DNA methyltransferase 3B (DNMT3B) in multiple myeloma: a pivotal role in myeloma cell survival, drug resistance and disease progression?

Multiple myeloma (MM) is a rarely curable disease characterised by the accumulation of malignant plasma cells in the bone marrow. Although most MM patients initially respond well to the current therapies, there is a high chance of relapse after every round of treatment due to the development of drug resistance (DR).
This urges researchers to discover new targets to counter this DR. Next to genetic defects, it is now widely recognized that epigenetic defects also play a major role in MM, contributing to disease progression and high-risk disease. However, for most of the enzymes catalysing these epigenetic changes (the so-called epiplayers), their exact role in MM cell biology and DR has not yet been sufficiently explored. The HEIM research group recently found that one of the epiplayers, namely the de novo DNA methyltransferase 3B (DNMT3B), is upregulated in the malignant plasma cells of relapsed MM patients, indicating that DNMT3B could play an important role in DR and relapse in MM.

Therefore, I will here investigate the role of DNMT3B in MM cell survival, growth and drug response as well as its potential as a
1) predictive marker for drug response and
2) therapeutic target. In the short term this project will improve our understanding of the role of DNMT3B in DR in MM and by extension in cancer in general. In the long term it will help to design new, biomarker-driven personalized cancer therapies.