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

Journal

Nature cancer

ISSN: 2662-1347

Titre abrégé: Nat Cancer

Pays: England

ID NLM: 101761119

Informations de publication

Date de publication:
28 Jun 2024

Historique:

received: 21 12 2022

accepted: 15 05 2024

medline: 29 6 2024

pubmed: 29 6 2024

entrez: 28 6 2024

Statut: aheadofprint

Résumé

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-based quantitative global (phospho)proteomics, RNA sequencing, and nanopore DNA sequencing of 138 primary patient-derived plasma cell malignancies encompassing treatment-naive MM, plasma cell leukemia and the premalignancy monoclonal gammopathy of undetermined significance, as well as healthy controls. We found that the (phospho)proteome of malignant plasma cells are highly deregulated as compared with healthy plasma cells and is both defined by chromosomal alterations as well as posttranscriptional regulation. A prognostic protein signature was identified that is associated with aggressive disease independent of established risk factors in MM. Integration with functional genetics and single-cell RNA sequencing revealed general and genetic subtype-specific deregulated proteins and pathways in plasma cell malignancies that include potential targets for (immuno)therapies. Our study demonstrates the potential of proteogenomics in cancer and provides an easily accessible resource for investigating protein regulation and new therapeutic approaches in MM.

Identifiants

DOI: 10.1038/s43018-024-00784-3 PMID: 38942927

pubmed: 38942927

doi: 10.1038/s43018-024-00784-3

pii: 10.1038/s43018-024-00784-3

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Subventions

Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)

ID : Emmy-Noether Program Kr3886/ 2-2 and SBF-1074

Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)

ID : 031L0220B

Informations de copyright

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