Hidden complexity in blood cancer may hold key to better treatments
New research from Karolinska Institutet, published in Cell Reports Medicine, reveals that mantle cell lymphoma is more diverse than previously thought, highlighting the need for personalized therapies.
Researchers at Karolinska Institutet have discovered that mantle cell lymphoma (MCL), a rare and aggressive type of blood cancer, is already highly diverse at the time of diagnosis and continues to evolve in unique ways in each patient.
The research team used whole-genome sequencing and single-cell analyses to study tumor samples from patients both at diagnosis and after relapse. This allowed them to track how cancer cells change and adapt, especially when the disease returns following treatment.
“Our study shows that MCL is not a uniform disease. It consists of coexisting tumor cell populations with different genetic changes and cell states that shift over time and across tissues”, says Hui Wan, first author of the study and researcher in Prof. Pan-Hammarström’s lab at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
Could reduce the risk of relapse
One of the key findings in the study is that standard treatments may miss certain tumor clones, allowing the cancer to survive and come back. This highlights the importance of precision medicine, an approach that tailors treatment to the individual patient’s disease profile.
“By uncovering the genetic and cellular diversity of MCL, we hope to help doctors choose better treatment targets. This could improve therapy outcomes and reduce the risk of relapse”, says Prof. Pan-Hammarström.
The next step for the researchers is to study patients treated with newer therapies, such as BTK inhibitors and immunotherapies, and to validate their findings in larger patient groups. Their ultimate goal is to gain a deeper understanding of how relapses occur and how to prevent them.
Collaborations
The study was conducted in collaboration involving Birgitta Sander at Karolinska University Hospital, together with researchers from BGI, Mayo Clinic, Yale University, Uppsala university, and others.
Publication
"Tumor evolution and immune microenvironment dynamics in primary and relapsed mantle cell lymphoma",
Wan et al. Cell Reports Medicine, online 27 August 2025. Doi: 10.1016/j.xcrm.2025.102318.