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Series GSE116256 Query DataSets for GSE116256
Status Public on Feb 28, 2019
Title Single-cell RNA-seq reveals AML hierarchies relevant to disease progression and immunity
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Other
Summary Acute myeloid leukemia (AML) is a heterogeneous disease that resides within a complex microenvironment, complicating efforts to understand how different cell types contribute to disease progression. We combined single-cell RNA sequencing and genotyping to profile 38,410 cells from 40 bone marrow aspirates, including 16 AML patients and five healthy donors. We then applied a machine learning classifier to distinguish a spectrum of malignant cell types whose abundances varied between patients and between subclones in the same tumor. Cell type compositions correlated with prototypic genetic lesions, including an association of FLT3-ITD with abundant progenitor-like cells. Primitive AML cells exhibited dysregulated transcriptional programs with co-expression of stemness and myeloid priming genes and had prognostic significance. Differentiated monocyte-like AML cells expressed diverse immunomodulatory genes and suppressed T cell activity in vitro. In conclusion, we provide single-cell technologies and an atlas of AML cell states, regulators, and markers with implications for precision medicine and immune therapies.
 
Overall design Bone marrow aspirates of five healthy control donors, 16 AML patients at diagnosis, and 19 matched samples during treatment were analyzed using Seq-Well single-cell RNA-sequencing (scRNA-seq). Acute myeloid leukemia (AML) patients in this study underwent standard induction chemotherapy between diagnosis (D0) and later time points (D14 and later). The only exception is AML328, who was treated with azacitidine + venetoclax. All 35 AML patient samples were also subjected to targeted amplification of known mutations in AML driver genes. One AML patient (AML921A) was analyzed in technical duplicate.
 
Contributor(s) van Galen P, Hovestadt V, Bernstein BE
Citation(s) 30827681
Submission date Jun 25, 2018
Last update date Mar 26, 2019
Contact name Peter van Galen
E-mail(s) petervangalen@gmail.com
Organization name MGH / Broad Institute
Department Pathology
Lab Dr. Bradley Bernstein
Street address 185 Cambridge Street
City Boston
State/province Massachusetts
ZIP/Postal code 02114
Country USA
 
Platforms (2)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL24106 MinION (Homo sapiens)
Samples (83)
GSM3587923 AML1012-D0
GSM3587924 AML1012-D0-anno
GSM3587925 AML210A-D0
Relations
BioProject PRJNA477870
SRA SRP183188

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Supplementary file Size Download File type/resource
GSE116256_RAW.tar 69.9 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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