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Citations to this article

Loss of pleckstrin-2 reverts lethality and vascular occlusions in JAK2V617F-positive myeloproliferative neoplasms
Baobing Zhao, … , Charles S. Abrams, Peng Ji
Baobing Zhao, … , Charles S. Abrams, Peng Ji
Published November 20, 2017
Citation Information: J Clin Invest. 2018;128(1):125-140. https://doi.org/10.1172/JCI94518.
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Research Article Hematology Article has an altmetric score of 13

Loss of pleckstrin-2 reverts lethality and vascular occlusions in JAK2V617F-positive myeloproliferative neoplasms

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Abstract

V617F driver mutation of JAK2 is the leading cause of the Philadelphia-chromosome-negative myeloproliferative neoplasms (MPNs). Although thrombosis is a leading cause of mortality and morbidity in MPNs, the mechanisms underlying their pathogenesis are unclear. Here, we identified pleckstrin-2 (Plek2) as a downstream target of the JAK2/STAT5 pathway in erythroid and myeloid cells, and showed that it is upregulated in a JAK2V617F-positive MPN mouse model and in patients with MPNs. Loss of Plek2 ameliorated JAK2V617F-induced myeloproliferative phenotypes including erythrocytosis, neutrophilia, thrombocytosis, and splenomegaly, thereby reverting the widespread vascular occlusions and lethality in JAK2V617F-knockin mice. Additionally, we demonstrated that a reduction in red blood cell mass was the main contributing factor in the reversion of vascular occlusions. Thus, our study identifies Plek2 as an effector of the JAK2/STAT5 pathway and a key factor in the pathogenesis of JAK2V617F-induced MPNs, pointing to Plek2 as a viable target for the treatment of MPNs.

Authors

Baobing Zhao, Yang Mei, Lan Cao, Jingxin Zhang, Ronen Sumagin, Jing Yang, Juehua Gao, Matthew J. Schipma, Yanfeng Wang, Chelsea Thorsheim, Liang Zhao, Timothy Stalker, Brady Stein, Qiang Jeremy Wen, John D. Crispino, Charles S. Abrams, Peng Ji

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 Total
Citations: 1 4 1 5 8 3 2 24
Citation information
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Citations to this article in year 2020 (3)

Title and authors Publication Year
Endothelial JAK2V617F mutation leads to thrombosis, vasculopathy, and cardiomyopathy in a murine model of myeloproliferative neoplasm
M Castiglione, YP Jiang, C Mazzeo, S Lee, JS Chen, K Kaushansky, W Yin, RZ Lin, H Zheng, H Zhan
Journal of Thrombosis and Haemostasis 2020
Platelet Dysfunction and Thrombosis in JAK2 V617F -Mutated Primary Myelofibrotic Mice
S Matsuura, CR Thompson, ME Belghasem, RH Bekendam, A Piasecki, O Leiva, A Ray, J Italiano, M Yang, G Merill-Skoloff, VC Chitalia, R Flaumenhaft, K Ravid
Arteriosclerosis, thrombosis, and vascular biology 2020
PLEK2 Gene Upregulation Might Independently Predict Shorter Progression-Free Survival in Lung Adenocarcinoma
W Zhang, T Li, B Hu, H Li
Technology in cancer research & treatment 2020

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ISSN: 0021-9738 (print), 1558-8238 (online)

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