Published in
Springer Nature [academic journals on nature.com], Leukemia, 2(30), p. 351-360, 2015
DOI: 10.1038/leu.2015.286
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The SF3B1 inhibitor spliceostatin A (SSA) elicits apoptosis in chronic lymphocytic leukaemia cells through downregulation of Mcl-1
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Stuart James Blakemore ,
R. C. Dobson,
M. D. Blunt,
M. J. J. Rose-Zerilli,
R. Walewska,
A. Duncombe,
D. Oscier,
K. Koide,
F. Forconi,
G. Packham,
M. Yoshida,
M. S. Cragg,
J. C. Strefford,
A. J. Steele
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Abstract
The pro-survival Bcl-2 family member Mcl-1 is expressed in chronic lymphocytic leukaemia (CLL), with high expression correlated with progressive disease. The spliceosome inhibitor spliceostatin A (SSA) is known to regulate Mcl-1 and so here we assessed the ability of SSA to elicit apoptosis in CLL. SSA induced apoptosis of CLL cells at low nanomolar concentrations in a dose- and time-dependent manner, but independently of SF3B1 mutational status, IGHV status and CD38 or ZAP70 expression. However, normal B and T cells were less sensitive than CLL cells (P=0.006 and P