The complexities of the multiple myeloma bone marrow microenvironment

Anna James Bott researches drug-resistance in multiple myeloma (MM) to try to understand the mechanism of action of novel therapeutics, with the aim of identifying drugable targets in MM. MM is an incurable cancer of plasma cells. It is an extremely heterogeneous disease; massive differences are seen between MM patients. Large variation is also seen within patients' own tissue such that sub-clonal structures of myeloma cells can be identified. Moreover, the surrounding bone marrow microenvironment (not just the myeloma cells) is critical for the development of MM. Therefore, applying single-cell techniques is fundamental to accurately capture the sub-clonal heterogenous populations in MM as well as the surrounding tumour microenvironment.

This image shows what happened when droplet-based single-cell techniques were applied to samples of bone marrow from myeloma patients treated with novel therapeutics and bioinformatic tools were implemented to analyse the resulting data. Each dot on the plot shown represents a cell. Clustering techniques, UMAP and tSNE (which use graph layout algorithms to visualise data in lower dimensional space), were used to separate cells into clusters based on similar gene expression profiles. Clusters are then annotated by cell type, for example myeloma cells, T cells, monocytes, red blood cells and so on. Differential expression analysis can then be performed for each cell type across treatment conditions to see how the novel therapeutics affect each cell type.

 Anna James-Bott is reading for a DPhil in Systems Approaches to Biomedical Sciences.