Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness

Article Article scientifique Article Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness eng 2007-01-01 author Schwaller Juerg 519654 author Schneider Pascal author Mhawech-Fauceglia Paulette 549956 author Mckee Thomas Alexander 549937 author Myit Samir 84217 author Matthes Thomas 27368 author Tschopp Jurg author Donze Olivier 23336 author Le Gal Frédérique-Anne 134548 author Huard Bertrand 133420 331-338 10.1182/blood-2006-02-001800 17190854 0006-4971 https://ashpublications.org/blood/article/109/1/331/117118/Neutrophil-derived-APRIL-concentrated-in-tumor A PRoliferation-Inducing TNF Ligand (APRIL) costimulates B-cell activation. When overexpressed in mice, APRIL induces B-cell neoplasia, reminiscent of human B-cell chronic lymphoid leukemia (B-CLL). We analyzed APRIL expression in situ in human non-Hodgkin lymphomas. APRIL up-regulation was only observed in high-grade B-cell lymphomas, diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma (BL). Up-regulation was seen in 46% and 20% of DLBCL and BL, respectively. In DLBCL, neutrophils, constitutively producing APRIL and infiltrating the tumor tissue, were the main cellular source of APRIL. Rare DLBCL cases showed a predominance of histiocytes or mesenchymal cells as APRIL source. APRIL secreted by neutrophils accumulated on tumor cells via proteoglycan binding. In addition to proteoglycans, DLBCL tumor cells expressed the APRIL signaling receptor, TACI and/or BCMA, indicating that these tumor cells are fully equipped to respond to APRIL. A retrospective clinical analysis revealed a significant correlation between high expression of APRIL in tumor lesions and decreased overall patient survival rate. Hence, APRIL produced by inflammatory cells infiltrating lymphoma lesions may increase tumor aggressiveness and affect disease outcome. B-Cell Maturation Antigen / metabolism Burkitt Lymphoma / metabolism Burkitt Lymphoma / mortality Burkitt Lymphoma / pathology Gene Expression Regulation, Neoplastic Humans Kaplan-Meier Estimate Lymphoma, B-Cell / metabolism Lymphoma, B-Cell / mortality Lymphoma, B-Cell / pathology Lymphoma, Large B-Cell, Diffuse / metabolism Lymphoma, Large B-Cell, Diffuse / mortality Lymphoma, Large B-Cell, Diffuse / pathology Lymphoma, Non-Hodgkin / metabolism Lymphoma, Non-Hodgkin / mortality Lymphoma, Non-Hodgkin / pathology Neoplasm Invasiveness Neoplasm Proteins / biosynthesis Neoplasm Proteins / genetics Neoplasm Proteins / physiology Neutrophils / metabolism Prognosis Protein Structure, Tertiary Proteoglycans / metabolism Retrospective Studies Survival Analysis Transmembrane Activator and CAML Interactor Protein / metabolism Tumor Necrosis Factor Ligand Superfamily Member 13 / biosynthesis Tumor Necrosis Factor Ligand Superfamily Member 13 / genetics Tumor Necrosis Factor Ligand Superfamily Member 13 / physiology Up-Regulation Dewey 616 Dewey 616.07 56 Département de médecine 221 137 Département de pathologie et immunologie 21F false 586 Analyses cellulaires et moléculaires des hémopathies malignes 929 476 Lymphomes MALT et réplication virale 807 Blood 109 1 91fc5726-5430-4345-a545-30403fd2dcb5 Article (Published version) Public 1-s2.0-S0006497120521617-main.pdf 556576 application/pdf a01b6f0f-8027-4393-a98c-d7ba546dd814 Erratum Public zh801707001474.pdf 58437 application/pdf Figure 7 contains an incorrect P value. The figure should read “P = .02.” openAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness	Blood			2007	227	293

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Schwaller, Juerg