Transient abnormal myelopoiesis in children with Down syndrome: a literature review and clinical case presentation

Down syndrome is a condition characterized by an extra copy of chromosome 21 resulting, among other things, in an increased susceptibility to blood disorders. Transient abnormal myelopoiesis is a unique phenomenon observed in neonates with Down syndrome. Typically, it presents in the neonatal period as a transient clonal expansion of blasts, often remaining clinically insignificant and undergoing spontaneous regression within the first 5 weeks of life. However, despite its transient nature, this condition should still be carefully monitored due to the high risk of its transformation into myeloid leukemia of Down syndrome which occurs in 20–30% of cases within the first 5 years of life. Acute myeloid leukemia and myeloid leukemia associated with Down syndrome arise from the same underlying genetic predisposition and are characterized by the proliferation of megakaryoblasts harboring a mutation in the GATA1 gene. Comprehensive assessment including morphology, immunophenotyping and cytogenetic and molecular genetic testing helps in differential diagnosis and facilitates therapeutic decision-making. Here, we present a literature review and report 2 clinical cases of transient abnormal myelopoiesis demonstrating the nature of this condition as well as its typical diagnostic features that enable prompt differential diagnosis and hence, timely initiation of supportive and cytoreductive therapy, while also highlighting the importance of careful monitoring in patients with Down syndrome.