An essential role for NF-kappaB in human CD34(+) bone marrow cell survival.
The transcription factor, NF-kappaB, 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-kappaB in human CD34(+) bone marrow cells has not been described. We provide evidence here that virtually all human CD34(+) bone marrow cells express NF-kappaB 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-kappaB may be required for human CD34(+) bone marrow cell clonogenic function and survival. These results offer insight into a new role for NF-kappaB in maintaining survival and function in hematopoietic stem and progenitor cells and suggest that proposed strategies involving inhibition of NF-kappaB activation as an adjunct to cancer chemotherapy should be approached with caution.
Pyatt
D W
DW
The Molecular Toxicology and Environmental Health Sciences Center, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO, USA.
Stillman
W S
WS
Yang
Y
Y
Gross
S
S
Zheng
J H
JH
Irons
R D
RD
D000328:Adult; D015703:Antigens, CD; D018941:Antigens, CD19; D018952:Antigens, CD34; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D002469:Cell Separation; D002470:Cell Survival; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; D018941:Antigens, CD19; D018952:Antigens, CD34; D016207:Cytokines; D016328:NF-kappa B; D013755:Tetradecanoylphorbol Acetate