о с т рый л е й к о з Haematopoietic development and leukaemia in Down syndrome Irene Roberts1 and Shai Izraeli2,3 1Paediatrics and Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; 2Childhood Leukaemia Research Unit, Department of Paediatric Haemato-Oncology, Cancer Research Centre, Sheba Medical Centre, Ramat Gan, Israel; 3 Department of human molecular genetics and biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Children with constitutional trisomy 21 (cT21, Down Syndrome, DS) are at a higher risk for both myeloid and B-lymphoid leukaemias. <...> TAM is caused by cooperation between cT21 and acquired somatic N-terminal truncating mutations in the key haematopoietic transcription factor GATA1. <...> As cT21 exists in all embryonic cells, the molecular basis of cT21-associated leukaemias probably reflects a complex interaction between deregulated gene expression in haematopoietic cells and the fetal haematopoietic microenvironment in DS. Keywords: trisomy 21, Down syndrome, acute lymphoblastic leukaemia, acute megakaryoblastic leukaemia, transient abnormal myelopoiesis, GATA1 C hildren with constitutional trisomy 21 (cT21, Down syndrome, DS) have a remarkably high risk of acute leukaemia [1]. <...> The incidence of acute myeloid leukaemia (known as ML-DS) is c. 150 times greater in young children with DS compared to children of the same age without DS while the incidence of acute B-cell lymphoblastic leukaemia (B-ALL) is c. 33 times higher [1, 2]. <...> Here we discuss recent insights into the natural history and pathogenesis of acute leukaemia in children with DS with the major emphasis on the perturbation of fetal and postnatal haematopoietic development by T21, that may render haematopoietic stem and progenitor cells (HSPC) more susceptible to leukaemic transformation. <...> DS-associated leukaemias – an overview As we wish to focus on the aspects of perinatal haematopoiesis that may predispose children with DS to leukaemia, we will only summarize the main features of the leukaemias of DS. Several recent reviews are recommended for more detailed description of the clinical features of these leukaemias [3, 5–9]. <...> Also, in a Correspondence: Professor Irene Roberts, Department <...>