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

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

2010-07-15 | GSE21499 | GEO
2023-05-03 | GSE218451 | GEO
2019-04-17 | GSE119770 | GEO
2012-07-05 | E-GEOD-36096 | biostudies-arrayexpress
2012-07-06 | GSE36096 | GEO
2014-01-01 | GSE33075 | GEO
2014-10-07 | E-GEOD-62121 | biostudies-arrayexpress
2014-06-30 | E-GEOD-52107 | biostudies-arrayexpress
2019-06-20 | GSE132975 | GEO
2014-10-07 | GSE62121 | GEO