Photo Credit: Nemes Laszlo
Altered serum metabolites in primary MF present opportunities for antioxidant therapy, as patients with PMF have a different metabolic makeup.
The median overall survival rate of patients diagnosed with primary myelofibrosis (PMF) is between 6-7 years. Common causes of mortality in these patients are leukemic transformation, vascular events, and infections. Studies have shown that inflammation related to the overproduction of cytokines is a significant contributor to the disease’s pathogenesis and progression; oxidative stress has also been noted as a contributor to PMF’s development to acute myeloid leukemia.
Since no known examination has been made regarding the levels of circulating antioxidants in patients with PMF, Barbara Tavazzi, PhD, and colleagues developed a study applying a targeted metabolic approach that compared the blood samples of patients with PMF to a group of healthy patients who served as controls. As written by Dr. Tavazzi and colleagues in Antioxidants, where the findings of the study were published, “Herein, we undertook the present study to quantitatively measure water-soluble antioxidants, purines, pyrimidines, and oxidative/nitrosative stress biomarkers in serum samples of [patients with] PMF to find correlations with parameters reflecting their clinical conditions and possibly highlighting new biochemical dysfunctions characterizing [patients with] PMF.”
Twenty-two patients with PMF and 22 healthy controls were identified for inclusion in the study. Of the patients with PMF, 68% were male, and the median age was 68, with a range of 41-76. Of the health controls, 13% were male, and the median age was 63, ranging from 31 to 75.
Higher Rates in PMF Cohort
The mean circulating levels of ascorbic acid in the cohort of patients with PMF were 1.13 ±0.93 μmol/L serum. By comparison, the mean values in the control group were 42.19 ±13.05 μmol/L serum, a 37.3-fold decrease (P<0.001). As for glutathione, in the serum of patients in the PMF cohort, the value was 6.68 ±2.64 μmol/L serum. This was a 3.81-fold decrease (P<0.001) compared to the mean values recorded in the healthy control group, which were 25.48 ±6.78 μmol/L serum. The mean levels of serum malondialdehyde in patients within the PMF cohort was 0.52 ±0.34 μmol/L; this was an increase of 4.73-fold (P<0.001) when compared with the mean values of the healthy control group (0.11 ±0.06 μmol/L). The researchers noted that nitrosative stress was evident in the 1.66-fold increase of the nitrite + nitrate serum concentrations in the PMF cohort compared to the values found in the healthy control group (P<0.003).
In the PMF cohort, circulating concentrations of hypoxanthine in the serum were 33.77 ±20.77 μmol/L; the healthy control group was lower with 5.97 ±1.81 μmol/L (P<0.001). In the PMF cohort, the serum levels of xanthine were 5.26 ±2.82 μmol/L, and the serum levels of uric acid were 505.12 ±153.34 μmol/L. This was a marked increase compared to the values in the healthy control group—3.19 ±1.22 μmol/L for xanthine (P<0.01) and 306.08 ±65.19 μmol/L for uric acid (P<0.001).
The PMF cohort had a higher sum of circulating oxypurines, which included hypoxanthine + xanthine + uric acid; these stemmed from the degradation pathway of purine nucleotides. The sum was 544.26 ±149.64 μmol/L in the PMF cohort and 319.11 ±66.96 μmol/L in the healthy control group (P<0.001).
PMF Cohort Subgroups
The researcher also examined subgroups within the PMF cohort. Those patients in the PMF cohort who were aged 68 years or younger had a serum hypoxanthine value of 19.63 ±8.52 μmol/L, whereas the value recorded in PMF cohort participants older than age 68 was 44.31 ±28.26 μmol/L (P<0.024). In terms of serum creatinine values, males had a value of 118.87 ±42.65 μmol/L compared to the concentrations detected in the female PMF cohort participants, which were 80.55 ±33.39 μmol/L (P<0.004).
In terms of clinical characteristics, PMF cohort participants with lower-grade bone marrow (BM) fibrosis had serum uridine concentrations of 13.63 ±6.72 μmol/L, and those with higher-grade BM fibrosis had concentrations of 7.45 ±2.12 μmol/L. Those PMF cohort participants in a lower-risk class, according to the International Prostate Symptom Score (IPSS), had a nitrate sum of 104.88 ±44.43 μmol/L, and those in a higher-risk class, according to IPSS, had a nitrate sum of 56.99 ±33.14 μmol/L (P<0.02). Uracil levels in the IPSS lower-risk class were 5.22 ±1.84 and 3.92 ±2.17 μmol/L for the higher-risk class (P<0.04).
