Apoptosis-Related Gene Expression Profiling in Hematopoietic Cell Fractions of MDS Patients

PLoS One. 2016 Nov 30;11(11):e0165582. doi: 10.1371/journal.pone.0165582. eCollection 2016.

Abstract

Although the vast majority of patients with a myelodysplastic syndrome (MDS) suffer from cytopenias, the bone marrow is usually normocellular or hypercellular. Apoptosis of hematopoietic cells in the bone marrow has been implicated in this phenomenon. However, in MDS it remains only partially elucidated which genes are involved in this process and which hematopoietic cells are mainly affected. We employed sensitive real-time PCR technology to study 93 apoptosis-related genes and gene families in sorted immature CD34+ and the differentiating erythroid (CD71+) and monomyeloid (CD13/33+) bone marrow cells. Unsupervised cluster analysis of the expression signature readily distinguished the different cellular bone marrow fractions (CD34+, CD71+ and CD13/33+) from each other, but did not discriminate patients from healthy controls. When individual genes were regarded, several were found to be differentially expressed between patients and controls. Particularly, strong over-expression of BIK (BCL2-interacting killer) was observed in erythroid progenitor cells of low- and high-risk MDS patients (both p = 0.001) and TNFRSF4 (tumor necrosis factor receptor superfamily 4) was down-regulated in immature hematopoietic cells (p = 0.0023) of low-risk MDS patients compared to healthy bone marrow.

MeSH terms

  • Apoptosis Regulatory Proteins / genetics*
  • Case-Control Studies
  • Cells, Cultured
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / pathology

Substances

  • Apoptosis Regulatory Proteins

Grants and funding

This work was supported by grants from the "Dutch Organization for Scientific Research" (NWO, 92003420) to SMCL and the "Dutch Cancer Society" (KWF) to NM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.