Increased Mutagenesis During Fetal Hematopoietic Development In Down Syndrome

Children with Down syndrome are predisposed to leukemia during the first years of their life. 5-10% of newborns with Down syndrome are born with transient myeloproliferative disorder (TMD), which often spontaneously disappears. The majority of these patients achieves complete remission. However, in 20-30% of all TMD patients the disease progress in acute megakaryoblastic leukemia. In addition, they have a 20 fold higher risk of developing B-lymphocyte acute leukemia (B-ALL). Leukemic development in Down syndrome is initiated during fetal development. However, it is unclear why fetuses with a trisomy of chromosome 21 have an increased risk of developing leukemia.