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Figure 1 from Schlafen 12 Modulation and Targeting in Acute Myeloid Leukemia

Year: 2025
Type: other
Abstract: SLFN12 expression and velcrin sensitivity of leukemic lines. A, Box plots of SLFN12 mRNA expression in various cancer types analyzed from the TCGA Pan-Cancer dataset using the University of California Santa Cruz Xena Browser portal. B, Immunoblotting analysis of PDE3B, PDE3A, and SLFN12 in established leukemia cell lines (HEL, K-562, KG-1, SET-2, U937, OCI-AML-5, and MV-4-11). C, Dose–response curves for cell viability of the indicated leukemia cell lines upon treatment with increasing concentrations of BAY 2666605 for 4 days, assessed by WST-1 assays. For each cell line, data represent means ± SEM of three independent experiments, each done in triplicate. D, IC50 values for the indicated lines were calculated by fitting a nonlinear regression analysis using the “log (inhibitor) vs. response - three parameters” function in GraphPad Prism software (v.10). E,SLFN12 mRNA expression of HEL cells was assessed by qRT-PCR normalized to GAPDH, using a non-targeting siRNA as a control. Data are expressed as the percentage of SLFN12 mRNA expression over control (%) and represent means ± SEM of three independent experiments, each conducted in triplicate. Statistical analysis was performed using a one-sample Student t test; **, P ≤ 0.01. F, Dose–response curve of HEL cells 4 days following transfection with control or SLFN12-targeting siRNA and treatment with increasing concentrations of BAY 2666605, as measured by WST-1. Data represent cell viability normalized to siRNA control and displayed as means ± SEM of three independent experiments, each conducted in triplicate. IC50 values for the indicated lines were calculated by fitting a nonlinear regression analysis using the “log (inhibitor) vs. response - three parameters” function in GraphPad Prism software (v.10). G, Clonogenic assay of HEL cells transfected with control or SLFN12-targeting siRNA and treated with the indicated concentrations of BAY 2666605 for 7 days. Leukemic colony formation (CFU-L) was calculated as percent colony formation relative to vehicle control (DMSO-treated cells) and means ± SEM of three independent experiments are presented. Each dot represents an independent experiment. Statistical significance was determined using an ordinary two-way ANOVA, followed by a Tukey multiple comparisons test; ns, not significant, *, P ≤ 0.05; ***, P ≤ 0.001; ****, P ≤ 0.0001. ACC, adrenocortical carcinoma; BAY, BAY 2666605, BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DLBC, lymphoid neoplasm diffuse large B-cell lymphoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LAML, acute myeloid leukemia; LGG, brain lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MESO, mesothelioma; OV, ovarian serous cystadenocarcinoma; PAAD, PANCREATIC adenocarcinoma; PCPG, pheocromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, stomach adenocarcinoma; TGCT, testicular germ cell tumors; THCA, thyroid carcinoma; THYM, thymoma; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma; UVM, uveal melanoma.
Subfield: Hematology
Field: Medicine
Open Access status: gold
OpenAlex ID: W4416300036
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