title: Transient Abnormal Myelopoiesis and AML in Down Syndrome: an Update.
abstract: Children with constitutional trisomy 21 (Down syndrome (DS)) have a unique predisposition to develop myeloid leukaemia of Down syndrome (ML-DS). This disorder is preceded by a transient neonatal preleukaemic syndrome, transient abnormal myelopoiesis (TAM). TAM and ML-DS are caused by co-operation between trisomy 21, which itself perturbs fetal haematopoiesis and acquired mutations in the key haematopoietic transcription factor gene GATA1. These mutations are found in almost one third of DS neonates and are frequently clinically and haematologcially 'silent'. While the majority of cases of TAM undergo spontaneous remission, ∼10 % will progress to ML-DS by acquiring transforming mutations in additional oncogenes. Recent advances in the unique biological, cytogenetic and molecular characteristics of TAM and ML-DS are reviewed here.
authors: Children's Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 9DU, UK.
authors: Neha
authors: N
authors: Bhatnagar
authors: Paediatric Intensive Care Unit, Robert Debré Hospital, 48 Boulevard Sérurier, 75019, Paris, France.
authors: Laure
authors: L
authors: Nizery
authors: Bristol Royal Hospital for Children, Paul O'Gorman Building, Upper Maudlin St, Bristol, BS2 8B, UK.
authors: Oliver
authors: O
authors: Tunstall
authors: Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
authors: Paresh
authors: P
authors: Vyas
authors: Department of Paediatrics, Children's Hospital, University of Oxford, John Radcliffe Hospital, OX3 9DU, Oxford, UK. irene.roberts@paediatrics.ox.ac.uk.
authors: Irene
authors: I
authors: Roberts
mesh_terms: D004314:Down Syndrome / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000473:pathology* / Q000628:therapy; D007955:Leukemoid Reaction / Q000150:complications / Q000473:pathology* / Q000628:therapy; D012306:Risk; D033581:Stem Cell Transplantation
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human
keywords: Acute leukaemia; Down syndrome; Myeloproliferative disorders; Transient abnormal myelopoiesis