Predicting progression and survival in CLL
Prof Jonathan Strefford - University of Southampton, Southampton, UK
Could you please tell me a bit about your research into CLL?
Well we’re very interested in biomarkers and by biomarkers I mean things that help us manage the patient’s course of disease so we can predict how well a patient is going to do and what type of therapy might be most appropriate. We use genetics to try and do that because, of course, cancer is a genetic disease and the heterogeneity that we see clinically is mirrored by genetic heterogeneity and if we can understand that we can understand the clinical heterogeneity and perhaps help patients with the type of treatment and the type of management they might have.
So what results did you present at the conference?
At this conference we looked at the length of the telomeres and that is the end of the chromosomes. As a cell divides the telomere shortens as a normal course of cell division. But in tumour cells they can become very short and when they become very short fusions can occur between chromosomes and this can cause chromosomes to break up and the genome to become very unstable and you can imagine that that would be a bad thing to happen. What our research has shown is that that is indeed the case and patients with very short telomeres have a very poor prognosis. But what’s more important is if you flip it and you look at the patients with the long telomeres. You can identify a group of patients that do really, really well if they have very long telomeres and, of course, the hope is that you can give them the appropriate treatment and you can manage them in a way that reflects that more indolent course.
Were you looking at the telomeres circulating in the blood stream or from the tumour?
No, we were looking at… CLL cells do circulate in the blood so we were looking at blood cells but they were B-CLL cells. So we were looking at the tumour associated telomere length using a very simple quantitative PCR measurement. But what was very novel is that we were able to assess the relative power of telomere length compared to more established biomarkers and we were able to show that actually telomere length is a very powerful predictor and actually is more powerful than some of the biomarkers that we have historically considered to be important in the disease.
What plans do you have to take these findings and do further research?
One of the real problems with this was always that there are a number of things that have hindered implementation of telomere assessment into clinical care. One of them was really understanding their role in the context of clinical trials and that was one of the questions that we answered. That was very important because CLL is quite a heterogeneous disease and what clinical trials permit you to do is to get a more homogeneous population that has been treated in a consistent way. Now we need to replicate those studies, we need to validate the kind of cut-offs that are required and obviously, moving forward, we need to look at the relevance of telomere length in the context of the more modern therapies. But I do believe that it is an important… because there is this issue of there being hundreds of biomarkers in CLL and which ones are good and which ones are bad. Certainly our analysis suggests that telomere length is among the most important as far as its prognostic power. So we need to understand when to do it, how to do it, what the appropriate cut-offs are and then to ensure that we do it in the context of the new therapies.