Acute megakaryoblastic leukemia in Down syndrome.
Children with Down syndrome (DS) have a 10- to 20-fold increased risk of developing acute leukemia. An estimated 10% of newborns with DS develop Transient Myeloproliferative Disease (TMD) or Transient Leukemia (TL), a clonal accumulation of megakaryoblasts that resolves spontaneously within months. Acute megakaryoblastic leukemia (AMKL) develops in approximately 20% of cases of TMD/TL by 4 years of age. Both the blasts of AMKL and TMD/TL in DS harbor somatic mutations of GATA1, an essential transcriptional regulator of megakaryocytic differentiation. The distinct phenotypes of megakaryoblastic leukemia in DS are a unique biological model of the incremental process of leukemic transformation.
Hitzler
Johann K
JK
Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ont., Canada M5G 1X8. johann.hitzler@sickkids.da
D004314:Down Syndrome / Q000150:complications* / Q000628:therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007947:Leukemia, Megakaryoblastic, Acute / Q000209:etiology* / Q000628:therapy