An essential role for NF-kappa B 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 var iety of cell types. However, a role for NF-kappa B in human CD34(+) bone ma rrow cells has not been described. We provide evidence here that virtually all human CD34(+) bone marrow cells express NF-kappa B that can be activate d by exposure to phorbol 12-myristate 13-acetate and a variety of cytokines , eg, tumor necrosis factor alpha, interleukin-3, and granulocyte-macrophag e colony-stimulating factor. In addition, we demonstrate that NF-KB may be required for human CD34(+) bone marrow cell clonogenic function and surviva l, These results offer insight into a new role for NF-kappa B in maintainin g survival and function in hematopoietic stem and progenitor cells and sugg est 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.