Mapping the cellular origin and early evolution of leukemia in Down syndrome
Elvin Wagenblast, Joana Araújo, Olga I. Gan, Sarah K. Cutting, Alex Murison, Gabriela Krivdova, Maria Azkanaz, Jessica McLeod, Sabrina Smith, Blaise Gratton, Sajid A. Marhon, Martino Gabra, Jessie J.F. Medeiros, Sanaz Manteghi, Jian Chen, Michelle Chan‐Seng‐Yue, Laura García‐Prat, Leonardo Salmena, Daniel D. De Carvalho, Sagi Abelson, Mohamed Abdelhaleem, Karen Chong, Maian Roifman, Patrick Shannon, Jean Wang, Johann Hitzler, David Chitayat, John E. Dick, Eric R. Lechman
Abstract
Down with leukemia Down syndrome is a congenital disorder caused by the trisomy of chromosome 21, and it is associated with a greatly increased risk of leukemia with origins in fetal development. Infants with Down syndrome are often born with a preleukemic condition, which later resolves in most cases. By using gene-edited human cells implanted into mouse models, Wagenblast et al. recapitulated the development of preleukemia and leukemia in the context of Down syndrome (see the Perspective by Roberts and Vyas). A specific mutation triggered a preleukemic condition in the context of trisomy 21 as expected, but progression to full-blown leukemia required a different genetic path and was not dependent on trisomy 21. Science , abf6202, this issue p. eabf6202 ; see also abj3957, p. 155