Network-based analysis with primary cells reveals drug response landscape of acute myeloid leukemia

doi:10.1016/j.yexcr.2020.112054

	Network-based analysis with primary cells reveals drug response landscape of acute myeloid leukemia
	Chen, Cheng 2,3; Wang, Li 2,3,5; Li, Lili 4; Wang, Aoli 2,4,5; Huang, Tao 4,5; Hu, Jie 4,5; Zhao, Ming 4,5; Liu, Feiyang 2,4,5; Qi, Shuang 2,4,5; Hu, Chen 2,4,5
刊名	EXPERIMENTAL CELL RESEARCH
	2020-08-01
卷号	393
关键词	Acute myeloid leukemia (AML) Drug response Gene mutations
ISSN号	0014-4827
DOI	10.1016/j.yexcr.2020.112054
通讯作者	Xia, Ruixiang(xrx2041@163.com) ; Wang, Wenchao(wwcbox@hmfl.ac.cn) ; Liu, Qingsong(qsliu97@hmfl.ac.cn)
英文摘要	Acute myeloid leukemia (AML) is one of the most common, complex, and heterogeneous hematological malignancies in adults. Despite progresses in understanding the pathology of AML, the 5-year survival rates still remain low compared with CML, CLL, etc. The relationship between genomic features and drug responses is critical for precision medication. Herein, we depicted a picture for response of 145 drugs against 33 primary cell samples derived from AML patients with full spectrum of genomic features assessed by whole exon sequencing and RNA sequencing. In general, most of the samples were much more sensitive to the combinatorial chemotherapy regimens than the single chemotherapy drugs. Overall, these samples were moderately sensitive to the Traditional Chinese Medicine (TCM) and the targeted drugs. In the weighted gene coexpression network analysis (WGCNA), the TCM and targeted therapies displayed similar genetic signatures in the gene module correlation. Meanwhile, the expression of miRNAs, lncRNAs, and mRNAs did not display apparent gene module correlations among those different types of therapies. In addition, the combinatorial chemotherapy bear more module correlations than the single drugs. Interestingly, we found that the gene mutations and drug response were not enriched in any WGCNA module analysis. Most of the sensitive drug response biomarkers were enriched in the ribosome, endocytosis, cell cycle, and p53 associated signaling pathways. This study showed that gene expression modules might show better correlation than gene mutations for drug efficacy predictions.
资助项目	National Natural Science Foundation of China[81773777] ; National Natural Science Foundation of China[81673469] ; National Natural Science Foundation of China[81703007] ; Personalized Medicines-Molecular Signature-Based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020114] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program of China[2018ZX09711002] ; Natural Science Foundation of Anhui Province[1808085QH263] ; Natural Science Foundation of Anhui Province[1908085MH259] ; Higher Education Excellent Youth Foundation by Educational Commission of Anhui Province of China[gxyqZD2017029] ; Key Research and Development Project of Anhui Province[201904a07020057] ; China Postdoctoral Science Foundation[2019M652057] ; Frontier Science Key Research Program of CAS[QYZDB-SSWSLH037] ; CASHIPS Director's Fund[BJPY2019A03] ; Key Program of 13th five-year plan of CASHIPS[KP-201726] ; Presidential Foundation of CASHIPS[YZJJ2018QN17] ; High Magnetic Field Laboratory of Anhui Province
WOS关键词	ADVANCEMENTS ; EXPRESSION
WOS研究方向	Oncology ; Cell Biology
语种	英语
出版者	ELSEVIER INC
WOS记录号	WOS:000539427300004
资助机构	National Natural Science Foundation of China ; Personalized Medicines-Molecular Signature-Based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program of China ; Natural Science Foundation of Anhui Province ; Higher Education Excellent Youth Foundation by Educational Commission of Anhui Province of China ; Key Research and Development Project of Anhui Province ; China Postdoctoral Science Foundation ; Frontier Science Key Research Program of CAS ; CASHIPS Director's Fund ; Key Program of 13th five-year plan of CASHIPS ; Presidential Foundation of CASHIPS ; High Magnetic Field Laboratory of Anhui Province
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/103019]
专题	中国科学院合肥物质科学研究院
通讯作者	Xia, Ruixiang; Wang, Wenchao; Liu, Qingsong
作者单位	1.Anhui Univ, Inst Phys Sci & Informat Technol, Hefei 230601, Anhui, Peoples R China 2.Chinese Acad Sci, Hefei Inst Phys Sci, High Magnet Field Lab, Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei 230031, Anhui, Peoples R China 3.Univ Sci & Technol China, Hefei 230036, Anhui, Peoples R China 4.Precis Med Res Lab Anhui Prov, Hefei 230088, Anhui, Peoples R China 5.Chinese Acad Sci, Precis Targeted Therapy Discovery Ctr, Inst Technol Innovat, Hefei Inst Phys Sci, Hefei 230088, Anhui, Peoples R China 6.Anhui Med Univ, Dept Hematol, Affiliated Hosp 1, Hefei 230022, Anhui, Peoples R China
推荐引用方式 GB/T 7714	Chen, Cheng,Wang, Li,Li, Lili,et al. Network-based analysis with primary cells reveals drug response landscape of acute myeloid leukemia[J]. EXPERIMENTAL CELL RESEARCH,2020,393.
APA	Chen, Cheng.,Wang, Li.,Li, Lili.,Wang, Aoli.,Huang, Tao.,...&Liu, Qingsong.(2020).Network-based analysis with primary cells reveals drug response landscape of acute myeloid leukemia.EXPERIMENTAL CELL RESEARCH,393.
MLA	Chen, Cheng,et al."Network-based analysis with primary cells reveals drug response landscape of acute myeloid leukemia".EXPERIMENTAL CELL RESEARCH 393(2020).