Crosstalk between Oxidative Stress, Chronic Inflammation and Disease Progression in Essential Thrombocythemia

2019 ◽  
Vol 70 (10) ◽  
pp. 3486-3489 ◽  
Author(s):  
Amelia Maria Gaman ◽  
Cornel Moisa ◽  
Camelia Cristina Diaconu ◽  
Mihnea Alexandru Gaman
Keyword(s):  
Oxidative Stress ◽  
Disease Progression ◽  
Chronic Inflammation ◽  
Essential Thrombocythemia ◽  
Clonal Evolution ◽  
Myeloproliferative Neoplasm ◽  
Low Grade ◽  
Inflammation Markers ◽  
Leukemic Transformation ◽  
Total Antioxidant

Essential thrombocythemia (ET) is a Philadelphia-negative chronic myeloproliferative neoplasm characterized by acquired somatic mutations: JAK2, CALR or MPL. It is associated with low-grade chronic inflammation, oxidative stress, overproduction of reactive oxygen species (ROS) and antioxidant deficiency. In ET, chronic inflammation and oxidative stress contribute to the genomic instability, the clonal evolution to myelofibrosis and the leukemic transformation. We evaluated ROS levels and the total antioxidant capacity (TAC) in 62 ET patients and investigated the relationship between ROS, TAC, chronic inflammation, leukocytosis, JAK2V617F mutation, and disease progression to myelofibrosis or leukemic transformation. We observed increased levels of ROS and inflammation markers and a decreased TAC in ET patients vs. controls. The acute myeloid leukaemia transformation associated increased levels of oxidative stress and inflammation markers and increased leukocyte counts, while myelofibrosis progression associated an increase in ROS and serum ferritin.

Crosstalk between Oxidative Stress, Chronic Inflammation and Disease Progression in Essential Thrombocythemia

2019 ◽  
Vol 70 (10) ◽  
pp. 3486-3489
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Disease Progression ◽  
Chronic Inflammation ◽  
Essential Thrombocythemia ◽  
Reactive Oxygen ◽  
Low Grade ◽  
Oxygen Species ◽  
Inflammation Markers ◽  
Leukemic Transformation

Essential thrombocythemia (ET) is a Philadelphia-negative chronic myeloproliferative neoplasm characterized by acquired somatic mutations: JAK2, CALR or MPL. It is associated with low-grade chronic inflammation, oxidative stress, overproduction of reactive oxygen species (ROS) and antioxidant deficiency. In ET, chronic inflammation and oxidative stress contribute to the genomic instability, the clonal evolution to myelofibrosis and the leukemic transformation. We evaluated ROS levels and the total antioxidant capacity (TAC) in 62 ET patients and investigated the relationship between ROS, TAC, chronic inflammation, leukocytosis, JAK2V617F mutation, and disease progression to myelofibrosis or leukemic transformation. We observed increased levels of ROS and inflammation markers and a decreased TAC in ET patients vs. controls. The acute myeloid leukaemia transformation associated increased levels of oxidative stress and inflammation markers and increased leukocyte counts, while myelofibrosis progression associated an increase in ROS and serum ferritin. Keywords: essential thrombocythemia, reactive oxygen species, inflammation, JAK2V617F

Oxidative Stress Levels, JAK2V617F Mutational Status and Thrombotic Complications in Patients with Essential Thrombocythemia

2019 ◽  
Vol 70 (8) ◽  
pp. 2822-2825 ◽  
Author(s):  
Cornel Moisa ◽  
Mihnea Alexandru Gaman ◽  
Camelia Cristina Diaconu ◽  
Amelia Maria Gaman
Keyword(s):  
Oxidative Stress ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasm ◽  
Oxygen Species ◽  
Mutational Status ◽  
Increased Risk ◽  
Stress Levels ◽  
Total Antioxidant ◽  
Thrombotic Complications ◽  
The Relationship

Essential thrombocythemia (ET) is a BCR-ABL1-negative myeloproliferative neoplasm associated with thrombotic and haemorrhagic complications. Reactive oxygen species (ROS) overexpression induces a growth advantage to JAK2V617F-positive clones and, in association with a higher number of immature platelets, leukocytosis, and additional cardiovascular risk factors, leads to an increased risk for thrombotic events. We evaluated oxidative stress by measuring ROS levels and the total antioxidant capacity (TAC) in 62 ET patients and investigated the relationship between oxidative stress, JAK2V617F mutational status and the development of thrombotic events. We found higher oxidative stress levels in JAK2V617F-positive vs. JAK2V617F-negative ET cases with no significant differences between homozygous and heterozygous genotypes. Increased ROS levels and thrombotic events were more frequent in ET patients with old age at diagnosis, higher haematocrit levels or leukocytosis.

