RelB-dependent stromal cells promote T-cell leukemogenesis.
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.
dos Santos
Nuno R
NR
Institut Curie, Centre de Recherche, Orsay, France.
Williame
Maryvonne
M
Gachet
Stéphanie
S
Cormier
Françoise
F
Janin
Anne
A
Weih
Debra
D
Weih
Falk
F
Ghysdael
Jacques
J
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*
D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA; C073701:Nfkb1 protein, mouse; D051841:Transcription Factor RelB