The Genome-Wide Impact Of Trisomy 21 On Dna Methylation And Its Implications For Hematologic Malignancies

Children with Down syndrome (DS), caused by constitutive trisomy of chromosome 21, have a 20-fold increased risk of acute lymphoblastic leukemia (DS-ALL) and 500-fold increased risk of acute megakaryoblastic leukemia (DS-AMKL). At least 10-15% of DS neonates are born with the pre-leukemic syndrome transient abnormal myelopoiesis (TAM). Trisomy 21 affects hematopoiesis and leukemia risk; however, the underlying mechanisms are not fully understood. Previous small-scale studies (sample N<30) revealed genome-wide epigenetic effects of trisomy 21. We conducted a comprehensive and multi-ethnic study of neonatal DNA methylation in DS.