| Autor: |
Hahn, M., Burckert, J.-P., Luttenberger, C. A., Klebow, S., Hess, M., Al-Maarri, M., Vogt, M., Reissig, S., Hallek, M., Wienecke-Baldacchino, Anke, Buch, T., Muller, Claire, Pallasch, C. P., Wunderlich, F. T., Waisman, A., Hovelmeyer, N. |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Leukemia, 32(1), 72-82. England (2017). |
| Popis: |
The pathogenesis of chronic lymphocytic leukemia (CLL) has been linked to constitutive NF-kappaB activation but the underlying mechanisms are poorly understood. Here we show that alternative splicing of the negative regulator of NF-kappaB and tumor suppressor gene CYLD regulates the pool of CD5(+) B cells through sustained canonical NF-kappaB signaling. Reinforced canonical NF-kappaB activity leads to the development of B1 cell-associated tumor formation in aging mice by promoting survival and proliferation of CD5(+) B cells, highly reminiscent of human B-CLL. We show that a substantial number of CLL patient samples express sCYLD, strongly implicating a role for it in human B-CLL. We propose that our new CLL-like mouse model represents an appropriate tool for studying ubiquitination-driven canonical NF-kappaB activation in CLL. Thus, inhibition of alternative splicing of this negative regulator is essential for preventing NF-kappaB-driven clonal CD5(+) B-cell expansion and ultimately CLL-like disease. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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