09 July 2024

German scientists have released results from a major study that links genetic changes in multiple myeloma to the protein profile of the tumour cells.

Early results of the project have already led to the discovery of indicators that should help early detection of highly aggressive types of myeloma, as well as potential drug targets, the researchers say.

The Berlin-based researchers analysed genetic and molecular changes in a group of more than one hundred patients. They used mass spectrometry to map the protein profile of mutated plasma cells, and compared them with plasma cells from healthy people. This highlighted genetic alterations and changes in signalling pathways that led to uncontrolled activation of cancer cells.

Dr Philipp Mertins, head of the Proteomics technology platform of the Max Delbrück Center, Berlin, and one of the co-leaders of the study, said: “Genetic data alone is insufficient to explain the mechanisms involved in this disease. We wanted to know the consequences of genetic changes at the protein level and compare this molecular biology data against the actual course of the disease in patients.”

The discoveries included a protein profile that identifies cancers likely to take a particularly aggressive course, even in the absence of other risk factors.

The findings have been reported in Nature Cancer, and the researchers have created a free online tool to allow others to explore the data.

Researcher Dr Jan Krönke, of the Department of Haematology, Oncology and Cancer Immunology at Charité – Universitätsmedizin Berlin, and another study co-leader, said: “Our findings will help subcategorise patients more effectively going forward, personalising their treatment.

“We’ve identified key proteins and signalling pathways that can serve as the basis for even more effective, better tolerated treatments for multiple myeloma, for example for immune therapies such as CAR T-cell therapy.”

Source:

Ramberger E, Sapozhnikova V, Ng YLD, Dolnik A, Ziehm M, Popp O, Sträng E, Kull M, Grünschläger F, Krüger J, Benary M, Müller S, Gao X, Murgai A, Haji M, Schmidt A, Lutz R, Nogai A, Braune J, Laue D, Langer C, Khandanpour C, Bassermann F, Döhner H, Engelhardt M, Straka C, Hundemer M, Beule D, Haas S, Keller U, Einsele H, Bullinger L, Knop S, Mertins P, Krönke J.  (2024) “The proteogenomic landscape of multiple myeloma reveals insights into disease biology and therapeutic opportunities.” Nature Cancer, 28 Jun 2024, doi: 10.1038/s43018-024-00784-3

Link: https://www.nature.com/articles/s43018-024-00784-3

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