NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE148520 Query DataSets for GSE148520
Status Public on Aug 06, 2021
Title Co-culture model of B-cell acute lymphoblastic leukemia recapitulates a transcription signature of chemotherapy-refractory minimal residual disease
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary B-cell acute lymphoblastic leukemia (ALL) develops when immature B cells stop differentiating and begin rapidly proliferating, allowing for an accumulation of immature cells in the bone marrow as well as the periphery. The bone marrow is a well-established sanctuary site, and while standard of care treatments allows for complete remission in most patients, a small population of patients will relapse, likely due to the presence of minimal residual disease (MRD) consisting of a dormant, chemotherapy-resistant cell population. We developed an in vitro cell culture model in which human ALL cells are grown in co-culture with either bone marrow-derived stromal cells or human osteoblasts. Within this culture, tumor cells can either be found in suspension, lightly attached to the top of the adherent cells, or buried under the adherent cells in a population that is phase dim (PD) by light microscopy. We have characterized the PD cells as being both a dormant and chemo-resistant cell population that relies heavily on glycolysis for energy. Additionally, we found that this model can be used to recapitulate MRD in vitro, as a means to identify and test novel therapeutics and treatment strategies that would allow for complete eradication of the disease from the bone marrow. In the current study, we characterized the transcriptional signature of the PD cells using RNA-Seq analysis, and this data was also compared to a published data set of human MRD B-ALL patients. Our RNA-Seq analyses showed that the PD cell population from the in vitro co-culture model closely mimics MRD expression patterns in patients. These findings suggest that our in vitro system can be used as a model for mimicking MRD. Furthermore, we identified both genes and key signaling pathways that were common between the PD cells and patient MRD that can provide us with potential therapeutic targets leading to a better outcome for the subset of patients that relapse.
 
Overall design REH (ATCC #CRL-8286) cell lines for ALL were grown in monoculture without bone marrow derived components (long term media culture, LTMC), co-cultured with Human osteoblasts (HOB) (PromoCell; Cat No: C-12720), or co-culutured with de-identified primary BMSCs (C2R). REH cells underneath HOB or BMSCs in co-culture (phase-dim under bright-field microscopy) were isolated (PMID: 26891147) and subjected to RNA-Seq analysis and compared to REH cultured alone.
 
Contributor(s) Rellick S, Hu G, Piktel D, Martin K, Geldenhuys W, Nair R, Gibson L
Citation(s) 34349149
Submission date Apr 12, 2020
Last update date Aug 06, 2021
Contact name Gangqing Hu
E-mail(s) michael.hu@hsc.wvu.edu
Organization name West Virginia University
Department MicroBiology, Immunology, and Cell Biology
Lab 2072A, HSC North, Floor 2
Street address 64 Medical Center Drive
City Morgantown
State/province West Virginia
ZIP/Postal code 26506-9177
Country USA
 
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (16)
GSM4473094 REH_alone_r3
GSM4473095 REH_alone_r4
GSM4473096 REH_alone_r1
Relations
BioProject PRJNA624866
SRA SRP256241

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
GSE148520_Laura_2020_processed_processed.xlsx 5.9 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap