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Series GSE53684 Query DataSets for GSE53684
Status Public on Apr 24, 2014
Title A mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia [array]
Organism Mus musculus
Experiment type Expression profiling by array
Summary The plasma cell transcription factor XBP1 is critical for terminal differentiation of B cells into plasma cells but has no known role at earlier stages of B-cell development. Here we show that XBP1 is not only important during early B-cell development and for survival of pre-B cells but also protects pre-B ALL cells. Among pre-B ALL subset, XBP1 was hypomethylated and highest expressed in the Ph+ ALL subset. Cre-mediated deletion of XBP1 in a mouse model of Ph+ ALL compromised proliferation and viability and prolonged survival of leukemia-bearing mice. Interestingly, XBP1 expression levels were positively transcriptionally regulated by STAT5 and negatively by BACH2 and BCL6. High XBP1 expression in high risk ALL patients at the time of diagnosis predicted poor outcome in two clinical trials. Clinically, small-molecule inhibition of IRE1-dependent XBP1-activation caused cell death of patient-derived pre-B ALL cells and affected leukemia-initiation in transplant recipient mice. Collectively, these studies identify XBP1 as an important survival factor and as a potential therapeutic target to overcome drug-resistance in pre-B ALL.
 
Overall design Genome-wide profiling of mRNA levels in BCR-ABL1 transduced murine Grp78 fl/fl pre-B cells with an empty vector (Grp78 wild type, MIG-1,2,3) and Cre  (Grp78 deletion, CRE-1,2,3).
 
Contributor(s) Masouleh BK, Geng H, Chang M, Muschen M
Citation(s) 24821775
Submission date Dec 27, 2013
Last update date May 04, 2018
Contact name Huimin Geng
E-mail huimin.geng@ucsf.edu
Organization name UCSF
Department Department of Laboratory Medicine
Street address 513 Parnassus Ave., MSB S-1480
City San Francisco
State/province CA
ZIP/Postal code 94143
Country USA
 
Platforms (1)
GPL8321 [Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array
Samples (6)
GSM1298807 BCR-ABL1 transformed murine ALL-like cells, Grp78 wild type, replicate 1
GSM1298808 BCR-ABL1 transformed murine ALL-like cells, Grp78 wild type, replicate 2
GSM1298809 BCR-ABL1 transformed murine ALL-like cells, Grp78 wild type, replicate 3
This SubSeries is part of SuperSeries:
GSE53685 A mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia
Relations
BioProject PRJNA232634

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Supplementary file Size Download File type/resource
GSE53684_RAW.tar 11.9 Mb (http)(custom) TAR (of CEL)
SRA Run SelectorHelp
Raw data provided as supplementary file
Processed data included within Sample table

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