title: Genetic changes including gene copy number alterations and their relation to prognosis in childhood acute myeloid leukemia.
abstract: We studied a series of 68 subjects diagnosed with childhood acute myeloid leukemia (AML) using conventional cytogenetics and fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) to analyze mutations in FLT3 and NPM1 genes, and/or array comparative genomic hybridization (CGH). Cytogenetic/FISH abnormalities were observed in 71% of subjects, FLT3-ITD mutations in 15%, and NPM1 mutations in 13%. The array CGH alterations (average 3.6 per case) were observed in 96% of the tested subjects. The most frequent alterations were gains of 8q24.3 and 11p15.5-p15.4 in 16% of the samples. Six genes (AKT1, RUNX1, LTB, SDC1, RUNX1T1, and JAK2) from the imbalanced regions have been reported to be involved in AML, whereas other 30 cancer genes, not previously reported in an AML context, were identified as imbalanced. They probably correspond to non passenger alterations that cooperate with the recurrent translocations. The clinical data and genetic changes were tested to find out the possible association with prognosis. Genomic instability (four or more genomic imbalances) was correlated with poor patient outcome (p = 0.029).
authors.affiliation: Unit of Biological Anthropology, Department of Animal Biology, Plant Biology and Ecology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain. gemma.armengol@uab.cat
authors.forename: Gemma
authors.initials: G
authors.lastname: Armengol
authors.forename: Anna
authors.initials: A
authors.lastname: Canellas
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Alvarez
authors.forename: Pilar
authors.initials: P
authors.lastname: Bastida
authors.forename: José Sánchez De
authors.initials: JS
authors.lastname: Toledo
authors.forename: Maria Del Mar
authors.initials: Mdel M
authors.lastname: Pérez-Iribarne
authors.forename: Mireia
authors.initials: M
authors.lastname: Camós
authors.forename: Esperanza
authors.initials: E
authors.lastname: Tuset
authors.forename: Jesús
authors.initials: J
authors.lastname: Estella
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Coll
authors.forename: María Rosa
authors.initials: MR
authors.lastname: Caballín
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
mesh_terms: D000293:Adolescent; D001854:Bone Marrow Cells / Q000166:cytology; D002648:Child; D002675:Child, Preschool; D003582:Cytogenetics; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008297:Male; D009154:Mutation; D000090243:Nucleophosmin; D016133:Polymerase Chain Reaction; D011379:Prognosis; D014178:Translocation, Genetic