title: Trisomy of chromosome 21 in leukemogenesis.
abstract: Extra copies of chromosome 21 are often found in sporadic leukemias. Constitutional trisomy 21 of Down syndrome (DS) is associated with markedly increased risk for childhood leukemia. Thus the oncogenic role of trisomy 21 in the more common sporadic childhood leukemias may be revealed through the investigations of the relatively rare leukemias of DS. Recent studies of the megakaryoblastic leukemias of Down syndrome have uncovered a developmental leukemogenic mechanism characterized by a unique pre-natal collaboration between overexpressed genes from chromosome 21 and an acquired mutation in the transcription factor GATA1. The base of the markedly enhanced risk for acute lymphoblastic leukemia conferred by trisomy 21 is still unclear. Studies of the leukemias of DS are likely to contribute to the general understanding of the oncogenic mechanisms of chromosomal aneuploidies, the most common abnormalities in cancer.
authors.affiliation: Research Section of Childhood Malignancies, Department of Pediatric Hemato-Oncology, and the Sheba Cancer Research Center, Sheba Medical Hospital, Tel-Hashomer, Ramat-Gan 52621, Israel. sizraeli@sheba.health.gov.il
authors.forename: Shai
authors.initials: S
authors.lastname: Izraeli
authors.forename: Liat
authors.initials: L
authors.lastname: Rainis
authors.forename: Libi
authors.initials: L
authors.lastname: Hertzberg
authors.forename: Gil
authors.initials: G
authors.lastname: Smooha
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Birger
mesh_terms: D002648:Child; D002891:Chromosomes, Human, Pair 21; D004314:Down Syndrome / Q000150:complications / Q000235:genetics; D006801:Humans; D007938:Leukemia / Q000209:etiology / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology / Q000235:genetics; D014314:Trisomy