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Targeting PTPN2-mediated dephosphorylation destabilizes c-MYC and suppresses acute myeloid leukemia survival

Year: 2026

Type: article

Abstract: Acute myeloid leukemia (AML) is a fatal disease characterized by a bleak prognosis. For over four decades, treatment options for AML have been constrained to administering high-dose cytotoxic chemotherapy. However, the emergence of drug resistance and the resultant toxic side effects have created an urgent necessity for identifying novel therapeutic targets. In this study, non-receptor protein tyrosine phosphatase type 2 (PTPN2) is highly expressed in AML. Remarkably, knockdown of PTPN2 expression markedly mitigated AML burden both in vitro and in vivo. Additionally, we unveiled the direct interaction between PTPN2 and c-MYC, establishing c-MYC as a direct acting substrate of PTPN2. Then, we obtained a small-molecule inhibitor, WS35, which has good inhibitory activity against PTPN2. Moreover, WS35 shows a strong therapeutic effect in vivo for AML. In conclusion, these results indicate the carcinogenic mechanism of PTPN2, and the therapeutic strategies targeting PTPN2 have significant potential for treating AML.

Source: Targetome

DOI: 10.48130/targetome-0026-0052

Authors: Wenbin Kuang, Dawei Wang, Mingge Song, Jianing Liu, Jiaxing Li, Wenmu Wang, Anyan Chen, Ya Chen, Jiayu Ding, Liping Wang, Wanjian Gu, Yibei Xiao, Xiao Wang, Peng Yang

Institutions: China Pharmaceutical University, Jiangsu Province Hospital, Jiangsu Provincial Hospital of Traditional Chinese Medicine, State Key Laboratory of Natural Medicine

Language: English

Topic: Protein Tyrosine Phosphatases

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

OpenAlex ID: W7222648106

FWCI:

Cites: 60

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Related to: 10