Boanmycin induces apoptosis and overcomes venetoclax resistance in acute myeloid leukemia

Author:

Wang Jin-Xing123,Zhang Peng-Wei2,Yuan Luo-Wei4,Jiang Jian2,Cheng Xiao-Hui2,Li Ju-Heng2,Tang Mei-Qin2,Fan Jiao-Yang2,Zhu Wei3,Lei Yong4,Tian Fa-Qing2

Affiliation:

1. Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School , Shenzhen , China

2. Department of Hematology , The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen , Shenzhen , China

3. Department of Pathology Technique , Guangdong Medical University , Dongguan , Guangdong Province , China

4. School of Medicine, The Chinese University of Hong Kong , Shenzhen , Guangdong , China

Abstract

Abstract Objectives This study aimed to investigate the efficacy of boanmycin, a clinical drug used for head and neck cancers, in the treatment of acute myeloid leukemia (AML), particularly in venetoclax-resistant AML cells. Methods The cell viability assay was conducted to measure the inhibitory effects of boanmycin on the AML cell lines and patient primary cells using the CCK8 reagent. The colony formation assay was performed to evaluate the colony formation ability of HL60 and venetoclax-resistant HL60 (HL60-res) cells with or without boanmycin treatment. Flow cytometry was performed to detect cell apoptosis level, and Western blot was used to assess changes in apoptosis-related proteins. Results Our findings reveal that boanmycin significantly inhibits AML cell proliferation and colony formation, and induces apoptosis. Importantly, boanmycin exhibits substantial inhibitory effects on venetoclax-resistant cells, and suppresses the proliferation of peripheral blood mononuclear cells (PBMCs) or bone marrow mononuclear cells (BMMCs) derived from newly diagnosed and relapsed AML patients. Conclusions Boanmycin may overcome venetoclax resistance and offer therapeutic benefits for patients with venetoclax-resistant AML.

Funder

Natural Science Foundation of Shenzhen Municipality

Special Fund Project for Economic and Technological Development of Longgang District, Shenzhen

School and Hospital Joint Fund of the Second Affiliated Hospital of Chinese University of Hong Kong, Shenzhen

National Natural Science Foundation of China

Pearl River Talent Program

Natural Science Foundation of Guangdong Province

Publisher

Walter de Gruyter GmbH

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