An evolutionary journey across the CLL course
Ferran Nadeu
Fundació Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Chronic lymphocytic leukemia (CLL) is a malignancy of CD5+ B cells, the most common adult leukemia in Western countries, incurable, and characterized by a high biological and clinical heterogeneity. CLL is also a unique model that allows to study cancer from an evolutionary perspective. Increasing evidence suggests that CLL may originate from oligo- or multiclonal expansions, seeding multiple, potentially independent leukemic clones. Despite this initial diversity, most patients ultimately show dominance of a single clone, which drives disease progression and underlies the clinical diagnosis. After diagnosis, the clinical course varies widely. Some patients experience indolent, stable disease for years, whereas others show rapid progression requiring early treatment. In 5-10% of cases, CLL transforms into an aggressive lymphoma, usually diffuse large B-cell lymphoma, a process known as Richter transformation, conferring a dismal prognosis. This talk will explore how single cell genomics –including targeted single-cell DNA-seq, single-cell whole genome sequencing, and single-cell RNA-seq– provides new insights into the origin and evolutionary trajectories of CLL.