Immunogenetics and proteomics for improved, minimally-invasive early detection of lymphoid malignancies

Finding cancer on time to effectively intervene remains very challenging. In this thesis, Martijn Kolijn, a PhD student at the Erasmus MC and University Utrecht, has searched the blood to find abnormalities in genes and proteins associated with cancer. These abnormalities can be used like a fingerprint to recognize cancer, so people can receive the treatment they need at the right time. In the second chapter of his thesis, Martijn shows that chronic lymphocytic leukemia (CLL) can already be detected as early as 16 years prior to diagnosis, using a DNA sequencing technique that focuses on the B-cell receptor, an important driver in this disease. The development of cancer is a gradual process, marked by the sequential acquisition of genetic driver mutations. In chapter 3, Pieter Martijn shows which genetic driver events occur early during the development of this type of leukemia and which driver events are associated with rapid progression to overt disease. In chapter 4, we discover that the B-cell receptor displays remarkably consistent features among families with multiple siblings with CLL, reinforcing the concept of the B-cell receptor as an important driver. In chapter 5 and 6, we show that the potential for early detection through sequencing the B-cell receptor extends to lymphoma subtypes commonly observed in patients with autoimmune disorders and organ transplant recipients as well. Chapters 7, 8 and 9 explore various protein markers for lymphoma development and highlight the ways in which we can use computational models to better understand lymphoma development.