Science and research

DNA Repair Systems in Myelodysplastic Syndromes

The damage of DNA repair mechanisms is one of the earliest manifestations of the initial stage of carcinogenesis. If DNA is not repaired, apoptotic mechanisms are initialized and it leads to programmed cell death. The pathogenesis of MDS has not been fully understood yet and it is assumed that MDS development is a multistage process, during which an accumulation of genetic and epigenetic changes occurs. Furthermore, the initial stages of MDS are characterized by increased apoptosis, which may reflect insufficient repair mechanisms.

We suppose that the increased number of different mutations detected in MDS is associated with impaired DNA repair mechanisms. Thus, we focuse on the detection of genomic changes localized in DNA repair genes that may contribute to the accumulation of genetic errors and promote the progression of malignant cells in MDS. These changes are detected at the level of genome, transcriptome and proteome in patients with MDS across all stages of the disease. Additionally, we identify single nucleotide polymorphisms (SNPs), which may determinate a predisposition to the disease.

At the functional level, we are going to investigate a reparation activity/capacity in primary MDS patient cells treated with DNA damage agent (neocarzinostatin). The data will provide complex insights into DNA repair mechanisms in MDS and may help to explain pathogenesis of this disease, which is characterized by progressive malignant transformation of mutated stem cells.

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Ústav hematologie a krevní transfuze
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