| Project ID: | AML-029 |
| Sample ID: | AML-029-17-1E |
| Submitted by: | NCBI (GEO) |
| Country: | USA |
| BioProject | PRJNA477870 |
| Sample name | NA |
| SRA accession: | SRP183188 |
| SRS accession: | SRS4319498 |
| SRX accession: | SRX5324529 |
| SRR accession: | SRR8521690 |
| GEO accession: | GSE116256 |
| Cancer type: | Acute Myeloid Leukemia |
| Cancer type abbreviation: | AML |
| Primary site: | Bone marrow |
| Tissue: | Bone marrow |
| Tumor grade: | NA |
| Tumor status: | NA |
| Donor age: | 58 |
| Donor gender: | Male |
| Treatment: | NA |
| Other metadata: | Bone marrow aspirate from AML patient |
| Project title: | Single-cell RNA-seq reveals AML hierarchies relevant to disease progression and immunity |
| Project abstract: | 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. |
| Construction protocol: | Bone marrow aspirates were viably frozen after using density gradient centrifugation to isolate mononuclear cells. Single-cell transcriptome analysis was performed using the Seq-Well method. Bone marrow aspirates were viably frozen after using density gradient centrifugation to isolate mononuclear cells. Single-cell transcriptome analysis was performed using the Seq-Well method. |
| Protocol: | Seq-Well |
| Instrument: | Illumina NextSeq 500 |
| Strategy: | RNA-Seq |
| Layout: | SINGLE |
| Publications: | P. van Galen et al., Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity. Cell, 2019, 176(6): 1265-1281 |