scholarly journals Synergic Crosstalk between Inflammation, Oxidative Stress, and Genomic Alterations in BCR–ABL-Negative Myeloproliferative Neoplasm

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1037
Author(s):  
Alessandro Allegra ◽  
Giovanni Pioggia ◽  
Alessandro Tonacci ◽  
Marco Casciaro ◽  
Caterina Musolino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cell ◽  
Chronic Inflammation ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Tumor Stage ◽  
Driver Mutations ◽  
Hematopoietic Stem ◽  
Chronic Myeloproliferative Neoplasms ◽  
Inflammatory State

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have recently been revealed to be related to chronic inflammation, oxidative stress, and the accumulation of reactive oxygen species. It has been proposed that MPNs represent a human inflammation model for tumor advancement, in which long-lasting inflammation serves as the driving element from early tumor stage (over polycythemia vera) to the later myelofibrotic cancer stage. It has been theorized that the starting event for acquired stem cell alteration may occur after a chronic inflammation stimulus with consequent myelopoietic drive, producing a genetic stem cell insult. When this occurs, the clone itself constantly produces inflammatory components in the bone marrow; these elements further cause clonal expansion. In BCR–ABL1-negative MPNs, the driver mutations include JAK 2, MPL, and CALR. Transcriptomic studies of hematopoietic stem cells from subjects with driver mutations have demonstrated the upregulation of inflammation-related genes capable of provoking the development of an inflammatory state. The possibility of acting on the inflammatory state as a therapeutic approach in MPNs appears promising, in which an intervention operating on the pathways that control the synthesis of cytokines and oxidative stress could be effective in reducing the possibility of leukemic progression and onset of complications.

Effect of Alpha Lipoic Acid on Oxidative Stress and Chronic Inflammation Markers in Diabetic Older Adults

2017 ◽  
Vol 112 ◽  
pp. 130
Author(s):  
Beatriz Isabel García-Martínez ◽  
Juana Rosado-Pérez ◽  
Mirna Ruiz-Ramos ◽  
Víctor Manuel Mendoza-Núñez
Keyword(s):  
Oxidative Stress ◽  
Older Adults ◽  
Chronic Inflammation ◽  
Lipoic Acid ◽  
Alpha Lipoic Acid ◽  
Inflammation Markers

Obesity and Insulin Resistance: Associations with Chronic Inflammation, Genetic and Epigenetic Factors

2020 ◽  
Vol 27 ◽  
Author(s):  
Amin Gasmi ◽  
Sadaf Noor ◽  
Alain Menzel ◽  
Alexandru Doşa ◽  
Lyudmila Pivina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Chronic Inflammation ◽  
Significant Role ◽  
Genetic Factors ◽  
Low Grade ◽  
Epigenetic Factors ◽  
Plasma Leptin ◽  
Ghrelin Secretion ◽  
Low Grade Inflammation

Background: Obesity is known to be a multifactorial disease. In its pathogenesis, different factors such as chronic inflammation, oxidative stress, insulin resistance, genetic factors, environmental effects, vegetative disturbance, and unbalanced nutrition play a significant role. Methodology: This study describes the association of obesity and insulin resistance with chronic inflammation, genetic, and epigenetic factors. Previous literature has been reviewed to explain the relation of obesity with those factors involved in chronic low-grade inflammation and insulin. Results: Obesity is associated with a decrease in ghrelin secretion, elevated plasma leptin levels, oxidative stress, increased macrophage phagocytic activity, and the induction of pro-inflammatory synthesis of cytokines and interferon-gamma. Obesity is linked to decreased levels of cytochrome P450 (CYP) enzymes and impaired detoxification processes. Deficiency of vitamins and minerals can also play a significant role in the development of oxidative stress and chronic inflammation in obesity. There is evidence of associations between a genetic predisposition to obesity in children with elevated levels of certain miRNAs. Conclusion: The purpose of the present review is an analysis of the multiple factors associated with obesity.

scholarly journals Acute Lymphoblastic Leukemia Arising inCALRMutated Essential Thrombocythemia

