title: Uniparental disomy may be associated with microsatellite instability in acute myeloid leukemia (AML) with a normal karyotype.
abstract: The discovery of underlying genetic lesions helps to better understand the mechanisms of leukemogenesis and identify prognostic subgroups. Recent insights have allowed normal karyotype acute myeloid leukemia (AML) to be split into many molecular entities according to the genetic status of FLT3, NPM, CEBPA and MLL. Genome-wide single nucleotide polymorphism analysis was performed on 22 well-characterised AML patients with a normal karyotype. At the same time, microsatellite instability was investigated using a commonly used panel of polymorphic markers. Loss of heterozygosity (LOH) was found in 22.7% of cases without an associated copy number variation, suggesting that LOH represented an acquired partial uniparental disomy (aUPD) event. Three UPD+ cases harboured NPM mutations, associated with FLT3-ITD in two of them. An additional UPD patient had mutations both in CEBPA and in WT1. MSI was present at three loci in the three UPD+ cases (60%), whereas single locus MSI was present in three UPD- patients (17%). MSI involved the polymorphic PIG3 promoter in two UPD+ cases. It remains to be tested whether UPD and MSI association marks a common pathway of leukemogenesis.
authors.affiliation: Department of Haematology, Hospital de Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Serrano
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Carnicer
authors.forename: Vanesa
authors.initials: V
authors.lastname: Orantes
authors.forename: Camino
authors.initials: C
authors.lastname: Estivill
authors.forename: Adriana
authors.initials: A
authors.lastname: Lasa
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.forename: Anna M
authors.initials: AM
authors.lastname: Aventín
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
authors.forename: Josep F
authors.initials: JF
authors.lastname: Nomdedéu
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D018628:Gene Dosage; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D046228:Microarray Analysis; D053842:Microsatellite Instability; D009154:Mutation; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012074:Remission Induction; D024182:Uniparental Disomy / Q000235:genetics*; D025721:WT1 Proteins / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C497422:KMT2A protein, human; D009687:Nuclear Proteins; D025721:WT1 Proteins; D000090243:Nucleophosmin; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3