NK-cell dysfunction of acute myeloid leukemia in relation to the renin-angiotensin system and neurotransmitter genes

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TÜRK S., Baesmat A. S., YILMAZ A., TÜRK C., MALKAN Ü. Y., UÇAR G., ...Daha Fazla

OPEN MEDICINE, cilt.17, sa.1, ss.1495-1506, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 17 Sayı: 1
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1515/med-2022-0551
  • Dergi Adı: OPEN MEDICINE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1495-1506
  • Anahtar Kelimeler: leukemia, natural killer cells, dysfunction, NATURAL-KILLER-CELLS, HUMAN T-CELLS, RECEPTOR, CYTOTOXICITY, INFLAMMATION, EXPRESSION, IMMUNITY, GROWTH
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Acute myeloid leukemia (AML) is the most heterogeneous hematological disorder and blast cells need to fight against immune system. Natural killer (NK) cells can elicit fast anti-tumor responses in response to surface receptors of tumor cells. NK-cell activity is often impaired in the disease, and there is a risk of insufficient tumor suppression and progression. The aim of this study is to assess the dysfunction of NK cells in AML patients via focusing on two important pathways. We obtained single-cell RNA-sequencing data from NK cells obtained from healthy donors and AML patients. The data were used to perform a wide variety of approaches, including DESeq2 (version 3.9), limma (version 3.26.8) power differential expression analyses, hierarchical clustering, gene set enrichment, and pathway analysis. ATP6AP2, LNPEP, PREP, IGF2R, CTSA, and THOP1 genes were found to be related to the renin-angiotensin system (RAS) family, while DPP3, GLRA3, CRCP, CHRNA5, CHRNE, and CHRNB1 genes were associated with the neurotransmitter pathways. The determined genes are expressed within different patterns in the AML and healthy groups. The relevant molecular pathways and clusters of genes were identified, as well. The cross-talks of NK-cell dysfunction in relation to the RAS and neurotransmitters seem to be important in the genesis of AML.