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Image Search Results
Journal: Blood
Article Title: Targeting WDR5/ATAD2 signaling by the CK2/IKAROS axis demonstrates therapeutic efficacy in T-ALL
doi: 10.1182/blood.2024024130
Figure Lengend Snippet: The combination of CX-4945 and WDR5 disruption has a synergistic antileukemic effect in the T-ALL mice model. (A) Schematic representation of the human T-ALL CEM cell-xenograft mouse model (CEM xenograft). CEM (2 × 10 5 per mouse) were IV injected into NCG mice, and the following 4 groups of mice were established: group 1 (vehicle control); group 2 (CX-4945 daily through gavage at 100 mg/kg for 25 days); group 3 (WDR5 inhibitor OICR-9429 every 2 days through intraperitoneal injection at 60 mg/kg for 25 days); and group 4 (CX-4945 and OICR-9429 combination treatment using the same doses as provided previously). (B) Comparison of Kaplan-Meier survival curves in the combination of CX-4945 and WDR5 inhibitor OICR-9429 compared with either single drug control of CEM-xenograft mouse models. The mice were treated with the indicated drugs for 25 days. (C-D) Spleen images (C) and weights (D) of 4 groups of mice posttreatment. (E) The percentage of human CD45 + and CD7 + cells in the spleen and BM from 4 groups of mice post-treatment. (F-G) Representative immunohistological images (F) and quantitation data (G) of human CD45 in the spleen from 4 groups of mice post-treatment. (H) The protein level of WDR5 and ATAD2 and the internal control of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the spleen tissues of the mice after the treatment. (I) mRNA level of WDR5 , ATAD2 , CCNE2 , and CDK2 in the spleen tissues of the mice after the treatment. Scale bar, 50 μm. ∗∗∗ P < .001. i.g., intragastic gavage; i.p., intraperitoneal injection; OI, OICR-9429.
Article Snippet: Oncogenic roles of ATAD2 by regulating cell cycle progression in T-ALL. (A) The efficiency of
Techniques: Disruption, Injection, Control, Comparison, Quantitation Assay
supplemental Table 3 ), PDX-P2 (Pt. T-ALL-P2), and PDX-P3 (Pt. T-ALL-P3). (B) Comparison of percentage of human CD45 + CD7 + cells in the spleen of the mice in combo group vs either single drug controls. (C-E) Comparison of mRNA level of WDR5 , ATAD2 , CCNE2 , and CDK2 in combo group vs either single drug controls in the spleen of the mouse models. The mice in panels A-E were treated with the indicated drugs for 25 days, and then, when the vehicle mice met the early removal criteria due to the excessive leukemia burden, the mice were euthanized and the single cells were isolated from the spleen for flow cytometry analysis; the mRNA of the cells was prepared for qPCR analysis. ∗∗∗ P < .001. OI, OICR-9429. " width="100%" height="100%">
Journal: Blood
Article Title: Targeting WDR5/ATAD2 signaling by the CK2/IKAROS axis demonstrates therapeutic efficacy in T-ALL
doi: 10.1182/blood.2024024130
Figure Lengend Snippet: Therapeutic efficacy of the combination of CX-4945 and WDR5 inhibitor in patient-derived T-ALL leukemia-xenograft (PDX) mouse model. (A) Comparison of Kaplan-Meier survival curves in the combination of CX-4945 and WDR5 inhibitor OICR-9429 compared with either single drug controls in 3 different PDX mouse models: PDX-P1 (Patient, [Pt.] T-ALL-P1 in
Article Snippet: Oncogenic roles of ATAD2 by regulating cell cycle progression in T-ALL. (A) The efficiency of
Techniques: Drug discovery, Derivative Assay, Comparison, Isolation, Flow Cytometry
Journal: Blood
Article Title: Targeting WDR5/ATAD2 signaling by the CK2/IKAROS axis demonstrates therapeutic efficacy in T-ALL
doi: 10.1182/blood.2024024130
Figure Lengend Snippet: Identifying ATAD2 as the downstream target on CX-4945–mediated transcriptional repression of WDR5 in T-ALL. (A-B) Effect of WDR5 KD on ATAD2 expression in mRNA level (A) and protein level (B) of CEM (left) and MOLT4 (right) cells. (C) Overlapping DEGs from the RNA-seq data in CEM cells treated with CX-4945 or WDR5 inhibitor. (D) Heat map of the top overlapped DEGs in the 2 RNA-seq analyses. (E-F) Effect of combination of CX-4945 (CX) and WDR5 inhibitor OICR-9429 (OI) on the expression of ATAD2 compared with a single drug in mRNA level (E) and protein level (F) in CEM cells. (G) Effect of WDR5 on the activity of the ATAD2 promoter assessed by luciferase reporter assay in 293T cells. (H) Effect of WDR5 KD on the H3K4me3 enrichment in the promoter region of ATAD2 in CEM cells by qChIP assay. (I-J) Effect of CX-4945 on WDR5 binding and H3K4me3 enrichment at the ATAD2 promoter in CEM cells by qChIP assay. Panels H-J are representative of 3 qChIP assays. ∗ P < .05; ∗∗ P < .01; ∗∗∗ P < .001. IgG, immunoglobulin G; OI, OICR-9429.
Article Snippet: Oncogenic roles of ATAD2 by regulating cell cycle progression in T-ALL. (A) The efficiency of
Techniques: Expressing, RNA Sequencing, Activity Assay, Luciferase, Reporter Assay, Binding Assay
Journal: Blood
Article Title: Targeting WDR5/ATAD2 signaling by the CK2/IKAROS axis demonstrates therapeutic efficacy in T-ALL
doi: 10.1182/blood.2024024130
Figure Lengend Snippet: Oncogenic roles of ATAD2 by regulating cell cycle progression in T-ALL. (A) The efficiency of ATAD2 KD by shRNA (sh ATAD2 ) vs scramble shRNA control (shNC) in CEM (left) and MOLT4 (right) cells by western blot. (B) Effect of ATAD2 KD vs shNC on cell proliferation in CEM (left) and MOLT4 (right) cells. (C-D) Effect of ATAD2 KD vs shNC on cell cycle progression in CEM cells (C, representative images; D, bar graph). (E-F) Effect of ATAD2 silence by shRNA vs shNC on Kaplan-Meier survival curves (E), and percentage of human CD45 + CD7 + cells (F) in the spleen and BM of the xenograft mouse model. The mice were IV injected with the CEM-shNC or CEM-sh ATAD2 cells, respectively, for 28 days, and the single cells were prepared and analyzed. (G) Comparison of ATAD2 mRNA level in our T-ALL cohorts vs normal BM controls. The mRNA levels were determined by qPCR assay. (H) Association of ATAD2 expression with relapse in our cohort. (I) Comparison of ATAD2 mRNA levels in 5 pairs of T-ALL newly diagnosed samples vs relapsed ones. ∗ P < .05; ∗∗ P < .01; ∗∗∗ P < .001.
Article Snippet: Oncogenic roles of ATAD2 by regulating cell cycle progression in T-ALL. (A) The efficiency of
Techniques: shRNA, Control, Western Blot, Injection, Comparison, Expressing