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Lentiviral-mediated Knockdown During Ex Vivo Erythropoiesis of Human Hematopoietic Stem Cells
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CAR virus receptor mediates erythroid differentiation and migration and is downregulated in MDS

Karin Bauer1,2, Sigrid Machherndl-Spandl3,4, Lukas Kazianka1

  • 1Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.

Leukemia
|September 6, 2023
PubMed

Insights

Coxsackie-Adenovirus receptor (CAR) is downregulated in myelodysplastic syndromes (MDS). Decreased CAR expression in erythroid progenitor cells correlates with high-risk MDS and poor survival, impacting disease progression.

Area of Science:

  • Hematology
  • Molecular Biology
  • Oncology

Background:

  • Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by bone marrow dysplasia and peripheral cytopenia, often leading to anemia.
  • Erythroid progenitor cells (EP) are critical in red blood cell development, and their dysfunction contributes to MDS pathogenesis.

Purpose of the Study:

  • To identify genes abnormally expressed in MDS erythroid progenitor cells (EP) that contribute to disease development.
  • To investigate the role of the Coxsackie-Adenovirus receptor (CAR/CXADR) in MDS pathogenesis and its prognostic significance.

Main Methods:

  • Screening of gene expression in CD45low/CD105+ EP from MDS patients and controls.
  • Lentiviral transduction of CXADR in erythroblast cell lines (HEL, K562, KU812).
  • Conditional knockout of Cxadr in C57BL/6 mice to assess in vivo effects.

Main Results:

  • Coxsackie-Adenovirus receptor (CAR/CXADR) was significantly downregulated in EP from MDS patients.
  • CXADR re-expression in cell lines increased early erythroid antigen expression (CD36, CD71, glycophorin A) and cell migration.
  • Cxadr knockout in mice induced anemia and erythroid dysplasia.
  • Decreased CAR expression on EP correlated with high-risk MDS and reduced patient survival.

Conclusions:

  • CAR is a functionally relevant marker downregulated in MDS EP, contributing to maturation defects and altered migration.
  • Reduced CAR expression is of prognostic significance in MDS, potentially indicating higher risk and poorer survival.
  • CAR may play a crucial role in the pathological accumulation of EP in the bone marrow in MDS.

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