Myeloproliferative neoplasms (MPN) are a group of clonal, stem cell derived disorders of hematopoiesis associated with overproduction of one or more cell types in peripheral blood. We analyzed over 400 MPN patients for chromosomal aberrations using microarray technology. We found that 62.5% of the patients harbored at least one chromosomal aberration. Older patients had significantly more lesions than younger patients. The most significant association was observed between the number of genetic lesions in a patient and disease progression from chronic MPN to acute myeloid leukemia (AML). We found specific aberrations of chromosomes 1, 3, 5, 6, 7, 19 and 22 to be significantly associated with the transformation to AML. We were able to map target genes of recurrent chromosomal lesions including FOXP1, TET2, IKZF1, CUX1, ETV6 and RUNX1 on chromosomes 3p, 4q, 7p, 7q, 12p, and 21q, respectively. In a second project we complemented microarray technology with whole-exome sequencing. We performed a detailed analysis of chromosome 11 in MPN and other myeloid malignancies by analyzing over 800 patient samples. Uniparental disomies of chromosome 11 were associated with mutations in the CBL, MLL and DDB1 genes. A common deletion of chromosome 11p targeted the LMO2 transcription factor. Another frequently deleted region on chromosome 11p was significantly associated with de novo AML. The genetic basis of MPN appears to be complex. Interpretation of the data in a systems biology context has led to the identification of common mechanisms downstream of different lesions - a promising approach towards a better understanding of MPN pathogenesis.