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Series GSE18673 Query DataSets for GSE18673
Status Public on Oct 22, 2009
Title TpoR Agonist signaling in AML primary cells
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Biologic characterization of SB-559457 (SB), a non-peptidyl hydrazone class of thrombopoietin receptor (Mpl) agonist, revealed toxicity towards human leukemia cells. Anti-proliferative effects followed by significant, non-apoptotic, cell death within 72 hours occurred in 24/26 AML, 0/6 ALL, and 3/6 CML patient samples exposed to SB, but not recombinant human thrombopoietin (rhTpo), in liquid suspension culture. Further investigation revealed increased phosphorylation of p70S6/S6 kinases in SB, but not in rhTpo, treated cells. Expression profiling of cells exposed to SB vs rhTpo revealed statistically significant, ~2-fold changes in GAPDH and REDD1 gene expression, confirmed by QRT-PCR. These genes, induced in energy or hypoxia stressed cells, have been implicated in cell death pathways, and may provide important clues to the mechanism of SB induced, leukemic cell death. These results suggest that nonpeptidyl, hydrazone class Mpl agonists may be clinically useful anti-leukemic agents by virtue of their combined thrombopoietic and anti-leukemic effects.
Overall design Primary cells collected from 5 patients with acute myeloid leukemia (AML) were stimulated stimulated with MPL receptor agonist (SB559457) or recombinant human Tpo (rhTpo) for 6 hours. Next, RNA was isolated from these cells. RNA was used for gene profile analyis to compare genes regulated in AML cells by SB559457 verus rhTpo. For each sample half of the cells were stimulated with Mpl agonist and half with rhTpo.
Citation(s) 19880492
Submission date Oct 21, 2009
Last update date Dec 06, 2018
Contact name Anna Kalota
Organization name University of Pennsylvania
Department Medicine, Hem/Onc
Street address 421 Curie Blvd
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
Platforms (1)
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (10)
GSM463910 AML332_6h_SB
GSM463911 AML332_6h_rhTpo
GSM463912 AML342_6h_SB
BioProject PRJNA121545

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
GSE18673_RAW.tar 18.3 Mb (http)(custom) TAR (of CEL, CHP)
Processed data included within Sample table
Processed data provided as supplementary file

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