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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,...

. 2024 ; 38 (6) : 1323-1333. [pub] 20240316

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24013747

Grantová podpora
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)

E-zdroje Online Plný text

NLK ProQuest Central od 2000-01-01 do Před 1 rokem
Open Access Digital Library od 1997-01-01
Nursing & Allied Health Database (ProQuest) od 2000-01-01 do Před 1 rokem
Health & Medicine (ProQuest) od 2000-01-01 do Před 1 rokem
Public Health Database (ProQuest) od 2000-01-01 do Před 1 rokem

Odkazy

PubMed 38493239
DOI 10.1038/s41375-024-02206-w
Knihovny.cz E-zdroje

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.

Citace poskytuje Crossref.org

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