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. Author manuscript; available in PMC: 2022 Nov 15.
Published in final edited form as: Nat Cancer. 2022 May 9;3(5):595–613. doi: 10.1038/s43018-022-00366-1

Figure 2. IMiDs effectively target IKAROS protein for degradation and show therapeutic efficacy in MLL-r AML.

Figure 2.

a, Western blot analysis for IKAROS protein following treatment of the MOLM13 cell line for 5 h with increasing doses of THAL, LEN, POM and CC220, using GAPDH as a loading control. b, Proliferation assay measuring cell number over time for the MV4;11 and MOLM13 cell lines treated with vehicle-control (DMSO), THAL, LEN, POM and CC220. Data represent mean+/−SD (n=3). c, Dose response curves for MV4;11 and MOLM13 cell lines using THAL, LEN, POM and CC220. Data represent mean+/−SD (n=6) with non-linear regression curve fit shown. Percentage indicated as a proportion. d, Calculated absolute IC50 and 95% confidence intervals for MOLM13, OCI-AML2 and MV4;11 AML cell lines, assessed by proliferation assay at Day 18. e, Scatterplot for MS determination of IMiD substrates 5 h after indicated drug treatment in the MOLM13 cell line. Data represent the Log-fold change in abundance and log10(p-value). p-value determined by moderated t-test as implemented by the Bioconductor Limma package. f, Schematic depicting generation of MOLM13 cell lines with IKAROS overexpression constructs treated with DMSO, LEN (5 uM), and CC220 (1 uM) for 5 hours. g, Western Blot showing IKAROS overexpression constructs, h, Proliferation assay showing rescue of antiproliferative effects with overexpressed, non-degradable IKAROS (Q146H). Data represent mean +/− SEM. p-value determined by paired, two-tail t-test.