ERIC CLL 2026 | Understanding the CLL genome: current knowledge and remaining gaps

I think what it concluded is that we have made very significant progress in describing the genome of CLL, both the coding, the non-coding genome, the epigenome, and then more recently Elias was talking about the insights that we are getting from single-cell studies, both primarily in Richter syndrome and in the evolution of later stages of CLL. So what we can probably conclude from this and what I think, if I understood him correctly, what he was trying to conclude was that we have a very good understanding now of all the coding mutations and the issue is that they are spread and there’s many different mutations and there’s a tremendous heterogeneity within the CLL genome. This is amplified further by changes in immunogenetics and in the immunoglobulin receptor rearrangements and the stereotyping of these rearrangements. And he showed very interesting data that would suggest that despite the fact that we can see at a single-cell level in different disease stages, we see oligoclonal subclones, very small subclones of CLL. They have different rearrangements, they have different mutations, but they still react in a very similar way to antigen exposure. And so similarly, maybe to what we observe in the clinic, is that patients, they don’t often progress or don’t always progress very gradually. They actually sometimes progress in bursts. And this made me very much think about those bursts, that the proliferation is driven by something common that different types of clones can still react to. And they basically expand, and then the patients go through a more stable phase again after that. So the conclusion of this is effectively that yes, CLL is a cancerous disease, is a genetic disease on the one hand, but it is very much influenced by the, or its progression is very much influenced by the environment and by some external factors. So, yeah, it’s a fascinating talk. I think we are at a point in time when we really need to team up the genomic people, the epigenomic people with the microenvironment people and of course also the T-cell immunologists because we need collective studies that systematically analyze both the genetic part of CLL and the immunological part of CLL in a very systematic way in the same samples in the same patients. So that would hopefully be the next step to further advance our understanding.

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