. Is dynamic thiol/disulfide homeostasis associated with the prognosis of myelodysplastic syndrome? J Med Biochem. 2020;39(3):336-345.
• Kundi H, Ates I, Kiziltunc E, et al. A novel oxidative stress marker in acute myocardial infarction; thiol/disulphide homeostasis. Am J Emerg Med. 2015;33(11):1567-1571.
• Dirican N, Dirican A, Sen O, et al. Thiol/disulfide homeostasis: A prognostic biomarker for patients with advanced non-small cell lung cancer? Redox Rep. 2016;21(5):197-203.
• Gulpamuk B, Tekin K, Sonmez K, et al. The significance of thiol/disulfide homeostasis and ischemia-modified albumin levels to assess the oxidative stress in patients with different stages of diabetes mellitus. Scand J Clin Lab Invest. 2018;78(1-2):136-142.
• Karaşin SS, Çift T. The Role of Ischemia-modified Albumin as a Biomarker in Preeclampsia. Rev Bras Ginecol Obstet. 2020;42(3):133-139.
• Sahin A, Turkoglu S, Tunc N, et al. Is ischemia-modified albumin a reliable tool for the assessment of acute pancreatitis? Ther Clin Risk Manag. 2018;14:627-635.
• Ahmad R, Tripathi AK, Tripathi P, Singh R, Singh S, Singh RK. Oxidative stress and antioxidant status in patients with chronic myeloid leukemia. Indian J Clin Biochem. 2008;23(4):328-333.
• Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem. 2014;47(18):326-332.
• Allegra A, Pioggia G, Tonacci A, Casciaro M, Musolino C, Gangemi S. Synergic Crosstalk between Inflammation, Oxidative Stress, and Genomic Alterations in BCR-ABL-Negative Myeloproliferative Neoplasm. Antioxidants (Basel). 2020;9(11).
• Rossi C, Zini R, Rontauroli S, et al. Role of TGF-β1/miR-382-5p/SOD2 axis in the induction of oxidative stress in CD34+ cells from primary myelofibrosis. Mol Oncol. 2018;12(12):2102-2123.
• Pascu VÎnturiȘ EG, GĂman AM. Assessment of Oxidative Stress in Patients with Chronic Myeloid Leukemia Depending on Associated Comorbidities. Curr Health Sci J. 2020;46(1):23-30.
• Pilo F, Angelucci E. A storm in the niche: Iron, oxidative stress and haemopoiesis. Blood Rev. 2018;32(1):29-35.
• Winterbourn CC. Are free radicals involved in thiol-based redox signaling? Free Radic Biol Med. 2015;80:164-170.
• Poole LB. The basics of thiols and cysteines in redox biology and chemistry. Free Radic Biol Med. 2015;80:148-157.
• Ellidag HY, Aydin O, Eren E, Yilmaz N, Ergin M. Decreased HDL-dependent paraoxonase and arylesterase enzyme activity may indicate a worse prognosis in multiple myeloma. Asian Pac J Cancer Prev. 2014;15(22):9847-9851.
• Gündüztepe Y, Bukan N, Zorlu E, et al. The evaluation of thiol-disulfıte balance, ischemıa albumın modıfıcation and seruloplazmine as a new oxidatıve stress in mild cognitive impairment and early stage alzheimer's disease patients. J Clin Neurosci. 2020;75:188-194.
• Oran I, Oran B. Ischemia-Modified Albumin as a Marker of Acute Coronary Syndrome: The Case for Revising the Concept of "N-Terminal Modification" to "Fatty Acid Occupation" of Albumin. Dis Markers. 2017;2017:5692583.