Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia

Abstract

Chronic inflammation is characterized by the production of reactive oxygen species (ROS), reactive nitrogen species, and inflammatory cytokines in myeloproliferative neoplasms (MPNs). In addition to these parameters, the aim of this study was to analyze the influence of ROS on the proliferation-related AKT/mTOR signaling pathway and the relationship with inflammatory factors in chronic myelogenous leukemia (CML). The activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase is reduced in erythrocytes while levels of the oxidative stress markers malondialdehyde and protein carbonyl are elevated in the plasma of patients with CML. In addition, nitrogen species (nitrotyrosine, iNOS, eNOS) and inflammation markers (IL-6, NFkB, and S100 protein) were increased in granulocytes of CML while anti-inflammatory levels of IL-10 were decreased in plasma. CML granulocytes exhibited greater resistance to cytotoxic H2O2 activity compared to healthy subjects. Moreover, phosphorylation of the apoptotic p53 protein was reduced while the activity of the AKT/mTOR signaling pathway was increased, which was further enhanced by oxidative stress (H2O2) in granulocytes and erythroleukemic K562 cells. IL-6 caused oxidative stress and DNA damage that was mitigated using antioxidant or inhibition of inflammatory NFkB transcription factor in K562 cells. We demonstrated the presence of oxidative and nitrosative stress in CML, with the former mediated by AKT/mTOR signaling and stimulated by inflammation.

IgA monoclonal gammopathies are accompanied with higher serum TGF-β1 levels than IgG or IgM monoclonal gammopathies – screening study

“…It is known that infectious pathogens are associated with diverse B-cell malignancies, either through direct cell infection leading to transformation or via antigen (Ag)-induced stimulation causing indirect cell transformation, or a combination of both mechanisms. Chronic cancer-associated in ammation is established in hematological malignancies, especially in myeloma [33] and chronic myeloproliferative neoplasms (MPNs) [34,35]. In the case of monoclonal gammopathy of undetermined signi cance (MGUS), where the paraprotein level is < 30 g/L and the monoclonal immunoglobulin may constitute 20-70% of total immunoglobulin, the production of polyclonal IgG is sustained [36].…”

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

“…In addition, other types of measurements, e.g., ROS quantification, require the immediate evaluation of fresh samples due to the quick degradation of ROS, and thus, this type of assessment could not be conducted using frozen plasma. However, we plan to address these limitations in future prospective studies, in which we will collect more blood components and other types of samples (e.g., urine) from MPN and sAML patients to analyze more markers of oxidative and nitrosative stress, inflammation levels, antioxidant enzymes, neutrophil extracellular traps, and other biomarkers [ 33 , 34 ]. In addition, as extensive genetic testing was only available in a limited number of cases, particularly in sAML patients, several observations need to be interpreted with caution and require validation in future assessments.…”

Sex-dependent effects of chronic intermittent hypoxia: implication for obstructive sleep apnea

“…Hypoxia induced by OSA is observed to increase many circulating markers of OS and inflammation [ 13 – 18 ]. This can induce a feed-forward cycle, in which chronic inflammation increases OS [ 35 , 36 ], and chronic OS can increase inflammation [ 37 , 38 ]. In addition, sex also plays a role in OS and inflammation [ 39 , 40 ].…”