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Peer-reviewedCC BYTargetome

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

  • Wenbin Kuang1
  • Dawei Wang1
  • Mingge Song1
  • Jianing Liu1
  • Jiaxing Li1
  • Wenmu Wang1
  • Anyan Chen1
  • Ya Chen2
  • Jiayu Ding1
  • Liping Wang1
  • Wanjian Gu3
  • Yibei Xiao1
2 more authors
  • Xiao Wang1
  • Peng Yang1
  1. 1State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China
  2. 2Institute of Innovative Drug, China Pharmaceutical University, Nanjing 211198, China
  3. 3Department of Clinical Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
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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.

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Cite

BibTeXRIS
BibTeX
@article{kuang2026targeting,
  title = {{Targeting PTPN2-mediated dephosphorylation destabilizes c-MYC and suppresses acute myeloid leukemia survival}},
  author = {Wenbin Kuang and Dawei Wang and Mingge Song and Jianing Liu and Jiaxing Li and Wenmu Wang and Anyan Chen and Ya Chen and Jiayu Ding and Liping Wang and Wanjian Gu and Yibei Xiao and Xiao Wang and Peng Yang},
  journal = {Targetome},
  year = {2026},
  month = sep,
  doi = {10.48130/targetome-0026-0052},
  url = {https://doi.org/10.48130/targetome-0026-0052},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Targeting PTPN2-mediated dephosphorylation destabilizes c-MYC and suppresses acute myeloid leukemia survival
AU  - Wenbin Kuang
AU  - Dawei Wang
AU  - Mingge Song
AU  - Jianing Liu
AU  - Jiaxing Li
AU  - Wenmu Wang
AU  - Anyan Chen
AU  - Ya Chen
AU  - Jiayu Ding
AU  - Liping Wang
AU  - Wanjian Gu
AU  - Yibei Xiao
AU  - Xiao Wang
AU  - Peng Yang
PY  - 2026
DA  - 2026/09/01
JO  - Targetome
DO  - 10.48130/targetome-0026-0052
UR  - https://doi.org/10.48130/targetome-0026-0052
AB  - 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.
SN  - 3071-0596
SN  - 3070-3808
ER  -