Extended Data Fig. 7. The effect of imetelstat’s triple G-containing mismatch control on AML.
a, Oligonucleotide sequences of imetelstat, mismatch 1 (MM1), and mismatch 2 (GGG; MM2). Celltiter analysis of 14 human hematopoietic cell lines treated with different concentrations (0.25 microM, 1 microM, 4 microM) of MM1, MM2, or imetelstat over a 4-week period. Data pooled from three technical replicates per condition from n = 2 independent experiments. Log2 fold changes of cell growth (celltiter-assay) of drug-treated conditions compared to vehicle controls are presented as heatmap. b, Median fluorescent intensities of anti-DNA G-quadruplex antibody (1H6) in editing-control (n = 5 biological replicates, that is native, Cas9, empty vector, CD33-sg1, CD33-sg2) NB4 cell lines treated with PBS, MM1, MM2, or imetelstat, and gated on G1 (left), or S/G2/M cell cycle phases (right). Each dot represents the mean of three technical replicates from one representative out of three independent experiments. c, CellROX measurement of n = 5 editing controls or n = 2 FADS2-edited (FADS2-sg1, FADS2-sg2) NB4 treated with PBS, MM1, MM2, or imetelstat. Each dot represents the mean of three technical replicates per cell line from one representative out of four independent experiments. b,c, One-way-ANOVA analysis adjusted for multiple comparisons: P < 1 × 10−4 (PBS versus MM2 in G1 and S/G2/M; b), P < 1 × 10−4 (PBS versus imetelstat in G1 and S/G2/M; b), P < 1 × 10−4 (editing controls+ PBS versus MM1; c), P < 1 × 10−4 (editing controls + PBS versus MM2; c), P < 1 × 10−4 (editing controls + PBS versus imetelstat; c), P = 2 × 10−4 (MM2-treated editing controls versus FADS2-edited cells; c), P < 1 × 10−4 (imetelstat-treated editing controls versus FADS2-edited cells; c). d, Celltiter analysis on NB4 treated with PBS, MM1, MM2 or imetelstat, and in combination with ferrostatin-1 (left) or DFOM (right). N = 3 technical replicates per condition from one representative out of two independent experiments in total. One-way-ANOVA adjusted for multiple comparisons: P < 1 × 10−4 (PBS versus MM2), P < 1 × 10−4 (PBS versus imetelstat). e, Peripheral blood AML burden in AML PDX (RCH-11) treated with PBS (n = 6), MM1, (n = 5), MM2 (n = 5), or imetelstat (n = 6). One-way-ANOVA adjusted for multiple comparisons on day 17: P = 1.83 × 10−2 (PBS versus MM2), P = 1.2 × 10−3 (PBS versus imetelstat).