Increased risk of leukaemia in children with down syndrome: A somatic evolutionary view

K. A.L. Hasaart, E. J.M. Bertrums, F. Manders, B. F. Goemans, Ruben van Boxtel*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

3 Citations (Scopus)
2 Downloads (Pure)

Abstract

Children show a higher incidence of leukaemia compared with young adolescents, yet their cells are less damaged because of their young age. Children with Down syndrome (DS) have an even higher risk of developing leukaemia during the first years of life. The presence of a constitutive trisomy of chromosome 21 (T21) in DS acts as a genetic driver for leukaemia development, however, additional oncogenic mutations are required. Therefore, T21 provides the opportunity to better understand leukaemogenesis in children. Here, we describe the increased risk of leukaemia in DS during childhood from a somatic evolutionary view. According to this idea, cancer is caused by a variation in inheritable phenotypes within cell populations that are subjected to selective forces within the tissue context. We propose a model in which the increased risk of leukaemia in DS children derives from higher rates of mutation accumulation, already present during fetal development, which is further enhanced by changes in selection dynamics within the fetal liver niche. This model could possibly be used to understand the rate-limiting steps of leukaemogenesis early in life.

Original languageEnglish
Article numbere5
JournalExpert Reviews in Molecular Medicine
DOIs
Publication statusAccepted/In press - 19 Mar 2021

Bibliographical note

Publisher Copyright:
Copyright © The Author(s), 2021. Published by Cambridge University Press.

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