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Blood, Vol. 93 No. 10 (May 15), 1999:
pp. 3302-3308
An Essential Role for NF- B in Human CD34+ Bone Marrow
Cell Survival
David W. Pyatt,
Wayne S. Stillman,
Yanzhu Yang,
Sherilyn Gross,
Jia hua Zheng, and
Richard D. Irons
From The Molecular Toxicology and Environmental Health Sciences
Center, School of Pharmacy, the Department of Pathology, School of
Medicine, and the Cancer Center, University of Colorado Health Sciences
Center, Denver, CO.
The transcription factor, NF- 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-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-B that can be
activated by exposure to phorbol 12-myristate 13-acetate and a variety
of cytokines, eg, tumor necrosis factor  , interleukin-3, and
granulocyte-macrophage colony-stimulating factor. In addition, we
demonstrate that NF-B may be required for human CD34+
bone marrow cell clonogenic function and survival. These results offer
insight into a new role for NF-B in maintaining survival and
function in hematopoietic stem and progenitor cells and suggest that
proposed strategies involving inhibition of NF-B activation as an
adjunct to cancer chemotherapy should be approached with caution.
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