ERIC 2020 | CLL at a genomic level
Catherine Wu, MD, Dana-Farber Cancer Institute, Boston, MA, discusses what we have learned about the chronic lymphocytic leukemia (CLL) genome. The CLL genome is very complex and heterogeneous with changes not only at a genetic level but transcriptomic as well. When treating CLL with immunotherapy, there is a different selective bottleneck which can be seen at an epigenetic level. However, now we have new tools to investigate genomic changes in leukemic cells. This interview took place during the European Research Initiative on CLL (ERIC) International Virtual Meeting 2020.
Transcript (edited for clarity)
I think that with each step, as we learn more and more about the CLL genome, we’re more and more convinced of how complex and heterogeneous it is that these changes are not only at the genetic level but also at the transcriptomic level. We described, what I described in my talk was I reviewed older studies that we have performed looking at the landscape of therapies for CLL and our findings with chemotherapy, with targeted inhibitors...
I think that with each step, as we learn more and more about the CLL genome, we’re more and more convinced of how complex and heterogeneous it is that these changes are not only at the genetic level but also at the transcriptomic level. We described, what I described in my talk was I reviewed older studies that we have performed looking at the landscape of therapies for CLL and our findings with chemotherapy, with targeted inhibitors. And I also reviewed a new study that we just reported out looking at stem cell transplant for CLL and looking at the changes that happen in the tumor cells with progression after transplant.
And so I think what that study really pointed out was two main points. I think one is that there is a very different type of selective pressure bottleneck that we see with immunotherapy than what we see with chemotherapy. And that’s reflected in the methylome changes in the epigenetic landscape thereafter. So I think that’s one thing that I talked about. And the other thing I talked about is that we have new tools that are available for us now that allow us to look at clonal heterogeneity with even greater resolution.
These are using barcoding strategies that allow us to at high-resolution track individual clones over time. This isn’t a model system, but it turns out the model system, the lessons that we learned are also appeared to be reflected in the patient samples as well. And it just basically underlines the stark ongoing diversification process that happens in leukemia cells naturally, but also under therapeutic pressure as well.
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Disclosures
Catherine Wu, MD, holds equity in BionTech, Inc; and receives research funding from Pharmacyclics.
