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Beyond the marrow: insights from comprehensive next-generation sequencing of extramedullary multiple myeloma tumors
T. Jelinek, D. Zihala, T. Sevcikova, A. Anilkumar Sithara, V. Kapustova, H. Sahinbegovic, O. Venglar, L. Muronova, L. Broskevicova, S. Nenarokov, D. Bilek, T. Popkova, H. Plonkova, J. Vrana, V. Zidlik, P. Hurnik, M. Havel, M. Hrdinka, Z. Chyra,...
Language English Country England, Great Britain
Document type Journal Article
Grant support
NU23-03-00374
Agentura Pro Zdravotnický Výzkum České Republiky (Czech Health Research Council)
No. CZ.02.1.01/0.0/0.0/16_019/0000868
EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj)
CZ.02.1.01/0.0/0.0/16_019/0000868
EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj)
MH CZ- DRO-FNOs/2020
Ministerstvo Zdravotnictví Ceské Republiky (Ministry of Health of the Czech Republic)
NLK
ProQuest Central
from 2000-01-01 to 1 year ago
Open Access Digital Library
from 1997-01-01
Nursing & Allied Health Database (ProQuest)
from 2000-01-01 to 1 year ago
Health & Medicine (ProQuest)
from 2000-01-01 to 1 year ago
Public Health Database (ProQuest)
from 2000-01-01 to 1 year ago
- MeSH
- Bone Marrow pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Multiple Myeloma * genetics pathology MeSH
- Mutation MeSH
- Biomarkers, Tumor genetics MeSH
- Tumor Microenvironment * genetics MeSH
- Prognosis MeSH
- Aged MeSH
- High-Throughput Nucleotide Sequencing * MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Extramedullary multiple myeloma (EMM) is an aggressive form of multiple myeloma (MM). This study represents the most comprehensive next-generation sequencing analysis of EMM tumors (N = 14) to date, uncovering key molecular features and describing the tumor microenvironment. We observed the co-occurrence of 1q21 gain/amplification and MAPK pathway mutations in 79% of EMM samples, suggesting that these are crucial mutational events in EMM development. We also demonstrated that patients with mutated KRAS and 1q21 gain/amplification at the time of diagnosis have a significantly higher risk of EMM development (HR = 2.4, p = 0.011) using data from a large CoMMpass dataset. We identified downregulation of CXCR4 and enhanced cell proliferation, along with reduced expression of therapeutic targets (CD38, SLAMF7, GPRC5D, FCRH5), potentially explaining diminished efficacy of immunotherapy. Conversely, we identified significantly upregulated EZH2 and CD70 as potential future therapeutic options. For the first time, we report on the tumor microenvironment of EMM, revealing CD8+ T cells and NK cells as predominant immune effector cells using single-cell sequencing. Finally, this is the first longitudinal study in EMM revealing the molecular changes from the time of diagnosis to EMM relapse.
Department of Biology and Ecology Faculty of Science University of Ostrava Ostrava Czech Republic
Department of Hematooncology Faculty of Medicine University of Ostrava Ostrava Czech Republic
Department of Hematooncology University Hospital Ostrava Ostrava Czech Republic
Department of Imaging Methods Faculty of Medicine University of Ostrava Ostrava Czech Republic
Department of Nuclear Medicine University Hospital Ostrava Ostrava Czech Republic
Department of Pathology University Hospital Ostrava Ostrava Czech Republic
School of Biological Sciences The University of Edinburgh Edinburgh EH9 3BF UK
References provided by Crossref.org
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