Clinical implication and potential function of ARHGEF6 in acute myeloid leukemia: An in vitro study

PLoS One. 2023 Apr 7;18(4):e0283934. doi: 10.1371/journal.pone.0283934. eCollection 2023.

Abstract

The roles of Rho GTPases in various types of cancer have been extensively studied, but the research of Rho guanine nucleotide exchange factors (GEFs) in cancer is not comprehensive. Rho guanine nucleotide exchange factor 6 (ARHGEF6) is an important member of the Rho GEFs family involved in cytoskeletal rearrangement, and it has not been investigated in acute myeloid leukemia (AML). Our research showed that the expression of ARHGEF6 was mainly higher in AML cell lines, meanwhile, was highest in the samples from patients with AML compared to other cancer types. High ARHGEF6 expression in AML was associated with a good prognosis. ARHGEF6low cases showed significantly higher overall survival (OS) after autologous or allogeneic HSCT (auto/allo-HSCT). High expression of ARHGEF6 downregulates the negative regulation of myeloid differentiation process and upregulates G protein-coupled receptor signaling pathway-related processes, among which HOXA9, HOXB6, and TRH have significant differential expression and prognostic impact in AML. Therefore, ARHGEF6 can become a prognostic marker in AML; ARHGEF6low patients can gain from auto/allo-HSCT.

MeSH terms

  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Prognosis
  • Research Design
  • Retrospective Studies
  • Rho Guanine Nucleotide Exchange Factors* / genetics
  • Signal Transduction

Substances

  • Rho Guanine Nucleotide Exchange Factors
  • ARHGEF6 protein, human

Grants and funding

This work was supported by Guangdong Basic and Applied Basic Research Foundation (2020A1515110581 to J. Zhou), Science and Technology Program of Guangzhou (202201020209 to J. Zhou), start-up funds from Guangzhou University to J. Zhou, Chinese National Science Foundation (32071145 and 31771572 to B. Xue), the Nature Science Foundation of Jiangsu Province (BK20191356 to B. Xue). There was no additional external funding received for this study.