Article (Scientific journals)
Aberrant splicing of the tumor suppressor CYLD promotes the development of chronic lymphocytic leukemia via sustained NF-kappaB signaling.
Hahn, M.; Burckert, J.-P.; Luttenberger, C. A. et al.
2017In Leukemia, 32 (1), p. 72-82
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Abstract :
[en] 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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Hahn, M.
Burckert, J.-P.
Luttenberger, C. A.
Klebow, S.
Hess, M.
Al-Maarri, M.
Vogt, M.
Reissig, S.
Hallek, M.
Wienecke-Baldacchino, Anke ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Buch, T.
Muller, Claire ;  University of Luxembourg > Faculty of Language and Literature, Humanities, Arts and Education (FLSHASE) > Luxembourg Centre for Educational Testing (LUCET)
Pallasch, C. P.
Wunderlich, F. T.
Waisman, A.
Hovelmeyer, N.
More authors (6 more) Less
External co-authors :
yes
Language :
English
Title :
Aberrant splicing of the tumor suppressor CYLD promotes the development of chronic lymphocytic leukemia via sustained NF-kappaB signaling.
Publication date :
01 June 2017
Journal title :
Leukemia
ISSN :
1476-5551
Publisher :
Nature Publishing Group, United Kingdom
Volume :
32
Issue :
1
Pages :
72-82
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 28 April 2018

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