This grant is funded by the Multiple Myeloma Networking Group, the Central New Jersey Multiple Myeloma Support Group, and the Northern New Jersey Multiple Myeloma Support Group.
The overexpression of IgH enhancer/promoter driven genes such as cyclin D1, cyclin D3, or c-maf is likely to contribute to myeloma cell proliferation. Recent findings suggest an important role of histone methyltransferase MMSET (Multiple Myeloma SET domain protein) in malignant progression of myeloma. In about 15% of all myeloma cases, the t(4;14) translocation brings MMSET gene under the control of the µ enhancer followed by increased, as compared to healthy plasma cells, expression of the protein. It is not currently known how the increased expression of MMSET in plasma cells is translated into myeloma development and/or progression. Provided that MMSET acts as a transcriptional co-repressor and histone methyltransferase, Dr. Yurchenko and colleagues propose that the developmental program of normal and neoplastic plasma cells is regulated by this enzyme. Specifically, they hypothesize that deregulation of MMSET in plasma cells contributes to the disease initiation and/or progression. The goal of this research project is to establish the role of MMSET-dependent genetic program in normal plasma cell differentiation and myelomagenesis in mice. To achieve this goal, this project aims to define the role of MMSET in normal plasma and myeloma cell development and to identify the genetic network directly controlled by MMSET in B cells.