| First Author | dos Santos NR | Year | 2008 |
| Journal | PLoS One | Volume | 3 |
| Issue | 7 | Pages | e2555 |
| PubMed ID | 18596915 | Mgi Jnum | J:137965 |
| Mgi Id | MGI:3803501 | Doi | 10.1371/journal.pone.0002555 |
| Citation | dos Santos NR, et al. (2008) RelB-dependent stromal cells promote T-cell leukemogenesis. PLoS One 3(7):e2555 |
| abstractText | 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. 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-kappaB pathway may also play a pro-oncogenic role in cancer microenvironmental cells. |
