A small group of tumour cells can eventually take control of Waldenström macroglobulinaemia. They gain an advantage over competing cell populations. Researchers from Clínic-IDIBAPS traced this process by analysing more than 130,000 individual cells from patients at different stages of the disease. The findings may help explain why some cases remain indolent while others progress and need treatment.
The study examined bone marrow and blood samples from people whose disease ranged from IgM monoclonal gammopathy of undetermined significance (IgM MGUS) to indolent and symptomatic Waldenström macroglobulinaemia. The results were published in HemaSphere. Carlos Fernández de Larrea, David F. Moreno and Ferran Nadeu coordinated the work within the Clínic Barcelona Comprehensive Cancer Centre and IDIBAPS.
The change can be seen in the tumour's structure. Early-stage disease contains several B-cell clones living alongside one another. In more advanced Waldenström macroglobulinaemia, one dominant tumour clone usually takes over.
This points to biological competition, rather than a single, uniform expansion from the beginning. Several cell populations coexist in the early stages. One of them can gain traits that improve its growth and survival, then become the basic driver of the disease. Clínic Barcelona described this clonal selection model as a central conclusion of the single-cell study.
The dominant cells showed more activity in genes and regulatory mechanisms linked to cell growth and survival. These molecular markers could help distinguish the clone gaining ground from other B cells. They may also clarify how the expansion takes place.
Genetic changes add another layer to the disease. Loss of part of chromosome 6 appeared more often in patients with higher-risk forms. This confirms an alteration previously linked to a less favourable clinical course. The analysis also confirmed characteristic mutations such as MYD88.
Some of these changes were already present in the early phases, before one cell population had become dominant. Genetic changes may so give selected clones an advantage without immediately producing the full clinical picture of symptomatic disease.
The tumour cells also interacted closely with their surroundings in the bone marrow. The strongest communication detected in the study was between dominant tumour cells and monocytes, immune cells involved in the body's response. The local immune environment is so part of the disease's development, not a passive backdrop.
Carlos Fernández de Larrea, David F. Moreno and Ferran Nadeu's team combined single-cell genomic and transcriptomic data with epigenetic information. This made it possible to track the diversity present at the start and show the biological advantages that later allow one clone to overtake the others.
The findings may improve patient classification and help shape future treatment strategies. The proposed markers and mechanisms still need to be tested in larger studies and independent cohorts. If the results are confirmed, single-cell profiling could help identify patients at greater risk of progressing to treatment and point to molecular targets for earlier intervention.
The study does not present a new therapy. Its basic contribution is a clearer map of how the disease changes, from a diverse group of cells to the dominance of a better-adapted tumour clone. That gives clinicians and researchers a more precise target for future work while keeping the evidence within its limits.
