References of "Wunderlich, F. T"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailAberrant 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

in Leukemia (2017), 32(1), 72-82

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 ... [more ▼]

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. [less ▲]

Detailed reference viewed: 38 (3 UL)