title: AML/MDS with 11q/MLL amplification show characteristic gene expression signature and interplay of DNA copy number changes.
abstract: AML/MDS patients carrying 11q amplifications involving the mixed lineage leukemia gene (MLL) locus are characterized by a complex aberrant karyotype (CAK) frequently including deletions within 5q, 17p, and 7q, older age and fast progression of the disease with extremely poor prognosis. MLL has been shown to be overexpressed in cases with 11q amplification. However, in most of the cases, the amplified region is not restricted to the MLL locus. In this study, we investigated 19 patients with AML/MDS and MLL gain/amplification. By means of array CGH performed in 12 patients, we were able to delineate the minimal deleted regions within 5q and 17p and identified three independent regions 11q/I-III that were amplified in all cases. Gene expression profiles established in 15 cases were used to identify candidate genes within these regions. Notably, analysis of our data suggests a correlation of loss of 5q and 17p and expression of genes present in 11q23-25. Furthermore, we demonstrate that the gene expression signature can be used to discriminate AML/MDS with MLL amplification from several other types of AML.
authors.affiliation: Department of Medical Genetics, Medical University of Vienna, Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zatkova
authors.forename: Sylvia
authors.initials: S
authors.lastname: Merk
authors.forename: Melanie
authors.initials: M
authors.lastname: Wendehack
authors.forename: Martin
authors.initials: M
authors.lastname: Bilban
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Muzik
authors.forename: Artur
authors.initials: A
authors.lastname: Muradyan
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Katharina
authors.initials: K
authors.lastname: Wimmer
authors.forename: Christa
authors.initials: C
authors.lastname: Fonatsch
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ullmann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051788:Myeloid-Lymphoid Leukemia Protein