Acute Megakaryoblastic leukemia in Down syndrome

Children with Down syndrome (DS) have a 10- to 20-fold increased risk of developing acute leukemia. An estimated 10% of newborns with DS develop Transient Myeloproliferative Disease (TMD) or Transient Leukemia (TL), a clonal accumulation of megakaryoblasts that resolves spontaneously within months. Acute megakaryoblastic leukemia (AMKL) develops in approximately 20% of cases of TMD/TL by 4 years of age. Both the blasts of AMKL and TMD/TL in DS harbor somatic mutations of GATA1, an essential transcriptional regulator of megakaryocytic differentiation. The distinct phenotypes of megakaryoblastic leukemia in DS are a unique biological model of the incremental process of leukeimic transformation.