Data from Reduced Platelet Activation in Triple-Negative Essential Thrombocythemia Compared with <i>JAK2V617F</i>-Mutated Essential Thrombocythemia

• DOI: 10.1158/1078-0432.c.7565449
• Publication Date: 2024-12-02T08:21:04Z
• Authors: Huan Dong; Jia Chen; Jing Zhang; Feng Xue; Huiyuan Li; Donglei Zhang; Hu Zhou; Xian Zhang; Yueting Huang; Xiaofan Liu; Yunfei Chen; Wei Liu; Ying Chi; Wentian Wang; Ting Sun; Mankai Ju; Xinyue Dai; Wenjing Gu; Renchi Yang; Rongfeng Fu; Lei Zhang

<div>AbstractPurpose:<p>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.</p>Experimental Design:<p>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.</p>Results:<p>Compared with patients with the <i>JAK2V617F</i> mutation, those with TN mutation were younger (<i>P</i> < 0.001) and exhibited fewer thrombotic events before diagnosis (<i>P</i> < 0.001) and during follow-up (<i>P</i> = 0.039). Patients with TN mutation also presented with significantly reduced CD62P expression in platelets (<i>P</i> = 0.031), slightly reduced calcium concentration in platelets (<i>P</i> = 0.063), increased mitochondrial membrane potential (<i>P</i> = 0.011), reduced phosphatidylserine exposure (<i>P</i> = 0.015), reduced levels of ROS (<i>P</i> = 0.043) and MitoSOX in platelets (<i>P</i> = 0.047).</p>Conclusions:<p>In comparison with <i>JAK2V617F</i>-mutated ET, TN-ET is associated with lower platelet ROS levels, which leads to reduced platelet activation and consequently a lower risk of thrombosis.</p></div>