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| Status |
Public on Aug 18, 2021 |
| Title |
Subclone specific microenvironmental impact and drug response in refractory multiple myeloma revealed by single cell transcriptomics |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Virtually all patients with multiple myeloma become unresponsive to treatment over time. Relapsed/refractory multiple myeloma (RRMM) is accompanied by the clonal evolution of myeloma with heterogeneous genomic aberrations and profound changes of the bone marrow microenvironment (BME). However, the molecular mechanisms that drive drug resistance remain elusive. Here, we have analyzed the heterogeneous tumor cell population of 20 RRMM patients and its complex interaction network with the BME by single cell RNA-sequencing before/after treatment. Subclones with chromosome 1q-gain expressed a specific transcriptomic signature and frequently expanded during treatment. Furthermore, RRMM cells shaped an immune suppressive BME by upregulation of inflammatory cytokines and close interaction with the myeloid compartment. It was characterized by the accumulation of PD1+ γδ T-cells and tumor-associated macrophages as well as the depletion of hematopoietic progenitors. Thus, our study resolves transcriptional features of subclones in RRMM and mechanisms of microenvironmental reprogramming with implications for clinical decision-making.
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| Overall design |
Single cell RNA-seq of tumor cells and bone marrow microenvironment in relapsed/refractory multiple myeloma, **The submitter declares that the raw data were deposited to EGA (EGAS00001004805) due to data protection regulations.**
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| Contributor(s) |
Tirier SM, Steiger S, Mallm J, Poos A, Rippe K |
| Citation(s) |
34845188 |
| Submission date |
Nov 19, 2020 |
| Last update date |
Dec 01, 2021 |
| Contact name |
Karsten Rippe |
| E-mail(s) |
karsten.rippe@dkfz-heidelberg.de
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| Organization name |
German Cancer Research Center
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| Department |
Chromatin Networks
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| Street address |
Im Neuenheimer Feld 280
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| City |
Heidelberg |
| ZIP/Postal code |
69120 |
| Country |
Germany |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (87)
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| Relations |
| BioProject |
PRJNA679548 |
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