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Genomic and gene expression profiling in malignant hematology In the field of genomic and gene expression applications, associate professor Eigil Kjeldsen has been focusing his research on the clinical application of different types of microarray assays in malignant hematology. Microarrays are high throughput tools that have evolved during the past decade. These allow for dissection of all known genes in malignant cells at genomic or transcriptional level in a single experiment. The human genome contains approximately 23,000 protein-coding genes and more than 10,000 non-protein-coding genes (ncRNAs), such as microRNAs and long non-coding RNAs (lncRNA). At any given moment, each of our cells has some combination of genes turned on, while others are turned off. The combined expression of this magnitude of genes is affected by acquired chromosomal aberrations (e.g. translocations, inversions, deletions and amplifications) and by various mutations at the nucleotide level. The genetic abnormalities can result in different types of cancers including leukemias and malignant lymphoma. The genomic copy number changes can be examined at the gene resolution level using a highresolution oligo-based CancerCytohip in an assay known as array-based comparative genomic hybridization analysis (aCGH). We have examined more than 600 patients in a clinical setting using aCGH analysis of patients primarily enrolled in NOPHO or AML17 treatment protocols, in addition to several cancer cell lines. The purpose is to investigate the adjuvant effect of aCGH analysis in relation to conventional karyotyping and FISH analyses. Although molecular karyotyping by aCGH analysis is not commonly used in diagnostic clinical laboratories we find that it is a highly valuable adjunct to conventional cytogenetics, and in many instances it can uncover submicroscopic aberrations important for treatment and prognosis. MicroRNAs belong to a class of short ncRNAs, approximately 22 nucleotides in length that regulate the expression of other genes. It is known that a single miRNA can regulate the expression of up to several hundreds of protein-coding genes. Accumulating evidence during the past decade has revealed that microRNAs play important roles in controlling cellular functions, including cell differentiation, proliferation, and apoptosis and consequently confers critical roles in the initiation, progression, and relapse of various types of cancers, including leukemias. We examined miRNA expression profiles in patients with primary or secondary acute myeloid leukemias and in several leukemic cell lines. We correlated the expression profiles with genomic alterations identified by aCGH analysis to examine how genomic copy number changes affect miRNA expression at the global level. By these analyses we find that a general relation between copy number status and microRNA expression does not exist although specific microRNA expression signatures were uncovered. The perspective of the current research is to find ways to identify personalised genomic and microRNA expression signatures that can potentially translate into clinical therapeutics in malignant hematology.