Fig. 7. Inhibition of the spliceosome is a promising therapeutic strategy in myeloma.

a Bioluminescence imaging of luciferase-labeled MM.1S cells implanted in mice treated with either vehicle (left panel, n = 6) or 3 mg kg⁻¹ E7107 (right panel, n = 6). b Mean +/− S.D. luciferase intensity shows lower tumor burden in E7107-treated mice. Green arrows indicate drug administration days (14–18, 21–25). c E7107 leads to significant improvement in murine survival (p = 0.01 by two-sided log-ranked test). d Treatment of primary bone marrow aspirate samples from PI-refractory myeloma patients at various doses of E7107 for 24 h shows significant cytotoxicity to CD138 + MM plasma cells at low-nM concentrations but minimal effects on other (CD138−) hematopoietic cells (n = 2 technical replicates; mean is represented by bars). e Heatmap of CRISPR-Cas9 essentiality screen data analysis in the Cancer Dependency Map (www.depmap.org; Avana 18Q4 release) of core spliceosomal subunits among all tested tumor cell types. f Analysis of MMRF CoMMpass data (research.themmrf.org; release IA11) summarizing mutations with possible functional effects in numerous splicing-related factors, as defined by Seiler et al.⁵², within MM patient plasma cells.