Dataset Information

Proteogenomic landscape of multiple myeloma

ABSTRACT: Multiple myeloma is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, multiple myeloma remains incurable and better risk stratification as well as new therapies are therefore highly needed. The proteome of multiple myeloma has not been systematically assessed before and holds the potential to uncover additional insight into disease biology and improved prognostic models. Here, we provide a comprehensive multi-omics analysis including deep tandem mass tags (TMT)-based quantitative global (phospho)proteomics, RNA sequencing and nanopore DNA sequencing of 138 primary patient-derived plasma cell malignancies encompassing treatment-naive multiple myeloma patients treated in clinical trials, plasma cell leukemia, and the premalignancy monoclonal gammopathy of undetermined significance (MGUS), as well as healthy controls. We found that the (phospho)proteome of malignant plasma cells is highly deregulated as compared to healthy plasma cells and is both defined by chromosomal alterations and extensive post-transcriptional regulation. A protein signature was identified that is associated with aggressive disease and more predictive for outcome than cytogenetic-based risk assessment in newly diagnosed multiple myeloma. Integration with functional genetics and single-cell sequencing revealed generally and genetic subtype-specific deregulated proteins and pathways in plasma cell malignancies that include novel potential targets for (immuno)therapies. These findings provide new insights in the biology of multiple myeloma and will be a unique resource for investigating new therapeutic approaches.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Bone Marrow

DISEASE(S): Multiple Myeloma

SUBMITTER: Evelyn Ramberger

LAB HEAD: Philipp Mertins

PROVIDER: PXD038437 | Pride | 2024-07-09

REPOSITORIES: pride

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Dataset's files

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			Action	DRS
	20211115_experimentalDesignTemplate.txt	Txt
	Animal_20200729_ER_HStmtpro_myeloma_global_plex4_fr10.raw	Raw
	Animal_20200729_ER_HStmtpro_myeloma_global_plex4_fr11.raw	Raw
	Animal_20200729_ER_HStmtpro_myeloma_global_plex4_fr12.raw	Raw
	Animal_20200729_ER_HStmtpro_myeloma_global_plex4_fr13.raw	Raw

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The proteogenomic landscape of multiple myeloma reveals insights into disease biology and therapeutic opportunities.

Ramberger Evelyn E Sapozhnikova Valeriia V Ng Yuen Lam Dora YLD Dolnik Anna A Ziehm Matthias M Popp Oliver O Sträng Eric E Kull Miriam M Grünschläger Florian F Krüger Josefine J Benary Manuela M Müller Sina S Gao Xiang X Murgai Arunima A Haji Mohamed M Schmidt Annika A Lutz Raphael R Nogai Axel A Braune Jan J Laue Dominik D Langer Christian C Khandanpour Cyrus C Bassermann Florian F Döhner Hartmut H Engelhardt Monika M Straka Christian C Hundemer Michael M Beule Dieter D Haas Simon S Keller Ulrich U Einsele Hermann H Bullinger Lars L Knop Stefan S Mertins Philipp P Krönke Jan J

Nature cancer 20240628 8

Multiple myeloma (MM) is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, MM remains incurable, and better risk stratification as well as new therapies are therefore highly needed. The proteome of MM has not been systematically assessed before and holds the potential to uncover insight into disease biology and improved prognostication in addition to genetic and transcriptomic studies. Here we provide a comprehensive multiomics analysis including deep tandem mass tag-bas ...[more]

PMID: 38942927

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