BACKGROUND AND OBJECTIVES: Acute myeloid leukemia (AML) is a heterogeneous group of diseases. Patients with a normal karyotype constitute the largest single group; multiple chromosome rearrangements involving three or more chromosomes occur in 5 10% of AML patients. The pathophysiologic mechanisms underlying both groups are largely unknown. In the current study, we have systematically combined transcriptional profiles with cytogenetic data from 15 AML patients with either normal or complex karyotypes. DESIGN AND METHODS: The expression profiles were investigated by unsupervised hierarchical clustering, supervised cluster analysis, and comparative genomic microarray analysis. In addition, the samples were analyzed by G-banding and/or spectral karyotyping and comparative genomic hybridization. RESULTS: Our results show that AML with complex karyotypes exhibit a gene expression profile that is specific to this group of patients. The differentially expressed genes included several located on 5q and 7q, as well as genes involved in controlling cell division. We also found that DNA gains and losses caused by multiple chromosome rearrangements result in altered gene expression in a gene-dosage-dependent manner. INTERPRETATION AND CONCLUSIONS: These data provide insight into the mechanisms of multiple chromosome rearrangements and further demonstrate that the expression patterns of AML are strongly linked to the karyotypic status, even for the relatively undefined cytogenetic subgroup AML with complex karyotype.
BACKGROUND AND OBJECTIVES:Acute myeloid leukemia (AML) is a heterogeneous group of diseases. Patients with a normal karyotype constitute the largest single group; multiple chromosome rearrangements involving three or more chromosomes occur in 5 10% of AMLpatients. The pathophysiologic mechanisms underlying both groups are largely unknown. In the current study, we have systematically combined transcriptional profiles with cytogenetic data from 15 AMLpatients with either normal or complex karyotypes. DESIGN AND METHODS: The expression profiles were investigated by unsupervised hierarchical clustering, supervised cluster analysis, and comparative genomic microarray analysis. In addition, the samples were analyzed by G-banding and/or spectral karyotyping and comparative genomic hybridization. RESULTS: Our results show that AML with complex karyotypes exhibit a gene expression profile that is specific to this group of patients. The differentially expressed genes included several located on 5q and 7q, as well as genes involved in controlling cell division. We also found that DNA gains and losses caused by multiple chromosome rearrangements result in altered gene expression in a gene-dosage-dependent manner. INTERPRETATION AND CONCLUSIONS: These data provide insight into the mechanisms of multiple chromosome rearrangements and further demonstrate that the expression patterns of AML are strongly linked to the karyotypic status, even for the relatively undefined cytogenetic subgroup AML with complex karyotype.
Authors: Eric J Kort; Leslie Farber; Maria Tretiakova; David Petillo; Kyle A Furge; Ximing J Yang; Albert Cornelius; Bin T Teh Journal: Cancer Res Date: 2008-06-01 Impact factor: 12.701
Authors: Krzysztof Mrózek; Andrew J Carroll; Kati Maharry; Kathleen W Rao; Shivanand R Patil; Mark J Pettenati; Michael S Watson; Diane C Arthur; Ramana Tantravahi; Nyla A Heerema; Prasad R K Koduru; Annemarie W Block; Mazin B Qumsiyeh; Colin G Edwards; Lisa J Sterling; Kelsi B Holland; Clara D Bloomfield Journal: Int J Oncol Date: 2008-08 Impact factor: 5.650
Authors: Katleen De Preter; Roland Barriot; Frank Speleman; Jo Vandesompele; Yves Moreau Journal: Nucleic Acids Res Date: 2008-03-16 Impact factor: 16.971