NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemia.

Jan 13, 2025

Experts: Qing Zhu,Jia Cheng,Yuqing Gao,Zimu Zhang,Jian Pan,Xin Su,Danhong Fei,Linbo Cai,Juanjuan Yu,Yanling Chen,Wanyan Jiao,Di Wu,Xiaolu Li,Peifang Xiao

Cell cycle dysregulation and the corresponding metabolic reprogramming play significant roles in tumor development and progression. CDK9, a kinase that regulates gene transcription and cell cycle, also induces oncogene transcription and abnormal cell cycle in AML cells. The function of CDK9 for gene regulation in AML cells requires further exploration. In this study, we knocked down the CDK9 to investigate its effects on the growth and survival of AML cells. Through RNA-seq analysis, we identified that in U937 cells CDK9 regulates numerous genes involved in proliferation and apoptosis, including mTOR, SREBF1, and Bcl-2. Furthermore, our results demonstrated that both CDK9 and FASN are crucial for the proliferation and survival of Kasumi-1 and U937 cells. Mechanistically, MCL1, c-Myc, and Akt/mTOR/SREBF1 may be critical factors and pathways in the combined therapy of NVP-2 and Orlistat. In summary, our study revealed that CDK9 and FASN are vital for maintaining AML cell survival and proliferation. Treatment with NVP-2 and Orlistat may be a promising clinical candidate for patients with AML.

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ABOUT THE EXPERTS

Qing Zhu,Jia Cheng,Yuqing Gao,Zimu Zhang,Jian Pan,Xin Su,Danhong Fei,Linbo Cai,Juanjuan Yu,Yanling Chen,Wanyan Jiao,Di Wu,Xiaolu Li,Peifang Xiao

Qing Zhu

Children’s Hospital of Soochow University, Suzhou, China.

Department of Pediatrics, The Third People’s Hospital of Kunshan, Suzhou, China.

Jia Cheng

Children’s Hospital of Soochow University, Suzhou, China.

Yuqing Gao

Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, China.

Zimu Zhang

Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, China.

Jian Pan

Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, China.

Xin Su

Department of Hematology, Children’s Hospital of Soochow University, Suzhou, China.

Danhong Fei

Children’s Hospital of Soochow University, Suzhou, China.

Department of Pediatrics, Municipal Hospital Affiliated to Taizhou University, Taizhou, China.

Linbo Cai

Children’s Hospital of Soochow University, Suzhou, China.

Juanjuan Yu

Children’s Hospital of Soochow University, Suzhou, China.

Yanling Chen

Children’s Hospital of Soochow University, Suzhou, China.

Wanyan Jiao

Children’s Hospital of Soochow University, Suzhou, China.

Department of Pediatrics, The Third People’s Hospital of Yancheng, Yancheng, China.

Di Wu

Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, China.

Xiaolu Li

Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, China.

Peifang Xiao

Department of Hematology, Children’s Hospital of Soochow University, Suzhou, China.