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Editorial
. 2013 Feb 15;12(4):533-4.
doi: 10.4161/cc.23667. Epub 2013 Jan 23.

The impact of trisomy 21 on early human hematopoiesis

Anindita Roy, Gillian Cowan, Paresh Vyas, Irene Roberts
Editorial

The impact of trisomy 21 on early human hematopoiesis

Anindita Roy et al. Cell Cycle. .
No abstract available

Keywords: Down syndrome; acute megakaryoblastic leukemia; fetal liver; hematopoiesis; neonatal leukemia; transient abnormal myelopoiesis; trisomy 21.

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Figures

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Figure 1. Impact of trisomy 21 on fetal and post-natal hematopoiesis. Schematic representation of molecular, biologic and clinical data, summarizing the effect of trisomy 21 (T21) on fetal, neonatal and childhood hematopoiesis. Fetal liver and, to a lesser extent, fetal bone marrow (BM) trisomic for chromosome 21 demonstrate perturbed hematopoiesis with an expansion of the hematopoietic stem cell compartment (HSC) and megakaryocyte-erythroid progenitors (MEP) and reduced B lymphopoiesis, even in the absence of GATA1 mutations. Interaction of hematopoietic cells with the T21 fetal liver and /or BM microenvironment may play a crucial role in initiating abnormal fetal hematopoiesis. Subsequent acquisition of GATA1 mutations in the abnormal/ expanded T21 fetal liver HSC and progenitors results in transient abnormal myelopoiesis (TAM) in late fetal/ neonatal life. Although most cases of TAM resolve spontaneously; in 15–30% of cases, additional genetic/ epigenetic events lead to Down syndrome-associated acute myeloid leukemia (ML-DS) before the age of 5 y. Abnormalities in hematopoiesis are likely to persist in childhood, but detailed systematic studies are necessary to establish this.
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Comment on

  • Roy A, Cowan G, Mead AJ, Filippi S, Bohn G, Chaidos A, et al. Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21. Proc Natl Acad Sci USA. 2012;109:17579–84. doi: 10.1073/pnas.1211405109. doi: 10.1073/pnas.1211405109

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