ORIGINAL RESEARCH article
Front. Hematol.
Sec. Blood Cancer
Volume 4 - 2025 | doi: 10.3389/frhem.2025.1479185
Down-regulated PTEN and aberrant JAK-STAT Signal Pathway in Essential Thrombocythemia Patients
Provisionally accepted
- 1Phase I clinical trial laboratory, Zhongnan Hospital, Wuhan University, Wuhan, Hubei Province, China
- 2Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China
- 3Department of Cardiology, Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, Hebei, China
- 4Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zheng zhou, China
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Background: Essential thrombocythemia (ET) is one of the Philadelphia-negative (ph-) classical myeloproliferative neoplasms (MPNs), characterized by increased megakaryocytes and platelet counts, also with an increased risk of thrombo-hemorrhagic complications. The JAK2 V617F mutation is detected in 50%-60% of ET patients and can drive ET occurrence through ligand-independent activation of the thrombopoietin (TPO) receptor, resulting in JAK/STAT pathway signaling. Phosphatase and tensin homolog (PTEN) was found to be associated with many hematologic diseases, especially in MPNs, and involved in JAK/STAT pathway. This study aims to determine the role of PTEN in ET patients with the JAK2 V617F mutation. Methods: In this study, we have analyzed a series of 32 ET patients without treatment and 25 age- and sex-matched normal controls for the detection of PTEN expression and STT motif phosphorylated of PTEN, as well as the expression pattern of STAT3 and STAT5 and their phosphorylated molecules (p-STAT3 and p-STAT5, respectively) of the bone marrow mononuclear cells (BM-MNCs) by immunohistochemical staining of bone marrow biopsies (IHC) and western blot. Correlations between PTEN expression and other clinical characteristics were also studied. Results: The results showed that down-regulated PTEN expression in the BM-MNCs of ET patients, as well as elevated p-STAT3 expression and decreased p-STAT5 expression. Additionally, analysis in combination with clinical data demonstrated a negative correlation between PTEN expression and patients' age, as well as platelet counts. In contrast, a positive correlation was detected between PTEN expression and p-STAT5 expression level. Conclusions: Our results suggest that aberrant PTEN expression and JAK/STAT pathway signaling might be involved in the onset of ET disease. Our findings might shed new light on the pathogenesis and treatment of ET.
Keywords: Essential thrombocythemia, Myeloproliferative neoplasms, Pten, stat3, Stat5
Received: 11 Aug 2024; Accepted: 23 Apr 2025.
Copyright: © 2025 Luo, Liu, Shen, Zhang, Shang, Zhang, Fuling and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xian Zhang, Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China
Zhou Fuling, Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China
Donglei Zhang, Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China
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