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Войти в исследования Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
Reduced Platelet Activation in Triple-Negative Essential Thrombocythemia Compared with JAK2V617F-Mutated Essential Thrombocythemia.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Dong Huan, Chen Jia, Zhang Jing, Xue Feng, Li Huiyuan, Zhang Donglei, Zhou Hu, Zhang Xian, Huang Yueting, Liu Xiaofan, Chen Yunfei, Liu Wei, Chi Ying, Wang Wentian, Sun Ting, Ju Mankai, Dai Xinyue, Gu Wenjing, Yang Renchi, Fu Rongfeng, Zhang Lei
Аннотация
PURPOSE: Triple-negative (TN) essential thrombocytopenia (ET) is characterized by the absence of driver mutations while retaining histologic and phenotypic characteristics sufficient for an ET diagnosis. Our understanding of TN-ET and its platelet activation remains incomplete. We carried out a large-scale multicenter clinical analysis to analyze the clinical and molecular characteristics and thrombotic complications of TN-ET. We also related the above characteristics to platelet activation to further explore the thrombosis mechanism of TN-ET.
EXPERIMENTAL DESIGN: A retrospective multicenter study was conducted on 138 patients with TN-ET and 759 patients with ET with driver mutations from March 1, 2012 to December 1, 2021. The clinical and molecular characteristics of the patients with TN-ET were summarized. Additionally, platelet activation, apoptosis, and reactive oxygen species (ROS) levels were analyzed in 73 patients with TN-ET from this cohort and compared with 41 age- and sex-matched healthy donors.
RESULTS: Compared with patients with the JAK2V617F mutation, those with TN mutation were younger (P < 0.001) and exhibited fewer thrombotic events before diagnosis (P < 0.001) and during follow-up (P = 0.039). Patients with TN mutation also presented with significantly reduced CD62P expression in platelets (P = 0.031), slightly reduced calcium concentration in platelets (P = 0.063), increased mitochondrial membrane potential (P = 0.011), reduced phosphatidylserine exposure (P = 0.015), reduced levels of ROS (P = 0.043) and MitoSOX in platelets (P = 0.047).
CONCLUSIONS: In comparison with JAK2V617F-mutated ET, TN-ET is associated with lower platelet ROS levels, which leads to reduced platelet activation and consequently a lower risk of thrombosis.
EXPERIMENTAL DESIGN: A retrospective multicenter study was conducted on 138 patients with TN-ET and 759 patients with ET with driver mutations from March 1, 2012 to December 1, 2021. The clinical and molecular characteristics of the patients with TN-ET were summarized. Additionally, platelet activation, apoptosis, and reactive oxygen species (ROS) levels were analyzed in 73 patients with TN-ET from this cohort and compared with 41 age- and sex-matched healthy donors.
RESULTS: Compared with patients with the JAK2V617F mutation, those with TN mutation were younger (P < 0.001) and exhibited fewer thrombotic events before diagnosis (P < 0.001) and during follow-up (P = 0.039). Patients with TN mutation also presented with significantly reduced CD62P expression in platelets (P = 0.031), slightly reduced calcium concentration in platelets (P = 0.063), increased mitochondrial membrane potential (P = 0.011), reduced phosphatidylserine exposure (P = 0.015), reduced levels of ROS (P = 0.043) and MitoSOX in platelets (P = 0.047).
CONCLUSIONS: In comparison with JAK2V617F-mutated ET, TN-ET is associated with lower platelet ROS levels, which leads to reduced platelet activation and consequently a lower risk of thrombosis.