Affiliation:
1. European Research Institute for Biology of Ageing (ERIBA) University Medical Center Groningen (UMCG) The Netherlands
2. Sanquin Research, Landsteiner Laboratory Sanquin Blood Supply Amsterdam The Netherlands
3. Department of Hematology, Amsterdam UMC University of Amsterdam The Netherlands
Abstract
Hematopoietic stem cell (HSC) fate decisions are dictated by epigenetic landscapes. The Polycomb Repressive Complex 1 (PRC1) represses genes that induce differentiation, thereby maintaining HSC self‐renewal. Depending on which chromobox (CBX) protein (CBX2, CBX4, CBX6, CBX7, or CBX8) is part of the PRC1 complex, HSC fate decisions differ. Here, we review how this occurs. We describe how CBX proteins dictate age‐related changes in HSCs and stimulate oncogenic HSC fate decisions, either as canonical PRC1 members or by alternative interactions, including non‐epigenetic regulation. CBX2, CBX7, and CBX8 enhance leukemia progression. To target, reprogram, and kill leukemic cells, we suggest and describe multiple therapeutic strategies to interfere with the epigenetic functions of oncogenic CBX proteins. Future studies should clarify to what extent the non‐epigenetic function of cytoplasmic CBX proteins is important for normal, aged, and leukemic blood cells.