Document Type
Article
Publication Date
6-25-2026
Department
Biology
Keywords
Myeloid Neoplasia, cancer, transplant, cells
Abstract
Acute myeloid leukemia (AML) is an aggressive hematological malignancy that is sustained by leukemia-initiating cells (LICs). Although protein tyrosine phosphatase 4A2 (PTP4A2), also known as phosphatase of regenerating liver 2 (PRL2), is highly expressed in AML, the mechanisms by which PTP4A2 promotes leukemogenesis are largely unexplored. In this study, we demonstrate that PTP4A2 promotes AML by inhibiting the p53 tumor suppressor pathway in LICs. Using KMT2A-MLLT3–driven AML as a model, we found that PTP4A2 deficiency activates p53 and induces LIC apoptosis and senescence, thereby extending the survival of recipient mice repopulated with Ptp4a2−/− LICs. Mechanistically, PTP4A2 directly interacts with p53 and dephosphorylates it at serine 392, decreasing p53 stability and activity to enhance LIC proliferation and survival. Collectively, our findings identify p53 as a potential PTP4A2 substrate in leukemia cells and uncover a novel mechanism by which PTP4A2 enhances LIC maintenance.
Source Publication Title
Blood Advances
Publisher
American Society of Hematology
Volume
10
Issue
13
First Page
4468
DOI
https://doi.org/10.1182/bloodadvances.2025018908
Recommended Citation
Xiao, S., Kobayashi, M., Bai, Y., Cai, W., Barajas, S., Amin, M. A., Vemula, S., Yao, C., Yang, Y., & Borchers, C. (2026). PTP4A2 Promotes Leukemogenesis Through Inhibiting the p53 Tumor Suppressor Signaling Pathway in Leukemia-Initiating Cells. Blood Advances, 10 (13), 4468. https://doi.org/https://doi.org/10.1182/bloodadvances.2025018908
Comments
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Published in Blood Advances
PTP4A2 promotes Leukemogenesis Through Inhibiting