Polycomb group proteins in hematopoietic stem cell aging and malignancies

Abstract

Protection of the transcriptional “stemness” network is important to maintain a healthy hematopoietic stem cells (HSCs) compartment during the lifetime of the organism. Recent evidence shows that fundamental changes in the epigenetic status of HSCs might be one of the driving forces behind many age-related HSC changes and might pave the way for HSC malignant transformation and subsequent leukemia development, the incidence of which increases exponentially with age. Polycomb group (PcG) proteins are key epigenetic regulators of HSC cellular fate decisions and are often found to be misregulated in human hematopoietic malignancies. In this review, we speculate that PcG proteins balance HSC aging against the risk of developing cancer, since a disturbance in PcG genes and proteins affects several important cellular processes such as cell fate decisions, senescence, apoptosis, and DNA damage repair.

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Acknowledgments

We thank Dr. Leonid Bystrykh for inspiring discussions and critical reading of the manuscript. This work was supported by the Netherlands Organization for Scientific Research (VICI 918-76-601).

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Correspondence to Gerald de Haan.

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Klauke, K., de Haan, G. Polycomb group proteins in hematopoietic stem cell aging and malignancies. Int J Hematol 94, 11–23 (2011). https://doi.org/10.1007/s12185-011-0857-0

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Keywords

  • Hematopoietic stem cells
  • Aging
  • Leukemia
  • Epigenetics
  • Polycomb