Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

Wnt/Ca2+/NFAT signaling maintains survival of Ph+ leukemia cells upon inhibition of Bcr-Abl

ABSTRACT: Although Bcr-Abl kinase inhibitors have proven effective in the treatment of chronic myeloid leukemia (CML), they generally fail to completely eradicate Bcr-Abl+ leukemia cells. To identify genes whose inhibition sensitizes Bcr-Abl+ leukemias to killing by Bcr-Abl inhibitors, we performed an RNAi-based synthetic lethal screen with imatinib in CML cells. This screen identified numerous components of a Wnt/Ca2+/NFAT signaling pathway. Antagonism of this pathway led to impaired NFAT activity, decreased cytokine production and enhanced sensitivity to Bcr-Abl inhibition. Furthermore, NFAT inhibition with cyclosporin A facilitated leukemia cell elimination by the Bcr-Abl inhibitor dasatinib and markedly improved survival in a mouse model of Bcr-Abl+ acute lymphoblastic leukemia (ALL). Targeting this pathway in combination with Bcr-Abl inhibition could improve treatment of Bcr-Abl+ leukemias. We utilized a genome-wide shRNA library in combination with microarray analysis to screen for gene targets in chronic myeloid leukemia cells that cooperate with imatinib.

ORGANISM(S): Homo sapiens

SUBMITTER: Tzu Lip Phang 

PROVIDER: E-GEOD-21499 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

Json Xml
altmetric image

Publications

Although Bcr-Abl kinase inhibitors have proven effective in the treatment of chronic myeloid leukemia (CML), they generally fail to eradicate Bcr-Abl(+) leukemia cells. To identify genes whose inhibition sensitizes Bcr-Abl(+) leukemias to killing by Bcr-Abl inhibitors, we performed an RNAi-based synthetic lethal screen with imatinib mesylate in CML cells. This screen identified numerous components of a Wnt/Ca(2+)/NFAT signaling pathway. Antagonism of this pathway led to impaired NFAT activity, d  ...[more]

Similar Datasets

Genomics Wnt/Ca2+/NFAT signaling maintains survival of Ph+ leukemia cells upon inhibition of Bcr-Abl
2010-07-15 | GSE21499 | GEO
Transcriptomics BCR-ABL triggers a glucose-dependent survival program during leukemogenesis through the suppression of TXNIP
2023-05-03 | GSE218451 | GEO
Genomics Identification of a novel lncRNA family that is required for efficient cellular transformation by Bcr-Abl oncogene
2019-04-17 | GSE119770 | GEO
Transcriptomics Gene expression profiling in BCR-ABL expressing LSCs and BCR-ABL-BLK expressing LSCs
2012-07-05 | E-GEOD-36096 | biostudies-arrayexpress
Transcriptomics Gene expression profiling in BCR-ABL expressing LSCs and BCR-ABL-BLK expressing LSCs
2012-07-06 | GSE36096 | GEO
Transcriptomics Imatinib therapy of chronic myeloid leukemia restores the expression levels of key genes for DNA damage and cell cycle progression
2014-01-01 | GSE33075 | GEO
Transcriptomics Charaterization of genetic alterations and gene expression signatures found in BCR-ABL inhibitor-resistant KCL-22 subpopulations and single clones
2014-10-07 | E-GEOD-62121 | biostudies-arrayexpress
Transcriptomics The differentially expressed genes profile upon HNRPDL silencing in K562 cells
2019-06-20 | GSE132975 | GEO
Transcriptomics The impact of a drug transporter ABCG2 haplotype in molecular response of chronic myelogenous leukemia patients is modulated by imatinib dose
2014-06-30 | E-GEOD-52107 | biostudies-arrayexpress
Transcriptomics Charaterization of genetic alterations and gene expression signatures found in BCR-ABL inhibitor-resistant KCL-22 subpopulations and single clones
2014-10-07 | GSE62121 | GEO