¹Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany

Correspondence: Dr C Schoch, Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, Munich 81377, Germany. Fax: +49 89 7095 4971; E-mail: claudia.schoch@med.uni-muenchen.de

Received 30 November 2004; Accepted 12 April 2005; Published online 19 May 2005.

Abstract

We performed microarray analyses in AML with trisomies 8 (n=12), 11 (n=7), 13 (n=7), monosomy 7 (n=9), and deletion 5q (n=7) as sole changes to investigate whether genomic gains and losses translate into altered expression levels of genes located in the affected chromosomal regions. Controls were 104 AML with normal karyotype. In subgroups with trisomy, the median expression of genes located on gained chromosomes was higher, while in AML with monosomy 7 and deletion 5q the median expression of genes located in deleted regions was lower. The 50 most differentially expressed genes, as compared to all other subtypes, were equally distributed over the genome in AML subgroups with trisomies. In contrast, 30 and 86% of the most differentially expressed genes characteristic for AML with 5q deletion and monosomy 7 are located on chromosomes 5 or 7. In conclusion, gain of whole chromosomes leads to overexpression of genes located on the respective chromosomes. Losses of larger regions of the genome translate into lower expression of the majority of genes represented by only one allele. The reduced expression of these genes is the most characteristic difference in gene expression profiles between AML with monosomy 7 and AML with deletion 5q, respectively, and other AML subtypes. Therefore, these data provide evidence that gene dosage effects gene expression in AML with unbalanced karyotype abnormalities. Losses of specific regions of the genome determine the gene expression profile more strongly than the gain of whole chromosomes.