title: RelB-dependent stromal cells promote T-cell leukemogenesis.
abstract: BACKGROUND
  The Rel/NF-kappaB transcription factors are often activated in solid or hematological malignancies. In most cases, NF-kappaB activation is found in malignant cells and results from activation of the canonical NF-kappaB pathway, leading to RelA and/or c-Rel activation. Recently, NF-kappaB activity in inflammatory cells infiltrating solid tumors has been shown to contribute to solid tumor initiation and progression. Noncanonical NF-kappaB activation, which leads to RelB activation, has also been reported in breast carcinoma, prostate cancer, and lymphoid leukemia.
  
  
  RESULTS
  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
  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-kappaB pathway may also play a pro-oncogenic role in cancer microenvironmental cells.
authors.affiliation: Institut Curie, Centre de Recherche, Orsay, France.
authors.forename: Nuno R
authors.initials: NR
authors.lastname: dos Santos
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Williame
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Gachet
authors.forename: Françoise
authors.initials: F
authors.lastname: Cormier
authors.forename: Anne
authors.initials: A
authors.lastname: Janin
authors.forename: Debra
authors.initials: D
authors.lastname: Weih
authors.forename: Falk
authors.initials: F
authors.lastname: Weih
authors.forename: Jacques
authors.initials: J
authors.lastname: Ghysdael
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D052002:NF-kappa B p50 Subunit / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D051841:Transcription Factor RelB / Q000235:genetics / Q000378:metabolism*
chemical_list: D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA; C073701:Nfkb1 protein, mouse; D051841:Transcription Factor RelB