iwCLL 2023 | Genomic stratification of patients with CLL
In this video, Anna Schuh, MD, PhD, University of Oxford, Oxford, UK, highlights the potential of whole-genome sequencing (WGS) to allow for stratification of patients with chronic lymphocytic leukemia (CLL) into distinct genomic subgroups, through an integrative genomic analysis using 186 genomic features. Using this approach, Dr Schuh and her team have determined that not all genomic subgroups are enriched for known driver mutations, and investigating these subgroups may provide a better understanding of global genomic changes and the value of non-coding regions in the disease. This interview took place at the biennial International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2023 meeting, held in Boston, MA.
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Transcript (edited for clarity)
As you know, earlier this year, we published a landmark analysis of almost 500 patients with chronic lymphocytic leukemia in need of treatment using whole genome sequencing, so there were almost a thousand genomes that were analyzed. The first authors of the paper are Pauline Robbe and Kate Ridout from my group. This was a pilot analysis for the Genomics England program and it demonstrates that whole genome sequencing has the potential to identify very clearly new subgroups of patients with chronic lymphocytic leukemia using very integrative genomic analysis...
As you know, earlier this year, we published a landmark analysis of almost 500 patients with chronic lymphocytic leukemia in need of treatment using whole genome sequencing, so there were almost a thousand genomes that were analyzed. The first authors of the paper are Pauline Robbe and Kate Ridout from my group. This was a pilot analysis for the Genomics England program and it demonstrates that whole genome sequencing has the potential to identify very clearly new subgroups of patients with chronic lymphocytic leukemia using very integrative genomic analysis. So using 186 different genomic features, we were able to cluster these patients into different groups with different clinical outcomes. Most of the patients had received chemo immunotherapy. We are now currently validating the analysis also for patients who’ve been treated in the FLAIR study with ibrutinib or a treatment. And the importance really of this, or the relevance of this paper, is that it shows that the genomic subgroups, although they’re enriched for known driver mutations such as trisomy or TP53, actually many patients within those subgroups do not have those driver mutations. And that allows us, for the first time, to cluster all patients into subgroups and to understand really a lot better the value of the non-coding regions in the genome, but also then the more global changes like telomere length, genomic complexity, the number of driver mutations, etc.
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