Transient Abnormal Myelopoiesis and AML in Down Syndrome: an Update

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.