Chronic lymphocytic leukemia disease progression is accelerated by APRIL / TACI interaction in the TCL1 transgenic mouse model

Lascano, V.; Guadagnoli, M.; Schot, J. G.; Luijks, D. M.; Guikema, J. E.; Cameron, K.; Hahne, M.; Pals, S.; Slinger, E.; Kipps, T. J.; van Oers, M. H.; Eldering, E.; Medema, J. P.; Kater, A. P.




Although in vitro studies pointed to the TNF family member APRIL in mediating survival of chronic lymphocytic leukemia (CLL), clear evidence for a role of APRIL in leukemogenesis and progression in CLL is lacking. We observed that APRIL significantly prolonged in vitro survival of CD5+B220dull leukemic cells derived from the murine Emu-TCL1-Tg (TCL1-Tg) model for CLL. APRIL-TCL1 double-Tg mice showed a significant earlier onset of leukemia, disruption of splenic architecture and survival of double-Tg mice was significantly reduced. Interestingly, clonal evolution of CD5+B220dull cells, as judged by BCR clonality, seemed not to be accelerated by APRIL and both mouse strains were oligoclonal at 4 months. Furthermore, although APRIL binds different receptors, APRIL-mediated leukemic cell survival depended on TACI ligation. These findings indicate an important role for APRIL in CLL and indicate that the APRIL-TACI interaction might be a selective novel therapeutic target for human CLL.

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blood-2013-04-497693 [pii] 10.1182/blood-2013-04-497693

1528-0020 (Electronic) 0006-4971 (Linking)

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