Calsyntenin-2 promotes the pathology of acute myeloid leukemia via activation of the JAK2-STAT3 signaling pathway.

Authors

Yuting Dou, Xu Cao, Ke Ji, Manman Hu, Shuang Zhu, Shulin Luo, Qingyang Pei, Kexin Zeng, Jiang Cao, Feng Li, Qingyun Wu

Published in

Cellular signalling. Pages 112960. Oct 25, 2026. Epub Oct 25, 2026.

Abstract

Although considerable progress has been made in the treatment of acute myeloid leukemia (AML), therapeutic outcomes remain unsatisfactory. Thus, it is of great important to investigate the leukemiagenesis mechanism of AML. Previous studies indicated that Calsyntenin-2 (CLSTN2) was closely associated with the progression of AML, however, roles and mechanisms of CLSTN2 in the pathology of AML remain unclear.
In this study, series of methods including gene overexpression and knockdown, RT-qPCR, Western blot, CCK-8 assay, flow cytometry, colony formation assay, and RNA-sequencing was used to investigate roles and mechanisms of CLSTN2 in the biological behaviors of AML cell lines both in the in vivo and invitro experiments levels.
CLSTN2 was high expressed in AML and predicts a poor prognosis. Knockdown the expression of CLSTN2 inhibited AML cell viability and clonogenic capacity, induced cell apoptosis, and caused G0/G1 phase arrest, whereas CLSTN2 overexpression displayed opposite results. Moreover, knockdown CLSTN2 reduced AML cells' infiltration, delayed disease progression, and prolonged the survival of xenograft mice, while CLSTN2 overexpression showed opposite results. MLL-AF9 induced AML mouse models results also verfied that CLSTN2 knockout inhibited the progression of AML. Mechanistically, CLSTN2 interacted with STAT3 and activated JAK2-STAT3 pathway to promote the pathology of AML, the STAT3 degrader SD-36 treatment could partially reverse CLSTN2 overexpression caused cell cycle acceleration, enhanced cell viability, colony formation ability and anti-apoptotic phenotype.
CLSTN2 promoted cell proliferation, inhibited cell apoptosis, and accelerated the pathology of AML by interacting with STAT3 which led to the hyper-activation of JAK2-STAT3 signaling pathway. These results suggested that CLSTN2 might be a potential therapeutic target for AML.

PMID:
42927818
Bibliographic data and abstract were imported from PubMed on 26 Oct 2026.

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