Journal of thrombosis and haemostasis : JTH · 2026
Dysregulation of HIF-1α-regulated and thromboinflammatory genes may contribute to thrombotic risk in patients with BCR::ABL1-negative myeloproliferative neoplasms.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Morath Olga, Wolfrum Therese, Crodel Carl, Hochhaus Andreas, Ernst Thomas, Rinke Jenny
Аннотация
BACKGROUND: Hypoxia-inducible factor-1α (HIF-1α) regulates multiple pathways involved in metabolism, inflammation, and coagulation and may contribute to thrombotic complications in patients with BCR::ABL1-negative myeloproliferative neoplasms (MPN).
OBJECTIVES: This study aimed to investigate the expression of selected HIF-1α-regulated and thromboinflammatory genes (SLC2A1, F3, SELP, VEGFA, SERPINE1, PROS1, NLRP3, and THBS1) and their association with thrombotic events, JAK2 mutation status, and cytoreductive therapy.
METHODS: Data of 120 patients with MPN (40 with polycythemia vera, 40 with essential thrombocythemia, and 40 with primary myelofibrosis) and their blood samples were analyzed. In each MPN subtype, 50% of patients had a history of thrombosis. RNA expression levels were measured using quantitative reverse transcription polymerase chain reaction.
RESULTS: RNA expression patterns differed across MPN subtypes. Higher F3 expression in essential thrombocythemia and increased SLC2A1 and SELP expression in polycythemia vera and primary myelofibrosis were observed in patients with thrombosis. In multivariable logistic regression, SLC2A1 (odds ratio [OR], 2.05; 95% CI, 1.20-3.49; P = .008) and SELP expression (OR, 1.79; 95% CI, 1.06-3.02; P = .03) remained independently associated with thrombotic events, whereas NLRP3 expression was inversely associated (OR, 0.58; 95% CI, 0.37-0.90; P = .02). Most analyzed genes were more highly expressed in patients with JAK2 mutation than in JAK2-negative patients. Cytoreductive therapy showed no significant impact on RNA expression.
CONCLUSION: Subtype-specific RNA expression patterns may reflect differences in thrombotic incidence across MPN entities. Higher RNA expression in patients with JAK2 mutation supports a link between JAK2 signaling and HIF-related pathways. Further studies are warranted to clarify their role and therapeutic potential.
OBJECTIVES: This study aimed to investigate the expression of selected HIF-1α-regulated and thromboinflammatory genes (SLC2A1, F3, SELP, VEGFA, SERPINE1, PROS1, NLRP3, and THBS1) and their association with thrombotic events, JAK2 mutation status, and cytoreductive therapy.
METHODS: Data of 120 patients with MPN (40 with polycythemia vera, 40 with essential thrombocythemia, and 40 with primary myelofibrosis) and their blood samples were analyzed. In each MPN subtype, 50% of patients had a history of thrombosis. RNA expression levels were measured using quantitative reverse transcription polymerase chain reaction.
RESULTS: RNA expression patterns differed across MPN subtypes. Higher F3 expression in essential thrombocythemia and increased SLC2A1 and SELP expression in polycythemia vera and primary myelofibrosis were observed in patients with thrombosis. In multivariable logistic regression, SLC2A1 (odds ratio [OR], 2.05; 95% CI, 1.20-3.49; P = .008) and SELP expression (OR, 1.79; 95% CI, 1.06-3.02; P = .03) remained independently associated with thrombotic events, whereas NLRP3 expression was inversely associated (OR, 0.58; 95% CI, 0.37-0.90; P = .02). Most analyzed genes were more highly expressed in patients with JAK2 mutation than in JAK2-negative patients. Cytoreductive therapy showed no significant impact on RNA expression.
CONCLUSION: Subtype-specific RNA expression patterns may reflect differences in thrombotic incidence across MPN entities. Higher RNA expression in patients with JAK2 mutation supports a link between JAK2 signaling and HIF-related pathways. Further studies are warranted to clarify their role and therapeutic potential.
Предметные рубрики MeSH
HumansFemaleThrombosisJanus Kinase 2MaleMiddle AgedRisk FactorsMutationHypoxia-Inducible Factor 1, alpha SubunitMyeloproliferative DisordersAgedGenetic Predisposition to DiseaseFusion Proteins, bcr-ablAdultThrombocythemia, EssentialPolycythemia VeraPrimary MyelofibrosisInflammationNLR Family, Pyrin Domain-Containing 3 Protein