Identification of mast cells as a candidate significant target of immunotherapy for acute myeloid leukemia

Hematology. 2021 Dec;26(1):284-294. doi: 10.1080/16078454.2021.1889158.

Abstract

Objection: Immunotherapy based on T cells is a new therapy for Acute myeloid leukemia (AML). However, there has not been considerable improvement compared with traditional chemotherapeutics. This study aimed to identify important immune cells, genes, and drugs associated with the immunotherapy of AML.

Methods: The gene expression profile and clinical data of patients with AML were downloaded from TCGA database, and the abundance ratio of immune cells was obtained via CIBERSORT. Kaplan-Meier (KM) survival analysis was used to assess the relationship between immune cells and survival time of patients with AML. Differentially expressed genes (DEGs) analysis was conducted to obtained DEGs related to mast cells. Then, protein-protein interaction (PPI) analysis and enrichment analysis were performed to explore the hub genes. Finally, Connectivity Map (CMap) database was utilized to predicts potential drugs that may reverse or induce the mast cell-related gene expression.

Results: Our study showed that mast cell was correlated with survival time of patients with AML, and 135 genes were screened to be related with mast cells. 6 hub genes were identified via PPI network, and 3 potential small molecule drugs were screened to be related to regulating the mast cell-related gene expression via CMap database.

Conclusion: The hub genes and drugs have high research value and clinical application in AML therapy. Our study not only provides gene targets and small molecule drugs for AML immunotherapy concerning mast cells but also provides new ideas for researchers to explore immunotherapy targets of other tumors.

Keywords: Acute myeloid leukemia; bioinformatics; immunotherapy; mast cells.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Drug Discovery
  • Gene Expression Profiling
  • Humans
  • Immunotherapy
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / immunology
  • Mast Cells / drug effects*
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Molecular Targeted Therapy
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Transcriptome / drug effects

Substances

  • Antineoplastic Agents
  • Small Molecule Libraries