Cytogenetic and proteomic prognostic markers of CLL

Dr Lauren Thurgood - Flinders University, Adelaide, South Australia

My background is in proteomics, so I use proteomic techniques in CLL research. My main area of interest is looking at different cytogenetic subgroups in CLL. So we focus on del 13q, del 11q and patients who don’t have any cytogenetic aberrations but have mutated and unmutated IgVH genes and we try to analyse their protein expression differences between those subgroups using a relatively new technology which involves quantitative label-free mass spectrometry. We’ve been using that technology to try to identify differences in our survival pathways and protein expression within these patients.

The sort of work I’ve been presenting at the conference really is looking at metabolism differences between these patients as we seem to notice differences in the use of particular energy sources, so between carbohydrate use and lipid use. Our patients with the poor prognosis tend to be metabolising lipids preferentially over carbohydrate sources. So this work is fairly novel and it does allow us in the future to possibly identify some therapeutic targets where we could target the metabolism of the cells to try to induce their cell death in combination with already known therapies in CLL.

So specifically what results did you present today?

Today I presented some findings where we identified differential expression of various proteins within these subgroups. So, for example, there is a protein called macrophage inhibitory factor which we’ve found to be significantly down-regulated in a certain subset of patients that are doing quite well. So it’s suggesting that there’s an upregulation of this protein in our poor prognosis patients. The protein is being looked at a little bit in CLL but not from a therapeutic viewpoint. So it’s a possible avenue that we’re going to explore to see if we can exploit the expression of this protein in our patients who do quite poorly and if we can target it for increased survival in this group of patients.

So down the track what research have you got planned?

This research is going to move us more towards metabolomic-based research which hasn’t been carried out in any large detail in CLL. So we’re attempting some novel studies using metabolomic techniques such as chromatography and nuclear magnetic resonance, which is NMR, to try to find some small molecules that we might be able to inhibit to push these cells towards cell death as opposed to pro-survival.