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Researchers uncover mechanism that fuels growth of aggressive B-cell lymphoma

June 18, 2024
University of Helsinki
Researchers have discovered a molecular mechanism whose genetic disruption boosts the growth of the most common type of lymphoma.

Researchers from the University of Helsinki and HUS investigated the effects of recurring mutations in the KLHL6 gene in diffuse large B-cell lymphoma, the most common cancer of the lymphatic system.

The KLHL6 protein is part of a cellular system tasked with disposing of excess and unnecessary proteins. In many cancers, this system is disrupted, which advances malignant growth.

The researchers found that the KLHL6 protein breaks down the B-cell receptor and demonstrated that certain mutations lead to an increase in the number of these receptors.

"The B-cell receptor is an antibody on the surface of B-lymphocytes and a tool with which normal cells identify pathogens and fight against them. In corrupted cells, the B-cell receptor is activated in an anomalous manner, resulting in tissue growth and the development of lymphoma," says Doctoral Researcher Leo Meriranta, MD, from the University of Helsinki.

Absence of KLHL6 protein predicts poor treatment outcomes

In some of the cancer patients enrolled in the study, the KLHL6 protein was entirely absent from cells. Laboratory modelling revealed that the loss of KLHL6 in lymphoma cells increased the number of B-cell receptors manifold.

Professor of Oncology Sirpa Leppä, who heads the research group, emphasises the clinical significance of KLHL6.

"The lymphoma cases where the KLHL6 protein was absent were associated with a poor prognosis. The identification of pathogenic mechanisms relevant to these patients is particularly important for improving their prognoses through drug development," Leppä says.

Importance of therapy tailoring increasing

A British-American research group also reported similar findings simultaneously with the researchers from the University of Helsinki and HUS.

"The similar results obtained with different study designs are a solid indication that KLHL6 protein disruption plays a key role in some B-cell diseases," Meriranta says.

He emphasises that, in the future, treatment outcomes can be improved by targeting therapies on the basis of cancer biomarkers.

"The new findings open avenues to tailoring therapies, as the abnormal amount and activity of the B-cell receptor can be targeted pharmacologically. However, more research is still needed," Meriranta notes.

Diffuse large B-cell lymphoma

  • Every year, roughly 700 people in Finland develop diffuse large B-cell lymphoma.
  • The most common symptom is enlarged lymph nodes.
  • The disease is treated with immunochemotherapy, a combination of antibodies and cytostatic drugs.
  • In roughly one-third of the patients, the cancer is not cured and can be fatal.

Story Source:

Materials provided by University of Helsinki. Note: Content may be edited for style and length.

Journal Reference:

  1. Leo Meriranta, Selma Sorri, Kanutte Huse, Xiaonan Liu, Ivana Spasevska, Sadia Zafar, Iftekhar Chowdhury, Olli Dufva, Eerika Sahlberg, Luka Tandaric, Marja-Liisa Karjalainen-Lindsberg, Marko Hyytiainen, Markku Varjosalo, June H. Myklebust, Sirpa Leppa. Disruption of KLHL6 Fuels Oncogenic Antigen Receptor Signaling in B-cell Lymphoma. Blood Cancer Discovery, 2024; DOI: 10.1158/2643-3230.BCD-23-0182

Cite This Page:

University of Helsinki. "Researchers uncover mechanism that fuels growth of aggressive B-cell lymphoma." ScienceDaily. ScienceDaily, 18 June 2024. <>.
University of Helsinki. (2024, June 18). Researchers uncover mechanism that fuels growth of aggressive B-cell lymphoma. ScienceDaily. Retrieved July 14, 2024 from
University of Helsinki. "Researchers uncover mechanism that fuels growth of aggressive B-cell lymphoma." ScienceDaily. (accessed July 14, 2024).

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