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Apoptosis and C/EPBε in Mice Myeloid Cells

C/EBPε −/− mice: increased rate of myeloid proliferation and apoptosis

Leukemia volume 15, pages 103–111 (2001)Cite this article

Abstract

CCAAT/enhancer binding protein epsilon (C/EBPε) is essential for terminal granulocytic differentiation. Its expression begins at the transition between the proliferative and non-proliferative compartments of myelopoiesis. We studied the effect of targeted disruption of the C/EBPε gene on murine myeloid proliferation and apoptosis. Bone marrow cellularity of C/EBPε −/− and wild-type mice was 95% and 65%, respectively. The C/EBPε −/− mice had an expansion in the number of their CFU-GM/femur. The number of myeloid committed progenitor cells in the peripheral blood and the spleen of these mice was also increased. Bromodeoxyuridine (BrDU) pulse labeling studies demonstrated that the fraction of actively proliferating cells was two-fold higher in the bone marrow of C/EBPε −/− mice. However, the number of myeloid colonies arising from purified Sca-1+/lin− early hematopoietic progenitor cells and from bone marrow mononuclear cells grown in different cytokine combinations was not significantly different between wild-type and knock-out mice. Also, long-term marrow growth, and CFU were not different between the wild-type and C/EBPε −/− mice. The sensitivity to induction of apoptosis in the committed progenitor cell compartment after either withdrawal of growth factor or brief exposure to etoposide was normal. However, Gr-1 antigen-positive C/EBPε −/− granulocytic cells showed an increased rate of apoptosis in comparison to their wild-type counterparts. In summary, the myeloid compartment appears to be expanded in mice lacking C/EBPε. However, this is not the consequence of an intrinsic myeloproliferation but due to an indirect, possibly cytokine-mediated stimulation of myelopoiesis in vivo. C/EBPε may have a role in the inhibition of apoptosis in maturing granulocytic cells.

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Acknowledgements

This work was in part supported by the following NIH grants: NIH Genetic Core, Lymphoma Foundation of America, Parker Hughes Fund and C and H Koeffler Grant. Walter Verbeek was supported by a Grant of the Deutsche Forschungsgemeinschaft.

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  1. Division of Hematology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA

    W Verbeek, M Wächter, J Lekstrom-Himes & HP Koeffler

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Verbeek, W., Wächter, M., Lekstrom-Himes, J. et al. C/EBPε −/− mice: increased rate of myeloid proliferation and apoptosis. Leukemia 15, 103–111 (2001). https://doi.org/10.1038/sj.leu.2401995

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