Transient Abnormal Myelopoiesis and AML in Down Syndrome: an Update.

Neha Bhatnagar,Paresh Vyas,Oliver Tunstall,Laure Nizery,Irene Roberts

doi:10.1007/s11899-016-0338-x

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.

Highlights

Population studies show that children with Down syndrome due to constitutional trisomy 21 have a markedly increased risk of developing acute leukaemia compared with children without Down syndrome [1]
myeloid leukaemia of Down syndrome (ML-DS) has a distinct natural history and clinical and biological features. It virtually always develops before the age of 5 years, and the acute leukaemia is preceded by a clonal neonatal preleukaemic syndrome known as transient abnormal myelopoiesis (TAM) that is unique to Down syndrome [3, 4]
In the Oxford Imperial Down Syndrome Cohort (OIDSC) Study, we addressed this question by prospectively classifying cases with blasts of >10 % and a GATA1 mutation in the first 14 days of life as TAM

Summary

Introduction

Population studies show that children with Down syndrome due to constitutional trisomy 21 have a markedly increased risk of developing acute leukaemia compared with children without Down syndrome [1]. Both myeloid leukaemia, known as myeloid leukaemia of Down syndrome (ML-DS), and acute lymphoblastic leukaemia are increased by 150- and ∼30-fold, respectively [1, 2]. ML-DS has a distinct natural history and clinical and biological features (reviewed in [3, 4]) It virtually always develops before the age of 5 years, and the acute leukaemia is preceded by a clonal neonatal preleukaemic syndrome known as transient abnormal myelopoiesis (TAM) that is unique to Down syndrome [3, 4]. Around 10–15 % of neonates with Down syndrome have a diagnosis of TAM with blasts >10 % and typical clinical fea-

This article is part of the Topical Collection on Myeloproliferative Disorders

Abnormal coagulation

Other TAM deaths

Conclusion

Findings

Compliance with Ethical Standards