title: Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome: an iBFM-SG study.
abstract: Children with Down syndrome (DS) have a markedly increased risk of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). To identify chromosomal changes cooperating with +21 that may provide information on the pathogenesis of these leukemias, we analyzed 215 DS-ALLs and 189 DS-AMLs. Unlike previous smaller series, a significant proportion of DS-ALLs had the typical B-cell precursor ALL abnormalities high hyperdiploidy (HeH; 11%) and t(12;21)(p13;q22) (10%). The HeH DS-ALLs were characterized by gains of the same chromosomes as non-DS-HeH, suggesting the same etiology/pathogenesis. In addition, specific genetic subtypes of DS-ALL were suggested by the significant overrepresentation of cases with +X, t(8;14)(q11;q32), and del(9p). Unlike DS-ALL, the common translocations associated with non-DS-AML were rare in DS-AML, which instead were characterized by the frequent presence of dup(1q), del(6q), del(7p), dup(7q), +8, +11, del(16q), and +21. This series of DS leukemias-the largest to date-reveals that DS-ALL is a heterogeneous disorder that comprises both t(12;21) and HeH as well as DS-related abnormalities. Furthermore, this analysis confirms that DS-AML is a distinct entity, originating through other genetic pathways than do non-DS-AMLs, and suggests that unbalanced changes such as dup(1q), +8, and +21 are involved in the leukemogenic process.
authors.affiliation: Pediatrics Unit, Department of Clinical Sciences, University of Umeå, Umeå, Sweden. erik.forestier@pediatri.umu.se
authors.forename: Erik
authors.initials: E
authors.lastname: Forestier
authors.forename: Shai
authors.initials: S
authors.lastname: Izraeli
authors.forename: Berna
authors.initials: B
authors.lastname: Beverloo
authors.forename: Oskar
authors.initials: O
authors.lastname: Haas
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Kyra
authors.initials: K
authors.lastname: Michalová
authors.forename: Batia
authors.initials: B
authors.lastname: Stark
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
authors.forename: Andrea
authors.initials: A
authors.lastname: Teigler-Schlegel
authors.forename: Bertil
authors.initials: B
authors.lastname: Johansson
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations / Q000145:classification; D002877:Chromosomes, Human / Q000235:genetics; D003582:Cytogenetics; D004314:Down Syndrome / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*