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.