PLoS ONE (Jan 2008)

RelB-dependent stromal cells promote T-cell leukemogenesis.

  • Nuno R dos Santos,
  • Maryvonne Williame,
  • Stéphanie Gachet,
  • Françoise Cormier,
  • Anne Janin,
  • Debra Weih,
  • Falk Weih,
  • Jacques Ghysdael

DOI
https://doi.org/10.1371/journal.pone.0002555
Journal volume & issue
Vol. 3, no. 7
p. e2555

Abstract

Read online

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.