title: The acute lymphoblastic leukemia of Down Syndrome - Genetics and pathogenesis.
abstract: Children with Down Syndrome (DS) are at markedly increased risk for acute lymphoblastic leukemia (ALL). The ALL is of B cell precursor (BCP) phenotype. T-ALL is only rarely diagnosed as well as infant leukemia. Gene expression profiling and cytogenetics suggest that DS-ALL is an heterogeneous disease. More than half of the leukemias are characterized by aberrant expression of the thymic stromal lymphopoietin (TSLP) receptor CRLF2 caused by genomic rearrangements. These rearrangements are often associated with somatic activating mutations in the receptors or in the downstream components of the JAK-STAT pathway. The activation of JAK-STAT pathway suggests that targeted therapy with JAK or downstream inhibitors may be effective for children with DS-ALL. The basis of the increased risk of BCP-ALL and in particular of the CRLF2 aberrations is presently unknown. Neither is it known which genes on the trisomic chromosome 21 are involved.
authors.affiliation: Functional Genomics and Leukemia Research, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Human Molecular Genetics and Biochemistry, Sackler Medical School, Tel Aviv University, Tel Aviv, Israel. Electronic address: sizraeli@sheba.health.gov.il.
authors.forename: Shai
authors.initials: S
authors.lastname: Izraeli
mesh_terms: D002869:Chromosome Aberrations; D004314:Down Syndrome / Q000150:complications* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000209:etiology*
keywords: Acute lymphoblastic leukemia; Down Syndrome