Bone marrow infiltrated natural killer cells predicted the anti-leukemia activity of MCL1 or BCL2 inhibitors in acute myeloid leukemia

被引:16
作者
Dai, Yu-Jun [1 ,2 ]
He, Si-Yuan [3 ]
Hu, Fang [1 ,2 ]
Li, Xue-Ping [1 ,2 ]
Zhang, Jian-Ming [4 ]
Chen, Si-Liang [5 ]
Zhang, Wei-Na [6 ]
Sun, Hai-Min [7 ,8 ]
Wang, Da-Wei [4 ,7 ]
机构
[1] Sun Yat Sen Univ, Dept Hematol Oncol, Canc Ctr, Guangzhou 500020, Peoples R China
[2] Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, 651 Dongfeng East Rd, Guangzhou 500020, Peoples R China
[3] Univ Texas MD Anderson Canc Ctr, UTHlth Grad Sch Biomed Sci, Houston, TX 77030 USA
[4] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Natl Res Ctr Translat Med, Shanghai 200025, Peoples R China
[5] Peking Univ, Dept Hematol, Shenzhen Hosp, Shenzhen 518036, Peoples R China
[6] Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Hematol, Guangzhou 510623, Peoples R China
[7] Shanghai Jiao Tong Univ, Shanghai Inst Hematol, State Key Lab Med Genom, Ruijin Hosp,Sch Med, Shanghai 200025, Peoples R China
[8] Shanghai Jiao Tong Univ, Rui Jin Hosp North, Dept Hematol, Sch Med, Shanghai 201800, Peoples R China
基金
上海市自然科学基金; 中国国家自然科学基金;
关键词
NK cells; MCL1; inhibitor; BCL2; AML; Immunotherapy; NK CELLS;
D O I
10.1186/s12943-020-01302-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Acute myeloid leukemia (AML) is still incurable due to its heterogeneity and complexity of tumor microenvironment. It is imperative therefore to understand the molecular pathogenesis of AML and identify leukemia-associated biomarkers to formulate effective treatment strategies. Here, we systematically analyzed the clinical characters and natural killer (NK) cells portion in seventy newly-diagnosis (ND) AML patients. We found that the proportion of NK cells in the bone marrow of ND-AML patients could predict the prognosis of patients by analyzing the types and expression abundance of NK related ligands in tumor cells. Furthermore, MCL1 inhibitor but not BCL2 inhibitor combined with NK cell-based immunotherapy could effectively improve the therapeutic efficiency via inhibiting proliferation and inducing apoptosis of AML primary cells as well as cell lines in vitro. There results provide valuable insights that could help for exploring new therapeutic strategies for leukemia treatment.
引用
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页数:7
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