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. 2023 Oct 30;5(1):47–65. doi: 10.1038/s43018-023-00653-5

Fig. 5. Lipid ROS scavenging diminishes imetelstat efficacy.

Fig. 5

a,b, CellROX Green (a) and C11-BODIPY (b) flow cytometry on NB4, MV411, KO52 and TF1 treated with imetelstat (4 μM) or vehicle control (PBS). n = 6 replicates pooled from two experiments. Time points of analysis were 24 h (NB4) and day 4 (MV411), day 8 (KO52) and day 5 (TF1). Data are presented as mean ± s.e.m. a, One-way ANOVA was used and adjusted for multiple comparisons. NB4, P < 1 × 10−4 (NB4 PBS versus imetelstat), P = 9 × 10−4 (imetelstat versus imetelstat + ferrostatin); MV411, P = 1 × 10−4 (PBS versus imetelstat), P = 1 × 10−4 (imetelstat versus imetelstat + ferrostatin); KO52, P = 1.84 × 10−2 (PBS versus imetelstat), P = 1.95 × 10−2 (imetelstat versus imetelstat + ferrostatin); TF1, P = 6.2 × 10−3 (PBS versus imetelstat), P < 1 × 10−4 (imetelstat versus imetelstat + ferrostatin). b, An unpaired two-sided t-test was used. NB4, P < 1 × 10−4; MV411, P = 1 × 10−4; KO52, P = 9.4 × 10−3; TF1, P < 1 × 10−4. c, C11-BODIPY and ACSL4 messenger RNA (mRNA) analysis on sorted viable CD45+ splenic cells from imetelstat- compared to PBS-treated PDXs from the preclinical trial presented in Fig. 2. C11-BODIPY data (n = 9 PDXs from three individual AML samples with three PDXs per patient sample) are presented as mean ± s.e.m. ACSL4 mRNA data (n = 6 PDXs from the same three individual AML samples with two PDXs per patient sample) are presented as violin plots. Statistics are based on an unpaired two-sided t-test: P < 1 × 10−4 (MFI C11-BODIPY, top), P = 2.145 × 10−1 (MFI C11-BODIPY, bottom); P = 1 × 10−4 (ACSL4, top), P = 9.53 × 10−1 (ACSL4, bottom). d–f, AML PDX treated with vehicle, liproxstatin-1, imetelstat or a combination of liproxstatin-1 with imetelstat for 2 weeks. n = 12 PDX per treatment group. C11-BODIPY (d) and CellROX (e) flow cytometry on splenic CD45+ singlets. PB chimerism (f) at the end of treatment. Data are presented as mean ± s.e.m. (d–f). One-way ANOVA was used and adjusted for multiple comparisons. P = 2.7 × 10−3 (vehicle versus imetelstat), P = 1 × 10−3 (imetelstat versus imetelstat + liproxstatin-1) (d). P = 6.4 × 10−3 (vehicle versus imetelstat), P = 1.934 × 10−1 (imetelstat versus imetelstat + liproxstatin-1) (e). P = 3.3 × 10−3 (vehicle versus imetelstat), P = 4.21 × 10−2 (imetelstat versus imetelstat + liproxstatin-1) (f).

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