information:classification
Blood cancers

Leukemia is 10 to 15 times more common in children with Down syndrome. In particular, acute lymphoblastic leukemia is 20 times more common and the megakaryoblastic form of acute myeloid leukemia (acute megakaryoblastic leukemia), is 500 times more common. Acute megakaryoblastic leukemia (AMKL) is a leukemia of megakaryoblasts, the precursors cells to megakaryocytes which form blood platelets. Acute lymphoblastic leukemia in Down syndrome accounts for 1–3% of all childhood cases of ALL. It occurs most often in those older than nine years or having a white blood cell count greater than 50,000 per microliter and is rare in those younger than one year old. ALL in Down syndrome tends to have poorer outcomes than other cases of ALL in people without Down syndrome. In short, the likelihood of developing acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) is higher in children with Down syndrome compared to those without Down syndrome.

Myeloid leukemia typically precedes Down syndrome and is accompanied by a condition known as transient abnormal myelopoiesis (TAM), which generally disrupts the differentiation of megakaryocytes and erythrocytes. In Down syndrome, AMKL is typically preceded by transient myeloproliferative disease (TMD), a disorder of blood cell production in which non-cancerous megakaryoblasts with a mutation in the GATA1 gene rapidly divide during the later period of pregnancy. GATA1 mutations combined with trisomy 21 contribute to a predisposition to TAM. In trisomy 21, the process of leukemogenesis starts in early fetal life, with genetic factors, including GATA1 mutations, contributing to the development of TAM on the preleukemic pathway. The condition affects 3–10% of babies with Down. While it often spontaneously resolves within three months of birth, it can cause serious blood, liver, or other complications. In about 10% of cases, TMD progresses to AMKL during the three months to five years following its resolution.