%0 Journal Article
%T RelB-Dependent Stromal Cells Promote T-Cell Leukemogenesis
%A Nuno R. dos Santos
%A Maryvonne Williame
%A St谷phanie Gachet
%A Franˋoise Cormier
%A Anne Janin
%A Debra Weih
%A Falk Weih
%A Jacques Ghysdael
%J PLOS ONE
%D 2008
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0002555
%X Background The Rel/NF-百B transcription factors are often activated in solid or hematological malignancies. In most cases, NF-百B activation is found in malignant cells and results from activation of the canonical NF-百B pathway, leading to RelA and/or c-Rel activation. Recently, NF-百B activity in inflammatory cells infiltrating solid tumors has been shown to contribute to solid tumor initiation and progression. Noncanonical NF-百B 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 to accelerate leukemia onset and increase disease severity. Conclusions/Significance The present results are the first to uncover a role for RelB in the crosstalk between non-hematopoietic stromal cells and leukemic cells. Thus, besides its previously reported role intrinsic to specific cancer cells, the noncanonical NF-百B pathway may also play a pro-oncogenic role in cancer microenvironmental cells.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0002555