Background: This study planned to investigate the relationship of dynamic thiol/disulfide homeostasis with the prognosis of myelodysplastic syndrome (MDS).
Methods: 80 patients who had been diagnosed with MDS between 2012 and 2017 and who were older than 18 were included in the study together with 80 healthy control subjects. The MDS diagnosis was confirmed using bone marrow aspiration-biopsy immunostaining. Dynamic thiol/disulfide homeostasis and ischemia-modified albumin (IMA) levels were examined.
Results: The average IMA (0.71±0.08 vs. 0.67±0.09; p=0.002), median disulfide (18.0 vs. 11.6; p<0.001), median disulfide/native thiol (6 vs. 3; p<0.001), and median disulfide/total thiol (5.4 vs. 2.9; p<0.001) were found higher in the MDS patients compared to control group, and the median hemoglobin, median white blood cell count, median neutrophil count, median lymphocyte count, average native thiol (290.7±48.5 vs. 371.5±103.8; p<0.001), average total thiol (328.2±48.9 vs. 393±105.5; p<0.001), and average native thiol/total thiol (%) (88.3±4.3 vs. 94.2±2.1; p<0.001) were found to below. Risk factors such as collagen tissue disease (HR:9.17; p=0.005), MDS-EB-1 (HR:10.14; p=0.032), MDS-EB-2 (HR:18.2; p=0.043), and disulfide/native thiol (HR:1.17; p=0.023) were found as the independent predictors anticipating progression to acute myeloid leukemia. In the Cox regression model, risk factors such as age (HR:1.05; p=0.002), MDS-EB-1 (HR:12.58; p<0.001), MDS-EB-2 (HR:5.75; p=0.033), disulfide/native thiol (HR:1.14; p=0.040), and hemoglobin (HR:0.64; p=0.007) were found as predictors anticipating for mortality.
Conclusions: We can argue that dynamic thiol/disulfide homeostasis could have significant effects on both the etiopathogenesis and the survival of patients with MDS, and it could be included in new prognostic scoring systems.
Uvod: Plan ove studije je bio da istraži vezu dinamične tiol/disulfidne homeostaze i prognoze mijelodisplastičnog sindroma (MDS).
Metode: U istraživanje je uključeno 80 pacijenata kojima je dijagnostifikovan MDS između 2012. i 2017, starijih od 18 godina, i 80 zdravih kontrolnih ispitanika. MDS dijagnoza je potvrđena imunološkim bojenjem koštane srži dobijene aspiracionom biopsijom. Ispitani su dinamična tiol/disulfidna homeostaza i nivoi albumina modifikovanog ishemijom (IMA).
Rezultati: Otkriveno je da su vrednosti prosečnog IMA (0,71 ± 0,08 nasuprot 0,67 ± 0,09; p = 0,002), vrednost medijane disulfida (18,0 naspram 11,6; p < 0,001) i disulfid/nativniog tiola (6 naspram 3; p < 0,001) i medijane disulfid/ukupnog tiola (5,4 naspram 2,9; p < 0,001) veće kod bolesnika sa MDS-om u poređenju sa kontrolnom grupom. Takođe, otkrivene su i niske vrednosti medijane hemoglobina, belih krvnih zrnaca, neutrofila, limfocita, prosečnog nativnog tiola (290,7 ± 48,5 naspram 371,5 ± 103,8; p < 0,001), prosečnog ukupnog tiola (328,2 ± 48,9 u odnosu na 393 ± 105,5; p <0,001) i prosečnog nativnog tiola/ukupni tiol (%) (88,3 ± 4,3 prema 94,2 ± 2,1; p < 0,001). Faktori rizika poput bolesti kolagenskih tkiva (HR: 9,17; p = 0,005), MDS-EB-1 (HR: 10,14; p = 0,032), MDS-EB-2 (HR: 18,2; p = 0,043), i disulfid/nativni tiol (HR: 1,17; p = 0,023) su otkriveni kao nezavisni prediktori koji predviđaju napredovanje do akutne mijeloidne leukemije. Po Koksovom modelu regresije, faktori rizika kao što su starost (HR: 1,05; p = 0,002), MDS-EB-1 (HR: 12,58; p <0,001), MDS-EB-2 (HR: 5,75; p = 0,033), disulfid/nativni tiol (HR: 1,14; p = 0,040) i hemoglobin (HR: 0,64; p = 0,007) smatraju se prediktorima smrtnosti.
Zaključak: Možemo tvrditi da bi dinamička tiol-disulfidna homeostaza mogla da ima značajne efekte i na etiopatogenezu i na preživljavanje pacijenata sa MDS-om i da bi mogla biti uključena u nove prognostičke skoring sisteme.
Keywords: disulfide; mercaptan; myelodysplasia; oxidative stress; thiol.
2020 Ucar Mehmet Ali, Anıl Tombak, Simten Dagdas, Aydan Akdeniz, Funda Ceran, Salim Neselioglu, Ozcan Erel, Gulsum Ozet, published by CEON/CEES.