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PMID: 15860672 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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.

Blood ·Vol. 106 ·No. 3 ·2005-08-01 ·Pages 1012-20

Nishio M, Endo T, Tsukada N, Ohata J, Kitada S, Reed JC, Zvaifler NJ, Kipps TJ

Abstract

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.

MeSH Terms
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 Lipopolysaccharide Receptors 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
Chemicals
B-Cell Activation Factor Receptor CXCL12 protein, human Chemokine CXCL12 Chemokines, CXC Lipopolysaccharide Receptors Membrane Proteins NF-kappa B NF-kappa B p50 Subunit NF-kappa B p52 Subunit Protein Precursors RNA, Messenger Receptors, Tumor Necrosis Factor TNFRSF13C protein, human TNFSF13 protein, human Tumor Necrosis Factor Ligand Superfamily Member 13 Tumor Necrosis Factor-alpha
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Nishio Mitsufumi
Department of Medicine, 9500 Gilman Dr, UCSD School of Medicine, La Jolla, CA 92093-0663, USA.
Endo Tomoyuki
Tsukada Nobuhiro
Ohata Junko
Kitada Shinichi
Reed John C
Zvaifler Nathan J
Kipps Thomas J
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2004-03-0889
Published
2005-08-01
Epub
2005-00-28
Pages
1012-20
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1895149
Subset
IM
Grants
NCI NIH HHS · P01-CA81534 · United States
External Links
PubMed source DOI: 10.1182/blood-2004-03-0889 PMC Full Text View journal details
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