When blood cancer starts to spread

When blood cancer cells break through the bone and multiply, tumor cells become dangerously diverse and the immune response in the region changes, researchers from Berlin and Heidelberg report in Science Immunology. The detailed insights into cancer progression could advance diagnostics and treatment.

The incurable bone marrow cancer “multiple myeloma” often develops unnoticed in the bone marrow over decades. In advanced stages, lesions form that can destroy the bone and spread to other parts of the body. An interdisciplinary team from the Berlin Institute of Health at Charité (BIH), the Max Delbrück Center, the Queen Mary University of London's Precision Healthcare University Research Institute (PHURI), the Myeloma Center at Heidelberg University Hospital (UKHD), the University of Heidelberg and the German Cancer Research Center (DKFZ), together with other national and international partners, have been investigating what happens in these lesions when myeloma cells first break through the bone. The researchers discovered that the tumor cells diversify drastically when exiting the bone marrow, which also affects the immune cells in the cancer lesions. The new findings could contribute to more precise diagnostics and therapy, they report in “Science Immunology.”

When the tumor cells leave the bone, they find themselves in a completely different environment with different environmental conditions. “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,” says Dr. Niels Weinhold, head of Translational Myeloma Research at the UKHD's Department of Hematology, Oncology and Rheumatology.

Using innovative single-cell and spatial omics technologies, the team also examined for the first time how the immune system reacts to this “outbreak” of cancer cells from the bone. They discovered significant changes in the type and number of immune cells in the microenvironment of the cancerous lesions. For example, certain immune cells, known as T cells, had very different receptors and surface molecules in the foci outside the bone – a possible adaptation to the newly emerged heterogeneity of the tumor cells.

Uncovering the interaction between the immune system and cancer

“There seems to be a co-evolution between tumor and immune cells, in which both sides react to changes in the other,” says Professor Simon Haas, co-corresponding author of the study. He heads a lab in the joint focus area “Single-cell approaches for personalized medicine” at the BIH, Max Delbrück Center, and Charité – Universitätsmedizin Berlin. He is also chair for single cell technologies and precision medicine at PHURI. The researchers hypothesize that this intensified interaction between the immune system and the cancer may both promote and hinder the fight against the disease. The team is currently investigating which factors contribute positively or negatively to this interaction.

For their analyses, the international team used tissue samples that originated from myeloma lesions in various parts of the body. The material was obtained either by image-guided biopsies or during operations on fracture-prone or already broken bones. “Single-cell analysis and spatial multi-omics technologies enabled us to simultaneously investigate a wide range of properties of thousands of individual cells, taking into account their exact position in the tissue,” says Dr. Llorenç Solé Boldo, one of the first authors of the study.

The results could influence the diagnosis and therapy of myeloma in the future. Currently, samples for diagnosis are usually taken from the iliac crest (part of the pelvis) of patients. However, since the study has shown that cancer and immune cells in hotspots where the cancer cells break out of bone differ significantly from those in the iliac crest, these sites may be better suited for sample collection and allow a more precise assessment of the disease and possible adjustment of therapy.

Further information

Haas Lab

Focus area “Single cell approaches for personalized medicine”

PHURI

Literature

Alexandra Poos, Raphael Lutz, Lukas John, Llorenç Solé Boldo et al. (2025): “Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma.” Science Immunology, DOI: 10.1126/sciimmunol.adp6667

Max Delbrück Center

The Max Delbrück Center for Molecular Medicine in the Helmholtz Association (Max Delbrück Center) is one of the world’s leading biomedical research institutions. Max Delbrück, a Berlin native, was a Nobel laureate and one of the founders of molecular biology. At the locations in Berlin-Buch and Mitte, researchers from some 70 countries study human biology – investigating the foundations of life from its most elementary building blocks to systems-wide mechanisms. By understanding what regulates or disrupts the dynamic equilibrium of a cell, an organ, or the entire body, we can prevent diseases, diagnose them earlier, and stop their progression with tailored therapies. Patients should be able to benefit as soon as possible from basic research discoveries. This is why the Max Delbrück Center supports spin-off creation and participates in collaborative networks. It works in close partnership with Charité – Universitätsmedizin Berlin in the jointly-run Experimental and Clinical Research Center (ECRC), the Berlin Institute of Health (BIH) at Charité, and the German Center for Cardiovascular Research (DZHK). Founded in 1992, the Max Delbrück Center today employs 1,800 people and is 90 percent funded by the German federal government and 10 percent by the State of Berlin.