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Series GSE198142 Query DataSets for GSE198142
Status Public on Mar 01, 2024
Title Selective translational control by PABPC1 phase separation regulates blast crisis and target therapy resistance of chronic myeloid leukemia
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL1 fusion tyrosine kinase have revolutionized the treatment of chronic myeloid leukemia (CML). However, the development of TKI resistance and the subsequent transition from the chronic phase (CP) to blast crisis (BC) threaten CML patients. Accumulating evidence suggests that translational control is crucial for cancer development and progression. Here, we performed high throughput CRISPR/Cas9 screening and identified poly(A) binding protein cytoplasmic 1 (PABPC1) as a driver for CML-BC progression. PABPC1 preferentially improved the translation efficiency of multiple leukemogenic mRNAs with long and highly structured 5' untranslated regions, including BCR-ABL1 and its TKI-resistant mutants, through forming biomolecular condensates. Inhibiting PABPC1 significantly suppressed CML cell proliferation and attenuated disease progression, but did not affect normal hematopoiesis seriously. More importantly, we identified two novel PABPC1 inhibitors, 1,10-Phen and ML324, which inhibited BC progression and overcame TKI resistance in murine and human CML. Overall, our work identified PABPC1 as a selective translation enhancing factor in CML-BC, the genetic or pharmacological inhibition of which overcame TKI resistance and suppressed BC progression in CML.
 
Overall design PABPC1-KD RNA-seq and PABPC1 eCLIP-seq datasets.
 
Contributor(s) Sun C, Chen Z, Ma Y, Yu J
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Submission date Mar 08, 2022
Last update date Oct 30, 2024
Contact name Zhongyang Chen
E-mail(s) zhychen_96@126.com
Organization name School of Basic Medicine, Peking Union Medical College (PUMC)
Street address No.5, Dongdan Santiao, Dongcheng District
City Beijing
ZIP/Postal code 100005
Country China
 
Platforms (1)
GPL20795 HiSeq X Ten (Homo sapiens)
Samples (8)
GSM5939717 K562 WT rep1
GSM5939718 K562 WT rep2
GSM5939719 K562 PABPC1-KD rep1
Relations
BioProject PRJNA813859

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE198142_PABPC1.peaks_merge.txt.gz 909.2 Kb (ftp)(http) TXT
GSE198142_PABPC1_input_neg.bw 84.4 Mb (ftp)(http) BW
GSE198142_PABPC1_input_pos.bw 80.4 Mb (ftp)(http) BW
GSE198142_PABPC1_ip_neg.bw 71.7 Mb (ftp)(http) BW
GSE198142_PABPC1_ip_pos.bw 68.9 Mb (ftp)(http) BW
GSE198142_RAW.tar 344.3 Mb (http)(custom) TAR (of BW)
GSE198142_RNA-seq_Raw_gene_counts_matrix.txt.gz 354.4 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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