An essential role for NF-κB in human CD34+ bone marrow cell survival

The transcription factor, NF-kappa B, is important for T-cell activation, B-cell maturation, and human immunodeficiency virus transcription and plays a role in alternatively mediating and protecting against apoptosis in a variety of cell types. However, a role for NF-kappa B in human CD34(+) bone marrow cells has not been described. We provide evidence here that virtually all human CD34(+) bone marrow cells express NF-kappa B that can be activated by exposure to phorbol 12-myristate 13-acetate and a variety of cytokines, eg, tumor necrosis factor alpha, interleukin-3, and granulocyte-macrophage colony-stimulating factor. In addition, we demonstrate that NF-KB may be required for human CD34(+) bone marrow cell clonogenic function and survival, These results offer insight into a new role for NF-kappa B in maintaining survival and function in hematopoietic stem and progenitor cells and suggest that proposed strategies involving inhibition of NF-kappa B activation as an adjunct to cancer chemotherapy should be approached with caution. (C) 1999 by The American Society of Hematology.