RelB-dependent stromal cells promote T-cell leukemogenesis.

Area of Science:

• Molecular Biology
• Cancer Biology
• Immunology

Background:

• Rel/NF-kappaB transcription factors are frequently activated in malignancies.
• Canonical NF-kappaB pathway activation (RelA, c-Rel) is common in cancer cells.
• Noncanonical NF-kappaB pathway activation (RelB) is implicated in certain cancers and inflammatory cell roles.

Purpose of the Study:

• To investigate the role of RelB in stromal cells during T-cell leukemogenesis.
• To determine if RelB in non-hematopoietic cells influences leukemia development.

Main Methods:

• Utilized the TEL-JAK2 transgenic mouse model for T acute lymphoblastic leukemia.
• Employed bone marrow chimeric mouse experiments to distinguish hematopoietic and stromal cell roles.
• Assessed the impact of RelB deficiency on leukemia onset and severity.

Main Results:

• RelB deficiency significantly delayed leukemia onset in the studied mouse model.
• RelB was found to be dispensable in the hematopoietic compartment.
• RelB in radio-resistant stromal cells was crucial for accelerating leukemia onset and increasing disease severity.

Conclusions:

• This study reveals a novel pro-leukemogenic role for RelB in stromal cells.
• Identified a critical crosstalk between non-hematopoietic stromal cells and leukemic cells mediated by RelB.
• Suggests the noncanonical NF-kappaB pathway, via RelB in the tumor microenvironment, has a pro-oncogenic function.