[Frontiers in Bioscience 14, 2358-2371, January 1, 2009]

Various functions of caspases in hematopoiesis

Nathalie Droin1,2, Arnaud Jacquel1,2,, Leslie Guery1,2,, Erick Dufour1,2,, Carmen Garrido1,2,, Eric Solary1,2,3

1Inserm, UMR 866, Dijon, F-21079 France, 2University of Burgundy, Faculty of Medicine, 7 boulevard Jeanne d'Arc, Dijon, F-21079 France, 3CHU Le Bocage, BP1542, Dijon, F-21034 Dijon cedex, France

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Structure and classification of caspases
4. Caspase-dependent apoptosis
5. Caspases, hematopoietic stem cells and early progenitors
6. Caspases and bone marrow microenvironment
7. Caspases in platelet formation
8. Caspases in platelet life span
9. Caspases in erythroid differentiation
10. Caspases in erythroid cell life span
11. Caspases and monocyte differentiation into macrophages
12. Caspases in neutrophil life span
13. Caspases in eosinophil life span
14. Caspases in mast cell life span
15. Caspases and lymphocyte death or proliferation
16. Conclusions
17. Acknowledgement
18. References

1. ABSTRACT

The role of cysteine proteases of the caspase family in apoptosis is well defined. Some caspases were initially shown to be involved in cytokine maturation along inflammatory response. In the recent years, several other non apoptotic functions of caspases were identified. In hematopoietic cells, caspases play a role in specific pathways of differentiation (erythropoiesis, differentiation of monocytes into macrophages, formation of proplatelets by megakaryocytes). These enzymes also play a non-apoptotic and complex role in regulating the maturation and proliferation of specific lymphocytes. Lastly, the apoptotic functions of caspases regulate the life span of several but not all blood cell types. The present review summarizes the current knowledge in these different functions. We show that the nature of involved enzymes, the pathways leading to their activation and the specificity of their cellular target proteins varies strongly from a cell type to another. We indicate also that, in most situations, specific Bcl-2-related proteins are involved in the control of caspase activation. Lastly, we discuss the deregulation of these pathways in hematopoietic diseases, including those in which an excess in caspase activation leads to cell death and those in which a default in caspase activation could block cell differentiation.