Molecular Mechanisms Wich Lead to Stroma-Indenpendente Growth of Myleom Cells.

Multiple Myeloma (MM) is a B-cel neoplasm, characterized by a clonal expansion of malignant plasma cells in the bone marrow (BM), which secrete a monoclonal immunoglobuline (Ig). Recently, a human MM cell line has been developed in our lab, starting from a long term BM culture from a MM patient. This MM 5.1 cell line exclusively grows in the presence of human BM stroma or in the presence of conditioned~nedium from normal BM cells. Moreover it was shown that the removal of the suoma induces apoptosis in the myeloma cells. Although IL-6 has been identified as the most important growth factor for myeloma cells, preliminary data show that the addition of exogeneous IL-6 does not take over the supportive role of the stroma. In a later stage, a MM variant of this cell line has been obtained (MM 5.2), which is characterized by a stroma-independent and a more aggressive proliferation. By using this unique model system, we aim to unravel the molecular mechanisms that lead to stroma-independent growth and extramedullary proliferation of the myeloma cells. Herefore, the stroma-dependent and the stroma-independent cell line will be compared for genetic differences.