Overexpression of CASP1 triggers acute promyelocytic leukemia cell pyroptosis and differentiation.

Xibao Yu, Xin Liu, Xuan Liu, Shuang Jin, Mengjun Zhong, Dingrui Nie, Xiangbo Zeng, Xianfeng Wang, Jiaxiong Tan, Yangqiu Li, Chengwu Zeng

European journal of pharmacology 2023 Apr 15

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Caspase-1 (CASP1)-mediated classical pyroptosis plays a key role in cancer development and management, however, the role of CASP1 and its regulation has not yet been documented for acute promyelocytic leukemia (APL). Here, we found that CASP1/GSDMD had lower expression in patients with APL and most other subtypes of primary de novo acute myeloid leukemia (AML) and was increased in all-trans-retinoic acid (ATRA)-treated APL cells. We showed that ATRA increases and activates CASP1 to trigger the pyroptosis and differentiation of APL cells. Mechanistically, ATRA could induce CASP1 expression via the IFNγ/STAT1 pathway in APL cells. In conclusion, ATRA-induced activation of CASP1 may serve as a suppressor in APL progression, as it triggers pyroptotic cell death and differentiation. Copyright © 2023 Elsevier B.V. All rights reserved.

Citation

Xibao Yu, Xin Liu, Xuan Liu, Shuang Jin, Mengjun Zhong, Dingrui Nie, Xiangbo Zeng, Xianfeng Wang, Jiaxiong Tan, Yangqiu Li, Chengwu Zeng. Overexpression of CASP1 triggers acute promyelocytic leukemia cell pyroptosis and differentiation. European journal of pharmacology. 2023 Apr 15;945:175614