Assessment of Total Antioxidant Capacity, 8-Hydroxy-2'-deoxy-guanosine, the Genetic Landscape, and Their Associations in BCR::ABL-1 -Negative Chronic and Blast Phase Myeloproliferative Neoplasms

• Published in: International journal of molecular sciences 2024-06, Vol.25 (12), p.6652
• Main Authors: Găman, Mihnea-Alexandru, Mambet, Cristina, Neagu, Ana Iulia, Bleotu, Coralia, Gurban, Petruta, Necula, Laura, Botezatu, Anca, Ataman, Marius, Diaconu, Camelia Cristina, Ionescu, Bogdan Octavian, Ghiaur, Alexandra Elena, Tatic, Aurelia, Coriu, Daniel, Găman, Amelia Maria, Diaconu, Carmen Cristina
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2'-Deoxyguanosine - metabolism; 8-hydroxy-2′-deoxy-guanosine; Adult; Aged; Aged, 80 and over; Analysis; antioxidant capacity; Antioxidants; Antioxidants - metabolism; Biology; Blast Crisis - genetics; Blast Crisis - metabolism; Blast Crisis - pathology; Development and progression; Female; Fusion Proteins, bcr-abl - genetics; Fusion Proteins, bcr-abl - metabolism; Genes; Genetic testing; Genotype & phenotype; Hemoglobin; Humans; Kinases; leukemic transformation; Male; Middle Aged; Mutation; Myeloproliferative Disorders - genetics; Myeloproliferative Disorders - metabolism; Myeloproliferative Disorders - pathology; myeloproliferative neoplasms; Oxidative Stress; Primary Myelofibrosis - genetics; Primary Myelofibrosis - metabolism; Primary Myelofibrosis - pathology; Reactive oxygen species; secondary acute myeloid leukemia; Stem cells; Tumors; Type 2 diabetes
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25126652

Myeloproliferative neoplasms (MPNs), namely, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal stem cell disorders defined by an excessive production of functionally mature and terminally differentiated myeloid cells. MPNs can transform into secondary acute myeloid leukemia (sAML/blast phase MPN) and are linked to alterations in the redox balance, i.e., elevated concentrations of reactive oxygen species and markers of oxidative stress (OS), and changes in antioxidant systems. We evaluated OS in 117 chronic phase MPNs and 21 sAML cases versus controls by measuring total antioxidant capacity (TAC) and 8-hydroxy-2'-deoxy-guanosine (8-OHdG) concentrations. TAC was higher in MPNs than controls ( = 0.03), particularly in ET ( = 0.04) and PMF ( = 0.01). -positive MPNs had higher TAC than controls ( = 0.002) and triple-negative MPNs ( = 0.01). PMF patients who had treatment expressed lower TAC than therapy-free subjects ( = 0.03). 8-OHdG concentrations were similar between controls and MPNs, controls and sAML, and MPNs and sAML. We noted associations between TAC and MPNs (OR = 1.82; = 0.05), i.e., ET (OR = 2.36; = 0.03) and PMF (OR = 2.11; = 0.03), but not sAML. 8-OHdG concentrations were not associated with MPNs (OR = 1.73; = 0.62) or sAML (OR = 1.89; = 0.49). In conclusion, we detected redox imbalances in MPNs based on disease subtype, driver mutations, and treatment history.