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Series GSE108250 Query DataSets for GSE108250
Status Public on Feb 25, 2021
Title Modulating Bone Marrow Hematopoietic Lineage Potential to Prevent Breast Cancer Bone Metastasis
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The presence of disseminated tumor cells in patient bone marrow (BM) aspirates predicts decreased recurrence-free survival, yet little is known about whether hematopoietic BM cells impact bone metastases. Here, we report that the BM can be rendered metastasis-suppressive by the bone-targeting bisphosphonate, zoledronic acid (ZA). In particular, ZA modulates hematopoietic myeloid/osteoclast progenitor cell (M/OCP) lineage potential to render them metastasis-suppressive. Granulocyte-colony stimulating factor (G-CSF) promotes resistance to ZA by re-directing M/OCP differentiation. We identified BM transcriptional programs that associate with metastasis suppression and resistance to ZA. Analysis of patient blood samples taken at randomization revealed that women with plasma G-CSF levels >23 pg/mL experienced significantly worse outcome with adjuvant ZA than those on ZA who had lower plasma G-CSF levels. Our findings establish that hematopoietic cells and M/OCP lineage potential profoundly impact bone metastasis and support the discovery of biomarkers that stratify therapeutic responses in patients at risk of recurrence.
 
Overall design To test in murine bone marrow and osteoclast precursor cells the effects on gene expression of treatment with ZA and G-CSF. At least two replicates from each treatment were used (including no treatment and combination treatment) and analyzed in a pairwise fashion.
 
Contributor(s) Ubellacker J, Hutchinson J, McAllister S
Citation(s) 30065048
Submission date Dec 18, 2017
Last update date Feb 25, 2021
Contact name Jessalyn Ubellacker
E-mail(s) jubellacker@fas.harvard.edu
Organization name Harvard University
Lab Sandra McAllister Laboratory
Street address 4 Blackfan Circle
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (38)
GSM3142388 BOTH1: BM_RNASeq - Bone_Marrow Combined_treatment replicate_1
GSM3142389 BOTH3: BM_RNASeq - Bone_Marrow Combined_treatment replicate_3
GSM3142390 CTL1: BM_RNASeq - Bone_Marrow No_treatment replicate_1
Relations
BioProject PRJNA422921
SRA SRP126978

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
GSE108250_rawCounts_BMRNASeq.csv.gz 1.3 Mb (ftp)(http) CSV
GSE108250_rawcounts_OCPRNASeq.csv.gz 5.3 Mb (ftp)(http) CSV
GSE108250_tpm_BMRNBASeq.csv.gz 994.2 Kb (ftp)(http) CSV
GSE108250_tpm_OCPRNASeq.csv.gz 2.8 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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