Increased expression of HERG K+ channels contributes to myelodysplastic syndrome progression and displays correlation with prognosis stratification

Hematology. 2016 Dec;21(10):583-592. doi: 10.1080/10245332.2016.1151603. Epub 2016 Mar 16.

Abstract

Objectives: Human ether-a-go-go-related gene (HERG) K+ channels are shown to be aberrantly expressed in a variety of cancer cells where they play roles in contributing to cancer progression. Myelodysplastic syndromes (MDS) are a group of clinical heterogeneous disorders characterized by bone marrow failure and dysplasia of blood cells. However, the involvement of HERG K+ channels in MDS development is poorly understood.

Methods: The expression of HERG K+ channels in untreated MDS, acute myeloid leukemia (AML) patients and the control group was detected by flow cytometry. The roles of HERG K+ channels in regulation of SKM-1 cell proliferation, apoptosis, and cell cycle were determined by CCK-8 assay and flow cytometry, respectively.

Results: We found that expression of HERG K+ channels in MDS patients was significantly higher than controls and was lower than AML. Percentage of HERG K+ channels on CD34+CD38- cells gradually increased from controls to high-grade MDS subtypes. And HERG K+ channel levels showed an ascending tendency from low-risk to high-risk MDS group. In addition, the CCK-8 assay, apoptosis and cell cycle analysis were performed and showed that blockage of HERG K+ channels decreased the proliferation of MDS cells but rarely had effects on cell apoptosis and cell cycle distribution.

Conclusion: Our study demonstrated that HERG K+ channels might be a potential tumor marker of MDS. These channels were likely to contribute to MDS progression and were helpful for predicting prognosis of MDS. Inhibition of HERG K+ channels might be a novel therapeutic measure for MDS.

Keywords: CD34+CD38− cells; HERG K+ channels; Myelodysplastic syndromes; Tumor marker.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apoptosis / physiology
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Cell Cycle / physiology
  • Cell Proliferation / physiology
  • Child
  • ERG1 Potassium Channel / biosynthesis*
  • ERG1 Potassium Channel / genetics
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / genetics
  • Myelodysplastic Syndromes / metabolism*
  • Myelodysplastic Syndromes / pathology
  • Prognosis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • ERG1 Potassium Channel
  • KCNH2 protein, human