Monitoring chronic lymphocytic leukemia progression by whole genome sequencing reveals heterogeneous clonal evolution patterns
Menée sur trois patients atteints d'une leucémie lymphocytaire chronique, cette étude montre que la technique de séquençage du génome entier permet d'identifier des profils de mutations somatiques différents selon les patients et de suivre la progression de la maladie durant le traitement
Chronic lymphocytic leukaemia (CLL) is characterized by relapse after treatment and chemotherapy resistance. Like in other malignancies, leukaemia cells accumulate mutations during growth, forming heterogeneous cell populations that are subject to Darwinian selection and may respond differentially to treatment. There is therefore a clinical need to monitor changes in the subclonal composition of cancers during disease progression. Here, we use whole-genome sequencing (WGS) to track subclonal heterogeneity in three CLL patients subjected to repeated cycles of therapy. We reveal different somatic mutation profiles in each patient and use these to establish likely hierarchical patterns of subclonal evolution, to identify subclones that decline or expand over time, and to detect founder mutations. We show that clonal evolution patterns are heterogeneous in individual patients. We conclude that genome sequencing is a powerful and sensitive approach to monitor disease progression repeatedly at the molecular level. If applied to future clinical trials- this approach might eventually influence treatment strategies as a tool to individualise and direct cancer treatment.
Blood , résumé, 2012