| Autor: |
Lisa Pfeuffer, Viola Siegert, Julia Frede, Leonie Rieger, Riccardo Trozzo, Niklas de Andrade Krätzig, Sandra Ring, Shamim Sarhadi, Nicole Beck, Stefan Niedermeier, Mar Abril-Gil, Mohamed Elbahloul, Marianne Remke, Katja Steiger, Ruth Eichner, Julia Jellusova, Roland Rad, Florian Bassermann, Christof Winter, Jürgen Ruland, Maike Buchner |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Blood Cancer Journal, Vol 14, Iss 1, Pp 1-13 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2044-5385 |
| DOI: |
10.1038/s41408-024-01123-6 |
| Popis: |
Abstract B-cell malignancies, such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), remain incurable, with MM particularly prone to relapse. Our study introduces a novel mouse model with active RANK signaling and the TCL1 oncogene, displaying both CLL and MM phenotypes. In younger mice, TCL1 and RANK expression expands CLL-like B1-lymphocytes, while MM originates from B2-cells, becoming predominant in later stages and leading to severe disease progression and mortality. The induced MM mimics human disease, exhibiting features like clonal plasma cell expansion, paraproteinemia, anemia, and kidney and bone failure, as well as critical immunosurveillance strategies that promote a tumor-supportive microenvironment. This research elucidates the differential impacts of RANK activation in B1- and B2-cells and underscores the distinct roles of single versus combined oncogenes in B-cell malignancies. We also demonstrate that human MM cells express RANK and that inhibiting RANK signaling can reduce MM progression in a xenotransplantation model. Our study provides a rationale for further investigating the effects of RANK signaling in B-cell transformation and the shaping of a tumor-promoting microenvironment. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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