Deciphering the deregulated, complex transcription network in Down syndrome myeloid leukemia

Introduction: Children with Down syndrome (DS) have a high risk to develop myeloid leukemia (ML-DS) and antecedent transient abnormal myelopoiesis (TAM). Mutations in exon 2 of GATA1 (GATA1 s-mutations) are necessary and sufficient to induce TAM in synergy with trisomy 21. In contrast, Gata1 Δe2 (Gata1 s) mice crossed with Ts65dn mice, which are trisomic for ˜60% of the genes orthologous to human chromosome 21, do not recapitulate the human phenotype. Results: We investigated the oncogenic properties of GATA1 s in human fetal (with and without DS), neonatal and adult human hematopoietic stem and progenitor cells…