Infections and autoimmunity: risk factors for [CFS] and subsequent B cell lymphoma and chronic lymphocytic leukemia development (planned study) Rosén

Funding announcement by the Swedish Cancer Society:

Infections and autoimmunity: risk factors for chronic fatigue syndrome and subsequent B cell lymphoma and chronic lymphocytic leukemia development

Anders Rosén
Linköping University, Sweden
2022

SEK 1 600 000
Diagnosis: lymphoma
Research area: preclinical research

https://www.cancerfonden.se/forskning/projekt/62bda998a7d6e40004146505

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"Background

Chronic bacterial and viral infections, such as pneumonia and glandular fever, can lead to the conversion of certain white blood cells into leukaemia cells. We are studying how this may be the starting point for chronic lymphocytic leukemia, CLL, and myalgic encephalomyelitis/chronic fatigue syndrome, ME/CFS. CLL arises from white blood cells called B lymphocytes, which produce so-called natural antibodies directed against microbes as well as their own cells called autoantigens. Infection + autoantibody formation is also seen in ME/CFS. We now know that several genetic defects exist, but we do not know how infections interact with these to cause disease development.

Description

We are studying basic molecular mechanisms in the development of CLL and ME/CFS, which confer an increased risk of B lymphoma. In B cells, various signals are generated from receptors such as membrane IgM, as well as DNA sensors. These interact to prevent the entry of bacteria and viruses e.g. into damaged mucosa or skin. In the case of long-lasting infections, which do not heal completely, B cells can start to multiply. But unfortunately, the risk of chromosome damage increases at the same time, because the inflamed environment of an infection contains harmful reactive oxygen radicals. These modify proteins, lipids and DNA, which can lead to autoimmunity and the risk of B malignancy.

Target

CLL is the most common type of leukaemia in adults. Every year, about 500 people are diagnosed in Sweden. Some patients can live for decades without treatment, while others develop more aggressive disease and die within a few years despite intensive treatment. There is currently no cure.
We want to elucidate the cellular drivers of CLL and ME/CFS. In particular, the importance of blocking the signals that drive cell growth, with a focus on signals from microbe-induced modifications. One possible strategy is to block multiple signals simultaneously and thereby prevent the growth of leukemia. We are participating in multicentre studies where these therapeutic approaches are tested clinically."