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Stephen E. Langabeer ◽  
Karl Haslam ◽  
David O’Brien ◽  
Johanna Kelly ◽  
Claire Andrews ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Lymphoblastic Leukemia ◽  
Myeloproliferative Neoplasm ◽  
Leukemic Transformation ◽  
Distinct Disease ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Disease Entities

The development of acute lymphoblastic leukemia in an existing myeloproliferative neoplasm is rare with historical cases unable to differentiate between concomitant malignancies or leukemic transformation. Molecular studies of coexistingJAK2V617F-positive myeloproliferative neoplasms and mature B cell malignancies indicate distinct disease entities arising in myeloid and lymphoid committed hematopoietic progenitor cells, respectively. Mutations ofCALRin essential thrombocythemia appear to be associated with a distinct phenotype and a lower risk of thrombosis yet their impact on disease progression is less well defined. The as yet undescribed scenario of pro-B cell acute lymphoblastic leukemia arising inCALRmutated essential thrombocythemia is presented. Intensive treatment for the leukemia allowed for expansion of the originalCALRmutated clone. WhetherCALRmutations in myeloproliferative neoplasms predispose to the acquisition of additional malignancies, particularly lymphoproliferative disorders, is not yet known.

Oxidative Stress and BCR-ABL1 Transcript Levels in Chronic Myeloid Leukemia: an Intricate Relationship

2019 ◽  
Vol 70 (9) ◽  
pp. 3193-3196 ◽  
Author(s):  
Emilia Georgiana Pascu ◽  
Mihnea Alexandru Gaman ◽  
Cornel Moisa ◽  
Amelia Maria Gaman
Keyword(s):  
Oxidative Stress ◽  
Chronic Myeloid Leukemia ◽  
Disease Progression ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Neoplasm ◽  
Compensatory Mechanism ◽  
Stress Levels ◽  
Tki Treatment

Chronic myeloid leukemia (CML) is a chronic myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome. Oxidative stress is involved in CML etiopathogenesis and disease progression, as well as the response to tyrosine kinase inhibitors (TKI) treatment. We evaluated oxidative stress levels in 47 CML patients vs. controls. The total antioxidant capacity (TAC) was measured using a FLUOstar Omega microplate reader (reagents from Sigma-Aldrich). Cellular reactive oxygen species (ROS) were evaluated using a CyFlow SPACE Sysmex flow-cytometer (reagents from Abcam). Oxidative stress levels were higher in CML patients vs. controls. The maximum TAC value and the minimum ROS value were recorded in CML patients with a BCR-ABL1 transcript value of 0.1-1%, suggesting that the production of plasma antioxidants progressively increases as a compensatory mechanism in CML patients undergoing TKI treatment in order to annihilate ROS. The pseudonormalization of the cell redox status observed in these patients could be an alarm signal prior to the development of resistance to TKI treatment or disease progression.

scholarly journals Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer?

Blood ◽  
2012 ◽  
Vol 119 (14) ◽  
pp. 3219-3225 ◽  
Author(s):  
Hans Carl Hasselbalch
Keyword(s):  
Polycythemia Vera ◽  
Chronic Inflammation ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Bone Marrow Failure ◽  
Clonal Evolution ◽  
Disease Stage ◽  
Common Denominator ◽  
Second Cancer ◽  
Accelerated Atherosclerosis

Abstract The morbidity and mortality of patients with the chronic Philadelphia-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia, polycythemia vera, and primary myelofibrosis are mainly caused by cardiovascular diseases, thrombohemorrhagic complications, and bone marrow failure because of myelofibrosis and leukemic transformation. In the general population, chronic inflammation is considered of major importance for the development of atherosclerosis and cancer. MPNs are characterized by a state of chronic inflammation, which is proposed to be the common denominator for the development of “premature atherosclerosis,” clonal evolution, and second cancer in patients with MPNs. Chronic inflammation may both initiate clonal evolution and catalyze its expansion from early disease stage to the myelofibrotic burnt-out phase. Furthermore, chronic inflammation may also add to the severity of cardiovascular disease burden by accelerating the development of atherosclerosis, which is well described and recognized in other chronic inflammatory diseases. A link between chronic inflammation, atherosclerosis, and second cancer in MPNs favors early intervention at the time of diagnosis (statins and interferon-α2), the aims being to dampen chronic inflammation and clonal evolution and thereby also diminish concurrent disease-mediated chronic inflammation and its consequences (accelerated atherosclerosis and second cancer).

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