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Series GSE51033 Query DataSets for GSE51033
Status Public on Sep 20, 2013
Title Niche-based screening identifies small-molecule inhibitors of leukemia stem cells
Organism Mus musculus
Experiment type Expression profiling by array
Summary Efforts to develop more effective therapies for acute leukemia may benefit from high-throughput screening systems that reflect the complex physiology of the disease, including leukemia stem cells (LSCs) and supportive interactions with the bone-marrow microenvironment. The therapeutic targeting of LSCs is challenging because LSCs are highly similar to normal hematopoietic stem and progenitor cells (HSPCs) and are protected by stromal cells in vivo. We screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function. Among those that inhibited malignant cells but spared HSPCs was the cholesterol-lowering drug lovastatin. Lovastatin showed anti-LSC activity in vitro and in an in vivo bone marrow transplantation model. Mechanistic studies demonstrated that the effect was on-target, via inhibition of HMG-CoA reductase. These results suggest that statins should be re-evaluated as anti-leukemia agents, and illustrate the power of merging physiologically-relevant models with high-throughput screening.
Overall design Freshly isolated LSCe cells were treated with either 5µM BRD7116 or DMSO vehicle control for 6 hours in suspension in IMDM (12440053, Invitrogen), 10% FBS. Total RNA was extracted from the cells, labeled, and hybridized to MouseRef-8 v2.0 Expression BeadChips.
Hartwell, K.A. et al., In Press (full citation forthcoming)
Contributor(s) Hartwell KA, Miller PG, Mukherjee S, Kahn AR, Stewart AL, Logan DJ, Negri JM, Duvet M, Järås M, Puram R, Dancik V, AlShahrour F, Kindler T, Tothova Z, Chattopadhyay S, Hasaka T, Narayan R, Dai M, Huang C, Shterental S, Chu LP, Haydu JE, Shieh JH, Steensma DP, Munoz B, Bittker JA, Shamji AF, Clemons PA, Tolliday NJ, Carpenter AE, Gilliland DG, Stern AM, Moore MA, Scadden DT, Schreiber SL, Ebert BL, Golub TR
Citation(s) 24161946
Submission date Sep 20, 2013
Last update date Jun 14, 2018
Contact name Kimberly Hartwell
Organization name Broad Institute
Department Cancer Program
Street address 7 Cambridge Center
City Cambridge
State/province MA
ZIP/Postal code 02142
Country USA
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (7)
GSM1236379 LSC with BRD7116 for 6h_1
GSM1236380 LSC with BRD7116 for 6h_2
GSM1236381 LSC with BRD7116 for 6h_3
BioProject PRJNA219717

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
GSE51033_RAW.tar 3.1 Mb (http)(custom) TAR
GSE51033_non-normalized_data.txt.gz 1.2 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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