Study of resistance mechanisms in multiple myeloma (FWOKN257)

Multiple myeloma (MM) is an incurable malignant plasma cell disease localized in the bone marrow (BM, tumor environment). The environment is cruciall for the support of MM cell survival, proliferation, growth and development of drug resistance. New drugs have been identified that attack both MM cells and cells of the BM environment. Treatment of MM consists of chemotherapy (melphalan) and corticosteroids (dexamethasone) and new drugs such as proteasome inhibitors (bortezomib) and immune modular drugs (lenalidomide). Despite improvements in treatment, these drugs do not cure patients, and MM relapse repeatedly until the patient succumbs to the disease. Mechanisms of drug resistance, the expression of drug efflux transporters, induction of gene mutations and expression, adjustment mechanisms of apoptosis and tumor microenvironment induced resistance. The goal of this project is to induce resistance mechanisms in MM cells by clinically used substances and to investigate the BM microenvironment. The research project is divided into 3 work packages including:
- WP1: The role and regulation of ABCG2 expression in MM;
- WP2: Unraveling the bortezomib resistance mechanisms in multiple myeloma cells and the bone marrow microenvironment;
- WP3: The role of cereblon in the lenalidomide sensitivity in MM.
This research will lead to a better understanding of the disease and MM drugs resistance variance which can lead to improved treatment of MM patients.

Keywords:Blood, Stem Cell, Coagulation, Myeloma, Immunology, Microbiology, HLA, Hematology, Lymphoma, cancer, Bone Marrow Transplantation

Disciplines:Basic sciences, Biological sciences