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Series GSE141572 Query DataSets for GSE141572
Status Public on Nov 27, 2020
Title Ikaros and CK2 regulate expression of Bcl-xL and chemosensitivity in high-risk B-cell acute lymphoblastic leukemia
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary High-risk B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive disease, often characterized by resistance to chemotherapy. A frequent feature of high-risk B-ALL is loss of function of the Ikaros tumor suppressor. In leukemia, Ikaros’ function is impaired by oncogenic Casein Kinase II (CK2), which is overexpressed in B-ALL. Phosphorylation by CK2 reduces Ikaros binding to the promoter of its target gene, particularly Bcl-xL. This results in a loss of Ikaros-mediated repression of Bcl-xL and in increased expression of Bcl-xL. Increased expression of Bcl-xL and/or CK2, as well as reduced Ikaros expression, are associated with resistance to doxorubicin treatment. Molecular and pharmacological inhibition of CK2 with a specific inhibitor CX-4945, enhances Ikaros-mediated repression of Bcl-xL and increases sensitivity to doxorubicin. Combination treatment with CX-4945 and doxorubicin show synergistic therapeutic effects in vitro and in preclinical models of high-risk B-ALL. Results reveal a novel signaling network that regulates chemoresistance in leukemia and lays the groundwork for clinical testing of CK2 inhibitors in combination with doxorubicin for the treatment of hematopoietic malignancies.
Overall design Examine the genome-wide binding of Ikaros in JM-1, REH and 697 B-ALL leukemia cells and also the effect of CK2 inhibitor-CX-4945 on the Ikaros binding profiling in JM-1 cells.
Contributor(s) Song C, Ge Z, Ding Y, Kawasawa YI, Dovat S
Citation(s) 32396934, 33531656
Submission date Dec 06, 2019
Last update date Jun 03, 2021
Contact name chunhua song
Phone 717-531-1841
Organization name Pennsyvania State University College of Medicine
Department Pediatrics
Street address 500 University Drive
City Hershey
State/province PA
ZIP/Postal code 17033
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (11)
GSM4207253 JM1-WT-IK-1
GSM4207254 JM1-CX-d1-IK-1
GSM4207255 REH-WT-IK-2
BioProject PRJNA593992
SRA SRP234975

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Supplementary file Size Download File type/resource
GSE141572_Nalm6-CX4945_annotation.txt.gz 1.6 Mb (ftp)(http) TXT
GSE141572_peaks_annotation_JM1-CX-anti-IK.txt.gz 2.0 Mb (ftp)(http) TXT
GSE141572_peaks_annotation_JM1-WT-anti-IK.txt.gz 924.7 Kb (ftp)(http) TXT
GSE141572_peaks_annotation_REH-WT-anti-IK.txt.gz 1.9 Mb (ftp)(http) TXT
GSE141572_peaks_annotationin_697-WT-anti-IK.txt.gz 517.8 Kb (ftp)(http) TXT
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Processed data are available on Series record

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