2026-04-23 ゲーテ大学
Blood of a child with Down syndrome who is suffering from transient myeloproliferative syndrome (TAM). Under the microscope, similar to leukemia, almost exclusively the purple-stained immature precursors of white blood cells (blasts) can be seen. Photo: Jan-Henning Klusmann, Universitätsmedizin Frankfurt © Jan-Henning Klusmann
＜関連情報＞
- https://aktuelles.uni-frankfurt.de/english/unravelling-the-evolution-of-leukemia-in-children-with-down-syndrome/
- https://www.nature.com/articles/s41467-026-71707-2
ダウン症候群の骨髄性白血病における単一細胞転写進化 Single cell transcriptional evolution of myeloid leukemia of Down syndrome
Mi K. Trinh,Konstantin Schuschel,Hasan Issa,Rebecca Thomas,Conor Parks,Agnes Oszlanczi,Toochi Ogbonnah,Di Zhou,Lira Mamanova,Elena Prigmore,Emilia R. Robertson,Angus Hodder,Anna Wenger,Nathaniel D. Anderson,Holly J. Whitfield,Taryn D. Treger,José Gonçalves-Dias,Karin Straathof,David O’Connor,Matthew D. Young,Laura Jardine,Stuart Adams,Jan-Henning Klusmann,Jack Bartram & Sam Behjati
Nature Communications Published:23 April 2026
DOI:https://doi.org/10.1038/s41467-026-71707-2
Abstract
Children with Down syndrome have a 150-fold increased risk of developing myeloid leukaemia (ML-DS). Unusually for a childhood leukaemia, ML-DS arises from a preleukaemic state, termed transient abnormal myelopoiesis (TAM), via a conserved sequence of mutations. Here, we examine the relationship between the genetic and transcriptional evolution of ML-DS from natural variation; a rich collection of primary patient samples and foetal tissues with a range of constitutional karyotypes. We distil transcriptional consequences of each genetic step in ML-DS evolution, utilising single-cell mRNA sequencing, complemented by phylogenetic analyses in progressive disease. We find that transcriptional changes induced by the TAM-defining GATA1 mutations are retained in, and account for most of the ML-DS transcriptome. The GATA1 transcriptome pervades all stages of ML-DS, including progressive disease that had undergone genetic evolution. Our approach delineates the transcriptional evolution of ML-DS and provides an analytical blueprint for distiling consequences of mutations within their pathophysiological context.
