EHA 2010 Annual Meeting, 10-13th June 2010, Barcelona
Dr Lars Bullinger (University of Ulm, Germany)
Use of genomics technologies in leukaemia research
My name is Lars Bullinger, I’m a haematologist, I’m a physician. I was trained in the University of Heidelberg and currently I’m working in Professor Döhner’s Department at the University of Ulm. This is a small university in the southern part of Germany but it’s one of the largest haematology departments in Germany. And my special interests are in translational research with regard to identifying new prognostically relevant microarrays in AML.
What genomics technologies are being used in leukaemia research?
Our mixed technologies or genomics technologies usually refer to the use of DNA microarrays. This technology has mainly been invented almost ten years ago and it was leukaemia where it first has been shown to be a powerful tool. Todd [??? 1:00] group first used it for diagnostic purposes, he could show that you can discriminate different leukaemia subtypes. And we also followed up on this, we could identify signatures that correlate with distinct molecular aberrations and cytogenetic aberrations. Currently this technology is also being developed to be used as a diagnostic tool.
You also can identify new subtypes with that that might be relevant with regard to improved leukemic therapy and recently there have also been advances that you can use microarrays to look for genomic aberrations. These are usually called array CGH or snip microarrays and these already have led to the identification of new tumour relevant genes like the TET2 gene that is involved in epigenetic deregulation of cells. And recently there have also been advances where you can use microarrays to directly profile epigenetic alterations.
Are there any microarrays specifically for acute myeloid leukaemia (AML)?
Not yet but there are several efforts to come up with a diagnostic platform. There is a spin-off company of the colleagues in Rotterdam for the Erasmus University which is called Skyline Diagnostics. They are currently developing a diagnostic platform which will be tested within a multi-centre treatment trial where we are also participating. The problem was with regard to coming up with platforms that could be correlated with outcome that the molecular markers we know in AML, there are so many new markers discovered within a short period of time that the signatures that they correlate with are older markers that are always out-dated very fast.
And the other thing is you of course need to validate your signatures within prospective clinical trials and that is what we are currently doing for our signature which we had generated for cytogenetically normal AML.
How will these developments relate to therapy for AML?
With regard to diagnostic platforms that might make the diagnosis just easier as you need some bone marrow plot and then it’s sufficient to isolate RNA1s, hybridise the chip and you will get information which you usually would need to do several tests which are all complicated and labour intense. So that might facilitate turn-around time to get the accurate diagnosis of the patient. And then these prognostic chips then hopefully will better help us to guide therapy.
Yes, over the last years we have learned that especially in PN1 mutations and CBB alpha mutations, those are two important genes, should be monitored up front and in addition prognosticly poor marker FLIP3, that’s a tyrosine kinase, and their mutations lead to poor response to chemotherapy and these are important with regard to new therapies as tyrosine kinase inhibitors are now coming away level to treat these patients.