Going the extra mile to understand chronic lymphocytic leukaemia | LC 25

Biography

Ivo Gut is the director of the Centro Nacional de Analysis Genomico, one of the largest genome analysis centers in Europe, and Group Leader of the Biomedical Genomics Group. Projects cover disease areas such as cancer, rare diseases, and immune-mediated diseases. He is also involved in genomics projects related to the Earth BioGenome project, author of more than 500 research articles, inventor of more than 20 patents or patent applications, and founder of four biotech start-ups.

Abstract

Chronic Lymphocytic Leukaemia (CLL) is the most common type of leukaemia in adults in Western countries. It is characterised by proliferative B lymphocytes. Genomic studies in the past two decades have provided a host of leads to make substantial headway towards the understanding of CLL and with it to improved treatment of patients suffering from this disease. Most recently, through the ERC-Synergy project BCLL@las, we have carried out an in-depth single-cell investigation into CLL. First, we created a single-cell atlas of a secondary lymphoid organ, the tonsils, which identified 121 distinct cell types, describing different cell states and providing a reference for immune cell annotation. Following on, we carried out single-cell analysis of patient progressions through the different stages of CLL. All our initial single-cell analysis was carried out using 10x Genomics Chromium single-cell RNA sequencing of either the 3´ or the 5´ of the transcripts and multiome analysis for epigenetic measures, surface protein markers and T and B cell repertoires were also included. However, the short sequence of the transcripts sequenced limits the ability to correlate known genomic features of the patient samples. Because of this, we recently started reanalysing our stored 10x libraries with Oxford Nanopore Technologies long-read sequencing. I will describe our observations and added information that becomes available from the application of Oxford Nanopore Technologies single-cell, long-read sequencing to capture the full length of transcripts in the context of the tonsil atlas and the transcript profiles of CLL patient cells carrying SF3B1 somatic gene mutations.