Growth dynamics in naturally progressing chronic lymphocytic leukaemia

Michaela Gruber, Ivana Bozic, Ignaty Leshchiner, Dimitri Livitz, Kristen Stevenson, Laura Rassenti, Daniel Rosebrock, Amaro Taylor-Weiner, Oriol Olive, Reaha Goyetche, Stacey M. Fernandes, Jing Sun, Chip Stewart, Alicia Wong, Carrie Cibulskis, Wandi Zhang, Johannes G. Reiter, Jeffrey M. Gerold, John G. Gribben, Kanti R. Rai, Michael J. Keating, Jennifer R. Brown, Donna Neuberg, Thomas J. Kipps, Martin A. Nowak, Gad Getz () and Catherine J. Wu ()
Additional contact information
Michaela Gruber: Dana-Farber Cancer Institute
Ivana Bozic: University of Washington
Ignaty Leshchiner: Broad Institute of MIT and Harvard
Dimitri Livitz: Broad Institute of MIT and Harvard
Kristen Stevenson: Dana Farber Cancer Institute
Laura Rassenti: University of California at San Diego Moores Cancer Center
Daniel Rosebrock: Broad Institute of MIT and Harvard
Amaro Taylor-Weiner: Broad Institute of MIT and Harvard
Oriol Olive: Dana-Farber Cancer Institute
Reaha Goyetche: Dana-Farber Cancer Institute
Stacey M. Fernandes: Dana-Farber Cancer Institute
Jing Sun: Dana-Farber Cancer Institute
Chip Stewart: Broad Institute of MIT and Harvard
Alicia Wong: Broad Institute of MIT and Harvard
Carrie Cibulskis: Broad Institute of MIT and Harvard
Wandi Zhang: Dana-Farber Cancer Institute
Johannes G. Reiter: Harvard University
Jeffrey M. Gerold: Harvard University
John G. Gribben: University of London
Kanti R. Rai: Hofstra North Shore-LIJ School of Medicine
Michael J. Keating: MD Anderson Cancer Center
Jennifer R. Brown: Dana-Farber Cancer Institute
Donna Neuberg: Dana Farber Cancer Institute
Thomas J. Kipps: University of California at San Diego Moores Cancer Center
Martin A. Nowak: Harvard University
Gad Getz: Broad Institute of MIT and Harvard
Catherine J. Wu: Dana-Farber Cancer Institute

Nature, 2019, vol. 570, issue 7762, 474-479

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-1252-x

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