diabetic hearts. Of 838 genes, 272 were up-regulated and 566 were down-regulated, an indication that diabetes is associated with a net suppression of gene expression. A partial list of Diabetes-Induced Gene Profile Angioimmunoblastic T-cell Lymphoma is a distinct Tcell lymphoma entity originally described as a dysimmune condition. It usually manifests with generalized lymphadenopathy, 
hepatomegaly, splenomegaly, fever, sweats, and skin rash and is frequently associated with clinical and biological autoimmune manifestations. A clonal T-Cell Receptor gene rearrangement is detected in around 80% of the cases, and few recurrent cytogenetic abnormalities have been reported. Recently, we have reported mutations in isocitrate dehydrogenases 2 and Ten-Eleven Translocation 2 genes in AITL, two genes involved in epigenetic gene regulation, but to date, no driving oncogenic event has been identified. We and others have shown that Follicular Helper T cells are the normal cellular counterpart of the neoplastic component of AITL. TFH cells constitute a specialized subset of T cells which allows the selection of highaffinity B lymphocytes within germinal centers and provide helper function for antibody production. Human TFH cells express high levels of BCL6, PD1, ICOS, the chemokine CXCL13 and its receptor and secrete the cytokine IL-21. Recently, a mouse model has been proposed for AITL. It recapitulates many of the clinical and pathological features associated with AITL, including lymphadenopathy, hypergammaglobulinemia and accumulation/expansion of clonal TFH cells. This phenotype is specifically linked to heterozygous Roquin/Rc3h1 point mutation in T cells. Roquin, a RINGtype E3 ubiquitin ligase family member, has been previously identified as a regulator of autoimmune responses in mice. We thus hypothesized that in human, ROQUIN/RC3H1 alterations could occur as an initial event of the AITL oncogenic process, leading to TFH accumulation or proliferation prone to subsequent transforming events. Material and Methods The present study was approved by the institutional review board ��Comite de Protection des Personnes, Creteil, France . Written consent was 17984313 obtained from patients with lymphoma. Reactive human tonsils were collected from children ROQUIN & Human Angioimmunoblastic T Cell Lymphoma undergoing routine tonsillectomy. Oral information was given to parents. A consent form attesting the oral consent was signed by the surgeon and 11325787 given to the research team with tonsils. Twelve AITL tumor frozen tissue samples were selected on the basis of high tumor cell content. After complete immunostaining for TFH markers including PD1, ICOS and CXCL13, a semiquantitative evaluation of tumor cells was performed as previously described and cases with more than 50% tumor cells were selected for ROQUIN sequence analyses. Cell samples and AITL tissues Normal cell subsets were AZ-505 isolated from reactive human tonsils. Briefly, mononuclear cells were isolated by mechanical disruption followed by Ficoll-hypaque density gradient centrifugation. TFH cells were purified after depletion of CD19, CD8, CD14 and CD16-positive cells with magnetic beads, by cell sorting of CD4-FITC, CXCR5-PE and ICOSPC7 triple-positive cells on Mo-Flo legacy. Tonsil CD4+, CD8+ T-cells and B-cells were purified by positive selection with antibodies directed against CD4, CD8, and CD19 respectively. Neoplastic TFH cells were isolated from cryopreserved mononuclear cell suspensions of AITL lymph nod
