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Series GSE138811 Query DataSets for GSE138811
Status Public on Oct 31, 2020
Title Leukemia-on-a-Chip: Dissecting the chemo-resistance mechanisms in B-cell acute lymphoblastic leukemia (B-ALL) bone marrow niche
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary B-cell acute lymphoblastic leukemia (B-ALL) blasts hijack the bone marrow (BM) microenvironment to form chemo-protective leukemic BM ‘niches’, facilitating chemo-resistance and, ultimately, disease relapse. However, the ability to dissect these evolving, complex interactions among distinct B-ALL subtypes and their varying BM niches is limited with current in vivo methods. Herein, we reconstituted an in vitro three-dimensional (3D) organotypic leukemic BM niche model using a ‘Leukemia-on-a-Chip’ platform and comparatively studied the spatial and genetic heterogeneity of the BM niche in regulating B-ALL chemotherapy resistance. By emulating the leukemia BM anatomy in vitro, we determined that the perivascular and endosteal niches, through providing cytokine (e.g. CXCL12) and adhesive (e.g. VCAM-1/OPN) signals, differentially enhance downstream leukemia-intrinsic NF-κB signaling to support B-ALL survival and regulate cell cycle-related signaling to promote dormancy, which following demonstrated the pre-clinical utility of this microphysiological system to screen concomitant niche-directed therapies. Furthermore, we revealed the heterogeneity across different B-ALL subtypes by mapping subtype-specific leukemia and niche signals with application of single-cell RNA sequencing and analysis, which may contribute to chemotherapy resistance and disease relapse. Together, these results validate that our Leukemia-on-a-Chip allows for real-time and controllable dissection of the dynamic and heterotypic interactions between leukemia blasts and their BM microenvironment, which may translate to personalized therapeutics screening and disease management.
Overall design Single-cell RNA-sequencing libraries of the retrived cells form the ex vivo human bone marrow niche models. Human REH B-ALL cells, Human SUP-B15, Human umbilical vein cells (HUVECs, Lonza), Human mesenchymal stem cells (hMSC, Lonza) and Human osteoblasts (hFOB 1.19, ATCC) were also sequenced as controls
Contributor(s) Witkowski MT, Dolgalev I, Aifantis I, Ma C, Chen W
Citation(s) 33127669, 37131801
Submission date Oct 14, 2019
Last update date Aug 02, 2023
Contact name Igor Dolgalev
Organization name NYU Grossman School of Medicine
Street address 550 1st Ave
City New York
State/province New York
ZIP/Postal code 10016
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (2)
GSM4119828 REH (B-ALL/Niche/B-ALL-Niche)
GSM4119829 SUP (B-ALL/Niche/B-ALL-Niche)
BioProject PRJNA577411
SRA SRP225514

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
GSE138811_RAW.tar 409.1 Mb (http)(custom) TAR (of MTX, TSV)
GSE138811_barcode_sample_metadata.txt.gz 822 b (ftp)(http) TXT
GSE138811_barcodes.tsv.gz 20.0 Mb (ftp)(http) TSV
GSE138811_counts.normalized.csv.gz 134.9 Mb (ftp)(http) CSV
GSE138811_counts.raw.csv.gz 46.5 Mb (ftp)(http) CSV
GSE138811_features.tsv.gz 297.6 Kb (ftp)(http) TSV
GSE138811_metadata.csv.gz 316.2 Kb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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