1. Academic Validation
  2. Network-based analysis with primary cells reveals drug response landscape of acute myeloid leukemia

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

  • Exp Cell Res. 2020 Aug 1;393(1):112054. doi: 10.1016/j.yexcr.2020.112054.
Cheng Chen 1 Li Wang 2 Lili Li 3 Aoli Wang 4 Tao Huang 5 Jie Hu 5 Ming Zhao 5 Feiyang Liu 4 Shuang Qi 4 Chen Hu 4 Wenliang Wang 1 Jing Liu 4 Jian Ge 3 Ruixiang Xia 6 Wenchao Wang 7 Qingsong Liu 8
Affiliations

Affiliations

  • 1 High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, PR China; University of Science and Technology of China, Hefei, Anhui, 230036, PR China.
  • 2 High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, PR China; University of Science and Technology of China, Hefei, Anhui, 230036, PR China; Precision Targeted Therapy Discovery Center, Institute of Technology Innovation, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230088, PR China.
  • 3 Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, PR China.
  • 4 High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, PR China; Precision Medicine Research Laboratory of Anhui Province, Hefei, Anhui, 230088, PR China; Precision Targeted Therapy Discovery Center, Institute of Technology Innovation, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230088, PR China.
  • 5 Precision Medicine Research Laboratory of Anhui Province, Hefei, Anhui, 230088, PR China; Precision Targeted Therapy Discovery Center, Institute of Technology Innovation, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230088, PR China.
  • 6 Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, PR China. Electronic address: [email protected]
  • 7 High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, PR China; Precision Medicine Research Laboratory of Anhui Province, Hefei, Anhui, 230088, PR China; Precision Targeted Therapy Discovery Center, Institute of Technology Innovation, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230088, PR China. Electronic address: [email protected]
  • 8 High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, PR China; University of Science and Technology of China, Hefei, Anhui, 230036, PR China; Precision Medicine Research Laboratory of Anhui Province, Hefei, Anhui, 230088, PR China; Precision Targeted Therapy Discovery Center, Institute of Technology Innovation, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230088, PR China; Institute of Physical Science and Information Technology, Anhui University, Hefei, Anhui, 230601, PR China. Electronic address: [email protected]
Abstract

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.

Keywords

Acute myeloid leukemia (AML); Drug response; Gene mutations.

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