Critical Reviews in Oncology/Hematology 72 (2009) 91–97 Tumors that look for their springtime in APRIL E. Roosnek a , M. Burjanadze a,b , P.Y. Dietrich c , T. Matthes a , J. Passweg a , B. Huard a,b,∗ a Division of Hematology, Geneva University Hospitals, Switzerland b Departmentof Pathology-Immunology, Faculty of Medicine, Geneva, Switzerland c Division of Oncology, Geneva University Hospitals, Switzerland Accepted 28 January 2009 Contents 1. APRIL and its multiple receptors ........................................................................................ 91 2. APRIL production and tissue distribution ................................................................................ 92 3. APRIL and tumors at the benchside ..................................................................................... 93 3.1. Solid tumors .................................................................................................... 93 3.2. B-cell malignancies ............................................................................................. 93 4. APRIL and tumors at the bedside ....................................................................................... 93 4.1. Solid tumors .................................................................................................... 94 4.2. Hodgkin’s lymphoma ............................................................................................ 94 4.3. Non-Hodgkin’s lymphoma ....................................................................................... 94 4.4. Multiple myeloma ............................................................................................... 95 5. Concluding remarks ................................................................................................... 95 Reviewers ............................................................................................................ 95 Acknowledgements .................................................................................................... 96 References ............................................................................................................ 96 Biographies ........................................................................................................... 97 Abstract Inflammatory cells produce a proliferation inducing ligand (APRIL), one of the most recently cloned members of the tumor necrosis factor (TNF) family. Early experiments implicated APRIL as a promoting factor in the natural course of various cancers, reinforcing the concept that host inflammatory reactions are part of a tumor development. Recent studies have further analyzed the tumor-promoting role of APRIL in patients with solid tumors or with hematological malignancies. Here, we will review the recent literature, and provide evidence that APRIL may be a useful prognostic tool and a potential target in the treatment of some cancers. © 2009 Elsevier Ireland Ltd. All rights reserved. Keywords: Tumor; Inflammation; TNF; APRIL; DLBCL; CLL; Multiple myeloma 1. APRIL and its multiple receptors A proliferation inducing ligand (APRIL, TNFSF-13) is one of the most recently cloned members of the tumor necro- sis factor (TNF) superfamily [1,2]. APRIL is closely related ∗ Corresponding author at: Department of Patho-Immunology, Faculty of Medicine, 1 rue michel servet, Geneva, Switzerland. Tel.: +41 22 379 5811. E-mail address: bertrand.huard@unige.ch (B. Huard). to another member of the TNF family, the B-cell activa- tion factor (BAFF, TNFSF-13B). Although some BAFF and APRIL functions are similar [3], most of their functions are non-redundant, which is best illustrated by the distinct pheno- type of BAFF- and APRIL-deficient mice [4–6]. Furthermore, BAFF has a unique receptor, BAFF-R [7], whereas APRIL interacts with heparan sulfate proteoglycans (HSPG) [8,9]. Expression of BAFF and APRIL is also regulated differently, at least under pathological conditions [10]. Throughout this 1040-8428/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.critrevonc.2009.01.006