학술논문

Growth dynamics in naturally progressing chronic lymphocytic leukaemia
Document Type
article
Source
Nature. 570(7762)
Subject
Biological Sciences
Biomedical and Clinical Sciences
Cardiovascular Medicine and Haematology
Oncology and Carcinogenesis
Clinical Research
Rare Diseases
Hematology
Cancer
Genetics
Lymphoma
Human Genome
2.1 Biological and endogenous factors
Aetiology
Cell Proliferation
Clone Cells
Cohort Studies
Disease Progression
Evolution
Molecular
Female
High-Throughput Nucleotide Sequencing
Humans
Leukemia
Lymphocytic
Chronic
B-Cell
Male
Neoplasm Recurrence
Local
Recurrence
Reproducibility of Results
General Science & Technology
Language
Abstract
How the genomic features of a patient's cancer relate to individual disease kinetics remains poorly understood. Here we used the indolent growth dynamics of chronic lymphocytic leukaemia (CLL) to analyse the growth rates and corresponding genomic patterns of leukaemia cells from 107 patients with CLL, spanning decades-long disease courses. We found that CLL commonly demonstrates not only exponential expansion but also logistic growth, which is sigmoidal and reaches a certain steady-state level. Each growth pattern was associated with marked differences in genetic composition, the pace of disease progression and the extent of clonal evolution. In a subset of patients, whose serial samples underwent next-generation sequencing, we found that dynamic changes in the disease course of CLL were shaped by the genetic events that were already present in the early slow-growing stages. Finally, by analysing the growth rates of subclones compared with their parental clones, we quantified the growth advantage conferred by putative CLL drivers in vivo.