Figure 5 from Schlafen 12 Modulation and Targeting in Acute Myeloid Leukemia

<p>Effects of velcrin treatment on SLFN12 expression <i>in vivo</i>. <b>A,</b> Schematic representation of the treatment regimen used for the xenograft AML mouse model using BAY 2666605 or vehicle control. <b>B,</b> Tumor growth curves of nude (NU/NU) mice treated and challenged with HEL cells. Each point represents the mean tumor volume ± SEM per group for vehicle control (5% ethanol with 95% polyethylene glycol-400)– and BAY 2666605–treated mice (<i>n</i> = 5 for control; <i>n</i> = 4 for treated). Pink bar indicates days in which mice were treated with BAY 2666605 or vehicle control. Tumor growth from the start of treatment (day 14) until the end of treatment (day 18) was analyzed using a mixed-effects linear regression model. Tumor volume was log-transformed to satisfy the normality assumption. Treatment group, time, and their interaction were included as fixed effects and mice as a random effect. The interaction was statistically significant (<i>P</i> < 0.001). The <i>P</i> value comparing treatments at day 18 is reported (*, <i>P</i> = 0.011). <b>C,</b> Tumor lysates from the experiment shown in panel (<b>B</b>) were subjected to SDS-PAGE and probed for SLFN12 protein expression. <b>D,</b> Tumor samples from the same experiment (<i>n</i> = 4 per group) were subjected to RNA-seq. Volcano plot shows the differentially up- or downregulated genes between the velcrin treatment group and the vehicle control group. Genes deemed statistically significant are highlighted in red. Data are from four biological replicates per group (see also Supplementary Fig. S2). <b>E</b> and <b>F,</b> Gene ontology (GO) analysis of differentially expressed genes that were (<b>E</b>) downregulated or (<b>F</b>) upregulated in mouse tumors treated with BAY 2666605 compared with vehicle control–treated mice. Relevant pathways associated with differentially expressed genes are underlined in red. BAY, BAY 2666605; SQ, subcutaneous. [<b>A,</b> Created in BioRender. Guillen Magana, J. (2025) <a href="https://BioRender.com/aqz79jx" target="_blank">https://BioRender.com/aqz79jx</a>.]</p>