The one-carbon metabolism as novel therapeutic target in leukemia/lymphoma

B-cell malignancies are the most frequent blood cancers, arising from a type of white blood cell called B cells. Chronic Lymphocytic Leukemia (CLL) is the most common type of B-cell malignancy in adults, and is a slow-growing cancer. The progression of CLL is influenced by interactions with other non-cancerous cells in the surrounding environment. Despite advances in treatment, CLL remains an incurable disease that can transform into aggressive form.
The metabolism of cancer cells plays an important role in tumor growth and resistance to treatment. One-carbon (1C) metabolism is a metabolic pathway that provides the necessary building blocks for the growth of cancer cells. Targeting this pathway has shown some success in treating cancer, but the effectiveness of the treatment varies depending on the type of cancer and the surrounding environment.
We have found that genes involved in 1C metabolism are expressed differently in CLL cells compared to healthy B cells. We also discovered that targeting a specific enzyme in this pathway had a different effect depending on the types of B-cell malignancies, with CLL cells being highly sensitive. This suggests that understanding the metabolic processes in cancer cells could help identify new targets for treatment.
In this project, we plan to identify specific metabolic signatures related to 1C metabolism in different B-cell malignancies, both in the cancerous cells and the surrounding environment, particularly the cells of the immune system. We aim to develop new treatments to kill cancer cells and boost the body's own immune response, which could be used in B-cell malignancies including aggressive or refractory cases. We also ambition to identify biomarkers that can predict a patient's response to treatment. The ultimate goal is to develop personalized treatments that can be more effective in treating B-cell malignancies.