Katarina Nilsson with Dr. Irene Ghobrial (DFCI)
Multiple myeloma is a blood cancer which involves the growth of abnormal plasma cells. Plasma cells secrete antibodies and are important in aiding the immune system to fight off infections. Overgrowth of these abnormal plasma cells in the bone marrow weakens the bone and inhibits the production of other blood cells. Unfortunately, multiple myeloma cannot be cured and has a poor prognosis. There are two important precursor states, monoclonal gammopathy of uncertain significance (MGUS) and smoldering multiple myeloma (SMM), which can progress to become multiple myeloma. In the Ghobrial Lab, we are examining the genetic and epigenetic factors that drive the precursor states into the cancerous multiple myeloma. While there is a lot of heterogeneity of tumors in multiple myeloma, we are specifically interested in better understanding the multiple myeloma cases that have a t(4,14) translocation, a chromosomal modification that lead to overexpression of an epigenetic modifier. This translocation is found in 15-20% of MM patients and associates with poor patient outcome. The focus of my project will be to use Hi-C and chromatin immuneprecipitation (HiChIP) on MM cell lines with and without the t(4,14) translocation. This study will provide us with the alterations of genome 3D structure that associate with the deregulation of gene expression profile in a t(4;14) cell, and trigger transformation of a healthy plasma cell to a tumor cell. Through this research, we will characterize the molecular mechanism of MM progression in patients with t(4;14) translocation.That could lead to identification of novel drug targets in the prevention or treatment of multiple myeloma.