Clinical Correlates and Prognostic Significance of IL-8, sIL-2R, and Immunoglobulin-Free Light Chain Levels in Patients with Myelofibrosis

Barabanshikova, Maria V.; Dubina, Irina A; Лапин, С. В.; Morozova, Elena; Vlasova, Julia J.; Ivanova, Maria; Moiseev, Ivan S.; Afanasyev, Boris

doi:10.1159/000477253

Cited by 12 publications

(9 citation statements)

References 17 publications

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“…Studies by Tefferi and colleagues revealed elevated serum levels of IL-1β in PV (n = 65) and PMF (n = 127) patient cohorts [ 21 , 28 ]. Furthermore, elevated levels of IL-12, IL-15, IP-10, IL-8, IL-2, and s-IL-2R in PMF patients have been correlated with decreased/poor overall survival [ 21 , 28 , 57 ]. Other very important participating factors, the NLRP3 and AIM2 inflammasomes, have appeared as crucial players in regulating certain hematological pathologies, e.g., myelodysplastic syndrome (MDS), MPNs, cardiovascular risk, and leukemia [ 58 , 59 ].…”

Section: Inflammatory Cytokinesmentioning

confidence: 99%

Thromboinflammation in Myeloproliferative Neoplasms (MPN)—A Puzzle Still to Be Solved

Bhuria

Baldauf

Schraven

et al. 2022

IJMS

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Myeloproliferative neoplasms (MPNs), a group of malignant hematological disorders, occur as a consequence of somatic mutations in the hematopoietic stem cell compartment and show excessive accumulation of mature myeloid cells in the blood. A major cause of morbidity and mortality in these patients is the marked prothrombotic state leading to venous and arterial thrombosis, including myocardial infarction (MI), deep vein thrombosis (DVT), and strokes. Additionally, many MPN patients suffer from inflammation-mediated constitutional symptoms, such as fever, night sweats, fatigue, and cachexia. The chronic inflammatory syndrome in MPNs is associated with the up-regulation of various inflammatory cytokines in patients and is involved in the formation of the so-called MPN thromboinflammation. JAK2-V617F, the most prevalent mutation in MPNs, has been shown to activate a number of integrins on mature myeloid cells, including granulocytes and erythrocytes, which increase adhesion and drive venous thrombosis in murine knock-in/out models. This review aims to shed light on the current understanding of thromboinflammation, involvement of neutrophils in the prothrombotic state, plausible molecular mechanisms triggering the process of thrombosis, and potential novel therapeutic targets for developing effective strategies to reduce the MPN disease burden.

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Section: Inflammatory Cytokinesmentioning

confidence: 99%

Thromboinflammation in Myeloproliferative Neoplasms (MPN)—A Puzzle Still to Be Solved

Bhuria

Baldauf

Schraven

et al. 2022

IJMS

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“…In other studies on MF subjects, the correlation of specific cytokines with lower survival (IL2R, IL8), transfusion dependence (IL2R, IL8), higher number of leukocytes (IL2R), circulating blasts (IL-8), lower platelet count (IP10), and JAK2V617F positivity (IL2R) was demonstrated [44]. All of these findings represent factors independent from those used in the clinical Dynamic International Prognostic Scoring System (DIPSS).…”

Section: Rantesmentioning

confidence: 76%

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

et al. 2020

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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.

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“…Previous studies have identified that the serum (and/or plasma) of patients with MF contains greater levels of several proinflammatory cytokines than that of nondiseased individuals. More specifically, the plasma of these patients contains greater levels of TGF-β, both as total and activated form [ 7 ], and interleukin-8 (IL-8), and the plasma levels of IL-8 were found to predict the severity of the symptoms and progression to leukemic transformation [ 8 , 9 ]. Both TGF-β and IL-8 are abnormally produced at high levels by the megakaryocytes present in the bone marrow of myelofibrosis patients [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Resident Self-Tissue of Proinflammatory Cytokines Rather Than Their Systemic Levels Correlates with Development of Myelofibrosis in Gata1low Mice

et al. 2022

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Serum levels of inflammatory cytokines are currently investigated as prognosis markers in myelofibrosis, the most severe Philadelphia-negative myeloproliferative neoplasm. We tested this hypothesis in the Gata1low model of myelofibrosis. Gata1low mice, and age-matched wild-type littermates, were analyzed before and after disease onset. We assessed cytokine serum levels by Luminex-bead-assay and ELISA, frequency and cytokine content of stromal cells by flow cytometry, and immunohistochemistry and bone marrow (BM) localization of GFP-tagged hematopoietic stem cells (HSC) by confocal microscopy. Differences in serum levels of 32 inflammatory-cytokines between prefibrotic and fibrotic Gata1low mice and their wild-type littermates were modest. However, BM from fibrotic Gata1low mice contained higher levels of lipocalin-2, CXCL1, and TGF-β1 than wild-type BM. Although frequencies of endothelial cells, mesenchymal cells, osteoblasts, and megakaryocytes were higher than normal in Gata1low BM, the cells which expressed these cytokines the most were malignant megakaryocytes. This increased bioavailability of proinflammatory cytokines was associated with altered HSC localization: Gata1low HSC were localized in the femur diaphysis in areas surrounded by microvessels, neo-bones, and megakaryocytes, while wild-type HSC were localized in the femur epiphysis around adipocytes. In conclusion, bioavailability of inflammatory cytokines in BM, rather than blood levels, possibly by reshaping the HSC niche, correlates with myelofibrosis in Gata1low mice.

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Clinical Correlates and Prognostic Significance of IL-8, sIL-2R, and Immunoglobulin-Free Light Chain Levels in Patients with Myelofibrosis

Cited by 12 publications

References 17 publications

Thromboinflammation in Myeloproliferative Neoplasms (MPN)—A Puzzle Still to Be Solved

Thromboinflammation in Myeloproliferative Neoplasms (MPN)—A Puzzle Still to Be Solved

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

Resident Self-Tissue of Proinflammatory Cytokines Rather Than Their Systemic Levels Correlates with Development of Myelofibrosis in Gata1low Mice

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