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.
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.
Nishio
Mitsufumi
M
Department of Medicine, 9500 Gilman Dr, UCSD School of Medicine, La Jolla, CA 92093-0663, USA.
Endo
Tomoyuki
T
Tsukada
Nobuhiro
N
Ohata
Junko
J
Kitada
Shinichi
S
Reed
John C
JC
Zvaifler
Nathan J
NJ
Kipps
Thomas J
TJ
D053265:B-Cell Activation Factor Receptor; D002454:Cell Differentiation; D002470:Cell Survival; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D018920:Coculture Techniques; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000502:physiology*; D018950:Lipopolysaccharide Receptors; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D019899:Paracrine Communication; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D053265:B-Cell Activation Factor Receptor; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D018950:Lipopolysaccharide Receptors; D008565:Membrane Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D011498:Protein Precursors; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; C435926:TNFRSF13C protein, human; C114631:TNFSF13 protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha