relb-dependent stromal cells promote t-cell leukemogenesisrelb-dependent基质细胞促进t细胞白血病生成.pdfVIP

RelB-Dependent Stromal Cells Promote T-Cell Leukemogenesis 1,2¤ 1,2 ´ 1,2 1,2 3 Nuno R. dos Santos , Maryvonne Williame , Stephanie Gachet , Franc¸oise Cormier , Anne Janin , 4 4 1,2 Debra Weih , Falk Weih , Jacques Ghysdael * ´ ´ ˆ 1 Institut Curie, Centre de Recherche, Orsay, France, 2 CNRS UMR146, Orsay, France, 3 INSERM Unite 728, Universite Paris VII, Hopital Saint-Louis, Paris, France, 4 Leibniz- Institute for Age Research – Fritz-Lipmann-Institute (FLI), Jena, Germany Abstract Background: The Rel/NF-kB transcription factors are often activated in solid or hematological malignancies. In most cases, NF-kB activation is found in malignant cells and results from activation of the canonical NF-kB pathway, leading to RelA and/or c-Rel activation. Recently, NF-kB activity in inflammatory cells infiltrating solid tumors has been shown to contribute to solid tumor initiation and progression. Noncanonical NF-kB activation, which leads to RelB activation, has also been reported in breast carcinoma, prostate cancer, and lymphoid leukemia. Methodology/Principal Findings: Here we report a novel role for RelB in stromal cells that promote T-cell leukemogenesis. RelB deficiency delayed leukemia onset in the TEL-JAK2 transgenic mouse model of human T acute lymphoblastic leukemia. Bone marrow chimeric mouse experiments showed that RelB is not required in the hematopoietic compartment. In contrast, RelB plays a role in radio-resistant stromal cells t