Frequency and prognostic implications of JAK 1-3 aberrations in Down syndrome acute lymphoblastic and myeloid leukemia.

Children with Down Syndrome (DS) have an increased risk of developing leukemia, including both acute myeloid (ML-DS) and acute lymphoblastic leukemia (DS ALL).1 These leukemias differ in clinical characteristics and biology from leukemias in non-DS children. ML-DS is characterized by a low diagnostic white blood cell (WBC) count, young age, FAB M7 morphology, excellent clinical outcome with survival rates of >90% and a high sensitivity to chemotherapy in vivo and in-vitro.1, 2 ML-DS is often preceded by transient leukemia (TL) in newborns, which in most cases resolves spontaneously. Approximately 20% of TL patients subsequently develop ML-DS.2 Both the TL and ML-DS blasts are characterized by mutations in the GATA-1 gene, a hematopoietic transcription factor, which result in a truncated protein GATA1s.3 Because these mutations occur both in TL and ML-DS, additional genetic abnormalities are needed in the progression from TL to ML-DS.