title: Biology and management of transient abnormal myelopoiesis (TAM) in children with Down syndrome.
abstract: Children with Down syndrome (DS) have an increased risk of Acute Myeloid Leukaemia (ML-DS), particularly megakaryoblastic leukaemia, which is clonally -related to the neonatal myeloproliferative syndrome, Transient Abnormal Myelopoiesis (TAM) unique to infants with DS. Molecular, biological, and clinical data indicate that TAM is initiated before birth when fetal liver haematopoietic cells trisomic for chromosome 21 acquire mutations in GATA1. TAM usually resolves spontaneously by 6 months; however 20-30% subsequently develop ML-DS harbouring the same GATA1 mutation(s). This review focuses on recent studies describing haematological, clinical and biological features of TAM and discusses approaches to diagnose, treat and monitor minimal residual disease in TAM. An important unanswered question is whether ML-DS is always preceded by TAM as it may be clinically and possibly haematologically 'silent'. We have briefly discussed the role of population-based screening for TAM and development of treatment strategies to eliminate the preleukaemic TAM clone, thereby preventing ML-DS.
authors.affiliation: Centre for Haematology, Imperial College London, United Kingdom.
authors.forename: Anindita
authors.initials: A
authors.lastname: Roy
authors.affiliation: Centre for Haematology, Imperial College London, United Kingdom. Electronic address: irene.roberts@imperial.ac.uk.
authors.forename: Irene
authors.initials: I
authors.lastname: Roberts
authors.affiliation: MRC Molecular Haematology Unit and Department of Haematology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom. Electronic address: paresh.vyas@imm.ox.ac.uk.
authors.forename: Paresh
authors.initials: P
authors.lastname: Vyas
mesh_terms: D001772:Blood Cell Count; D001773:Blood Cells / Q000473:pathology; D002648:Child; D002657:Child Development; D004314:Down Syndrome / Q000097:blood* / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007947:Leukemia, Megakaryoblastic, Acute / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D038042:Myelopoiesis; D009365:Neoplasm Regression, Spontaneous
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human