Myeloma cells diversify dramatically when they escape from the bone marrow, according to a major new study of the disease.
More than 30 researchers in Berlin and Heidelburg, Germany, and London, UK, worked together on the project to examine events within focal lesions, when the disease breaks out of the bone, using innovative single cell and spatial omics technologies.
Their findings point immediately to potential changes to the way the disease is monitored, they say.
The researchers suspect that the diversification of the cells enables them to adapt outside the bone marrow and to spread to other parts of the body.
The researchers also examined how the immune system reacted to the break-out of the cells. This showed significant changes to the type and number of immune cells in the microenvironment of the myeloma. T cells, they found, had a wide range of different receptors and surface molecules.
One immediate application is to suggest that myeloma samples during diagnosis and therapy should be taken from different sites to the standard location, the iliac crest of the pelvis. The cancer and immune cells in these locations differed significantly from those around the iliac crest, they found.
The findings have been reported in Science Immunology.
Joint study leader Professor Simon Haas, of the Max Delbrück Centre for Molecular Medicine, Berlin, said: “There seems to be a co-evolution between tumour and immune cells, in which both sides react to changes in the other.”
Fellow study leader Dr Niels Weinhold, of the Heidelberg University Hospital, said: “We suspect that this diversity helps the cancer cells adapt to survival outside the bone, enabling them to spread to other areas of the body.”
Source:
Lutz R, Poos AM, Solé-Boldo L, John L, Wagner J, Prokoph N, Baertsch MA, Vonficht D, Palit S, Brobeil A, Mechtersheimer G, Hildenbrand N, Hemmer S, Steiger S, Horn S, Pepke W, Spranz DM, Rehnitz C, Sant P, Mallm JP, Friedrich MJ, Reichert P, Huhn S, Trumpp A, Rippe K, Haghverdi L, Fröhling S, Müller-Tidow C, Hübschmann D, Goldschmidt H, Willimsky G, Sauer S, Raab MS, Haas S, Weinhold N. (2025) “Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma.” Science Immunology, 7 February 2025, doi: 10.1126/sciimmunol.adp6667.
Link: https://www.science.org/doi/10.1126/sciimmunol.adp6667
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