Characterisation of polyclonal IgG and paraprotein glycosylation in multiple myeloma to investigate structural and functional insights into stage-specific pathologies

Multiple myeloma is a type of blood cancer characterized by abnormal antibody called paraprotein, produced by the cancerous plasma cells in the bone marrow. Patients develop anaemia (due to bone marrow infiltration by cancerous cells), high calcium, bone destruction, kidney failure and death. Survival has improved since the approval of drugs such as lenalidomide and bortezomib. However, treatment resistance eventually develops and relapse occurs. This research investigates the myeloma paraprotein sugar structures called N-glycans. It is known that N-glycans on antibodies affect their function and binding to receptors on cells of the immune system. The project hypothesises that these sugar structures on the paraprotein are different across the spectrum of plasma cell disorders and especially between patients who are responders and non-nonresponders to anti-myeloma therapy. Furthermore, these linked sugar structures affect the binding of the paraprotein to its receptors. The understanding of the working and function of the paraprotein will further the development of drug therapy and benefit patients who have developed drug resistant. The identification of these N-glycans will aid in the development of potential biomarkers to improve diagnosis and monitoring for disease progression. In addition, this project also explores the question of why cancerous plasma cells do not undergo programmed cell death and how this relates to the binding of the paraprotein. Anti-myeloma therapy will no longer be one-size fits all approach, but rather a personalized treatment for patients.

Award Date
27 May 2016
Award Value
€249,857
Principal Investigator
Professor Giao Le
Host Institution
Dublin City University
Scheme
Research Training Fellowships for Healthcare Professionals