? TRISOMY 21 Perturbed Haematopoiesis Fetal Liver Neonatal Childhood MICROENVIRONMENT GROWTH FACTORS/ CYTOKINES (IGF?) Perturbed Haematopoiesis ? MYELOPOIESIS Acquired GATA1 mutation(s) Expansion of HSC with MK/erythroid bias Expansion of MEP Increased megakaryocytes TRANSIENT ABNORMAL MYELOPOIESIS (TAM) MYELOID LEUKAEMIA OF DOWN SYNDROME (ML-DS) Additional genetic events Additional genetic events Reduced B progenitors (ELP-> PreproB block) Reduced B cells ACUTE LYMPHO-BLASTIC LEUKAEMIA LYMPHOPOIESIS Including CRLF2/JAK2 mutations TRISOMY 21