OVER-MYR (EU406)

Multiple Myeloma (MM) is an incurable malignant plasma cell disease with an incidence of 5 per 100,000 inhabitants, and thus affecting approximately 25,000 new patients per year in the EU. MM has a debilitating impact on personal lives and health management . MM locates primarily to the bone marrow (BM). "Niches" within the bone marrow provide a microenvironment promoting tumor cell survival. In turn, multiple myeloma cells (MMC) transform the BM resulting in osteolytic lesions, anemia, and immunosuppression. The overall survival (OAS) of intensively treated patients below 65-70 is 8-9 years and the event free survival (EFS) is 3-4 years. Patients invariably relapse after each subsequent treatment line, become resistant to treatment, and succumb to their disease. On a molecular level, multiple myeloma is characterized by a distinct inter-patient heterogeneity as defined by interphase fluorescence in situ hybridization (iFISH), array-comparative genomic hybridization (aCGH) and gene expression based groups . At the same time, an intra-patient clonal heterogeneity is found, exemplified by the existing of subclones in iFISH.

The objectives of Over-MyR

1. To understand the mechanisms of drug resistance in MMC to 4 drugs (D, B, HDM, L) in current use
2. To elucidate the contribution of the tumor environment in conferring drug resistance in MM tumor cells
3. To identify novel compounds able to overcome resistance or revert it in MMCs to drugs in current use

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

Disciplines:Basic sciences, Biological sciences