This thesis describes investigations towards altered gene and miRNA regulation in paediatric acute myeloid leukaemia. The first part of the thesis focuses on altered gene regulation. High IGSF4 expression was typical for acute myeloid leukaemia patients with MLL-rearrangements and a FAB-M5 phenotype, and caused by promoter demethylation. RUNX1 mutations were found in 65% of congenital neutropenia patients and found in only 2.8% of de novo acute myeloid leukaemia patients. The second part of the thesis describes investigations towards epigenetic alterations in paediatric acute myeloid leukaemia, largely focusing on miRNA expression profiles and function. Acute myeloid leukaemia with MLL-rearrangements t(15;17), t(8;21) and inv(16) were found to have specific miRNA expression profiles. In addition, miR-9 appeared to be a tumour suppressor only in a t(8;21) acute myeloid leukaemia background. Mutations in epigenetic regulator genes were infrequently found in paediatric acute myeloid leukaemia.
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