Document Detail


Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1alpha.
MedLine Citation:
PMID:  15860672     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We examined expression of B cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) and a proliferation-inducing ligand (APRIL) on chronic lymphocytic leukemia (CLL) B cells and nurselike cells (NLCs), which differentiate from CD14+ cells when cultured with CLL B cells. NLCs expressed significantly higher levels of APRIL than monocytes and significantly higher levels of BAFF and APRIL than CLL B cells. Also, the viability of CLL B cells cultured with NLCs was significantly reduced when CLL B cells were cultured with decoy receptor of B-cell maturation antigen (BCMA), which can bind both BAFF and APRIL, but not with BAFF receptor:Fc (BAFF-R:Fc), which binds only to BAFF. The effect(s) of BAFF or APRIL on leukemia cell survival appeared additive and distinct from that of stromal cell-derived factor-1alpha (SDF-1alpha), which in contrast to BAFF or APRIL induced leukemia cell phosphorylation of p44/42 mitogen-activated protein kinase (extracellular signal-regulated kinase-1/2 [ERK1/2]) and AKT. Conversely, BAFF and APRIL, but not SDF-1alpha, induced CLL-cell activation of the nuclear factor-kappaB1 (NF-kappaB1) and enhanced CLL-cell expression of the antiapoptotic protein Mcl-1. However, BAFF, but not APRIL, also induced CLL-cell activation of NF-kappaB2. We conclude that BAFF and APRIL from NLCs can function in a paracrine manner to support leukemia cell survival via mechanisms that are distinct from those of SDF-1alpha, indicating that NLCs use multiple distinct pathways to support CLL-cell survival.
Authors:
Mitsufumi Nishio; Tomoyuki Endo; Nobuhiro Tsukada; Junko Ohata; Shinichi Kitada; John C Reed; Nathan J Zvaifler; Thomas J Kipps
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2005-04-28
Journal Detail:
Title:  Blood     Volume:  106     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-21     Completed Date:  2005-09-21     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1012-20     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, 9500 Gilman Dr, UCSD School of Medicine, La Jolla, CA 92093-0663, USA.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD14
B-Cell Activation Factor Receptor
Cell Differentiation
Cell Survival
Chemokine CXCL12
Chemokines, CXC
Coculture Techniques
Gene Expression Regulation, Neoplastic
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
Leukocytes, Mononuclear / chemistry,  physiology*
Membrane Proteins / analysis,  genetics,  physiology*
NF-kappa B / metabolism
NF-kappa B p50 Subunit
NF-kappa B p52 Subunit
Paracrine Communication*
Protein Precursors / metabolism
RNA, Messenger / analysis
Receptors, Tumor Necrosis Factor / analysis,  genetics,  physiology*
Tumor Necrosis Factor Ligand Superfamily Member 13
Tumor Necrosis Factor-alpha / analysis,  genetics,  physiology*
Grant Support
ID/Acronym/Agency:
P01-CA81534/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD14; 0/B-Cell Activation Factor Receptor; 0/CXCL12 protein, human; 0/Chemokine CXCL12; 0/Chemokines, CXC; 0/Membrane Proteins; 0/NF-kappa B; 0/NF-kappa B p50 Subunit; 0/NF-kappa B p52 Subunit; 0/Protein Precursors; 0/RNA, Messenger; 0/Receptors, Tumor Necrosis Factor; 0/TNFRSF13C protein, human; 0/TNFSF13 protein, human; 0/Tumor Necrosis Factor Ligand Superfamily Member 13; 0/Tumor Necrosis Factor-alpha
Comments/Corrections

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