ArticleProceedings of the National Academy of Sciences of the United States of America2016
Stochastic modeling reveals an evolutionary mechanism underlying elevated rates of childhood leukemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Pediatric leukemia: origins, pathogenesis, the role of microenvironment and immunological modulation.Frontiers in immunology · 2026Review
- The aging hematopoietic stem cell niche: a mini review.Frontiers in hematology · 2025Article
- Targeting N-cadherin (CDH2) and the malignant bone marrow microenvironment in acute leukaemia.Expert reviews in molecular medicine · 2023Review
- Mutation signatures of pediatric acute myeloid leukemia and normal blood progenitors associated with differential patient outcomes.Blood cancer discovery · 2021Article
- Inflammation as a regulator of hematopoietic stem cell function in disease, aging, and clonal selection.The Journal of experimental medicine · 2021Review
- Increased risk of leukaemia in children with Down syndrome: a somatic evolutionary view.Expert reviews in molecular medicine · 2021Article
- Optimal experimental design for mathematical models of haematopoiesis.Journal of the Royal Society, Interface · 2021Article
- Mutation accumulation and developmental lineages in normal and Down syndrome human fetal haematopoiesis.Scientific reports · 2020Article
- A somatic evolutionary model of the dynamics of aneuploid cells during hematopoietic reconstitution.Scientific reports · 2020Article
- Quantifying local malignant adaptation in tissue-specific evolutionary trajectories by harnessing cancer's repeatability at the genetic level.Evolutionary applications · 2019Article
- Article
- Separating the Local and Malignant Dimensions of Cancer Adaptation.Cancer informatics · 2019Article
- From humans to hydra: patterns of cancer across the tree of life.Biological reviews of the Cambridge Philosophical Society · 2018Review
- Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly.Blood · 2017Article
- Hierarchical tissue organization as a general mechanism to limit the accumulation of somatic mutations.Nature communications · 2017Article
- Rejuvenation of aged hematopoietic stem cells.Seminars in hematology · 2017Review
- The evolution of lifespan and age-dependent cancer risk.Trends in cancer · 2016Article
- Aging of hematopoietic stem cells: DNA damage and mutations?Experimental hematology · 2016Review
- Should tissue structure suppress or amplify selection to minimize cancer risk?Biology direct · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Young children have higher rates of leukemia than young adults. This fact represents a fundamental conundrum, because hematopoietic cells in young children should have fewer mutations (including oncogenic ones) than such cells in adults. Here, we present the results of stochastic modeling of hematopoietic stem cell (HSC) clonal dynamics, which demonstrated that early HSC pools were permissive to clonal evolution driven by drift. We show that drift-driven clonal expansions cooperate with faster HSC cycling in young children to produce conditions that are permissive for accumulation of multiple driver mutations in a single cell. Later in life, clonal evolution was suppressed by stabilizing selection in the larger young adult pools, and it was driven by positive selection at advanced ages in the presence of microenvironmental decline. Overall, our results indicate that leukemogenesis is driven by distinct evolutionary forces in children and adults.
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Registered trials
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