Project 459071

Multiple myeloma (MM) is a prevalent and incurable blood cancer with poor prognosis and a high rate of relapse. It presents a dire unmet need in its understanding as a disease and an urgency to improve outcomes through the pursuit of new treatment avenues. Studying MM with patient-derived cells is far superior and more biologically relevant compared to immortalized cell lines purchased from biological resource centres. However, this remains a challenge as current primary MM culturing techniques are incapable of maintaining cell viability for a duration long enough to conduct meaningful experiments. Therefore, it is crucial to urgently establish a new and effective protocol for keeping primary myeloma cells alive and to support their growth. Preliminary work has been conducted to identify the most relevant MM markers and to test various culture conditions with different growth media and environmental factors. The first aim is to determine which cytokines, substances secreted by some immune cells for cell signalling, are required for growth and survival by conducting a cytokine screen aided by a bioinformatic approach, which will then supplement the culture media. Results will be measured by growth, survival and retention of MM characteristics. In addition, the second aim is to conduct a small-molecule screen to further identify the compounds necessary to maintain MM cell viability and growth in vitro. Evaluation of the culture protocol from Aims 1/2 will be conducted in Aim 3, which is to apply these conditions in optimizing the culture of mouse model cells. This protocol must be simple, controllable, reproducible and compatible with high-throughput experiments to remove accessibility barriers experienced by researchers. Creation and establishment of such a protocol will aid the treatment of MM and provide possibilities for rapid development of novel and more specific therapies.