APRIL promotes B-1 cell-associated neoplasm.
A tumor-supporting role for the TNF-like ligand APRIL has been suggested. Here we describe that 9- to 12-month-old APRIL transgenic mice develop lymphoid tumors that originate from expansion of the peritoneal B-1 B cell population. Aging APRIL transgenic mice develop progressive hyperplasia in mesenteric lymph nodes and Peyer's patches, disorganization of affected lymphoid tissues, mucosal and capsular infiltration, and eventual tumor cell infiltration into nonlymphoid tissues such as kidney and liver. We detected significantly increased APRIL levels in sera of B cell chronic lymphoid leukemia (B-CLL) patients, indicating that APRIL promotes onset of B-1-associated neoplasms and that APRIL antagonism may provide a therapeutic strategy to treat B-CLL patients.
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, UAM Campus Cantoblanco, E-28049 Madrid, Spain.
Lourdes
L
Planelles
Carla E
CE
Carvalho-Pinto
Gijs
G
Hardenberg
Salette
S
Smaniotto
Wilson
W
Savino
Ruth
R
Gómez-Caro
Melchor
M
Alvarez-Mon
Joan
J
de Jong
Eric
E
Eldering
Carlos
C
Martínez-A
Jan Paul
JP
Medema
Michael
M
Hahne
D000375:Aging; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D015448:Leukemia, B-Cell / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008221:Lymphoid Tissue / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000097:blood; D013154:Spleen / Q000254:growth & development / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
C490341:ANP32B protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; C491959:Tnfsf13 protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha