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AML/MDS with 11q/MLL amplification show characteristic gene expression signature and interplay of DNA copy number changes

MPG-Autoren

Wendehack,  Melanie
Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50438

Muradyan,  Artur
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50606

Ullmann,  Reinhard
Molecular Cytogenetics (Reinhard Ullmann), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Zitation

Zatkova, A., Merk, S., Wendehack, M., Bilban, M., Muzik, E. M., Muradyan, A., et al. (2009). AML/MDS with 11q/MLL amplification show characteristic gene expression signature and interplay of DNA copy number changes. Genes, Chromosomes and Cancer, 48(6), 510-520. doi:10.1002/gcc.20658.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0010-7D84-D
Zusammenfassung
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.