Vladimír Divoký

The research group of the Department of Biology of the Faculty of Medicine and Dentistry focuses on discovering the pathogenesis of congenital and acquired hematopoietic disorders, especially myeloid malignancies; the aim is to understand the molecular basis of these diseases and to transfer the findings of basic and applied research into the development of new therapeutic approaches.

Malignant transformation of hematopoiesis is a multistep process, which involves accumulation of somatic mutations and a cascade of multiple cellular events. In addition, germline predisposing variants may interact with somatic events in leukemogenesis. Targeted therapy interfering with abnormal processes in leukemogenesis belongs to the most important challenges in leukemia research. The frame of our research is based on our earlier contributions to the understanding of cooperation between oncogene-induced DNA-damage response (DDR) and inflammatory cytokine network in leukemogenesis. We described DDR as a critical mechanism rate-limiting for malignant transformation by the hematopoietic oncogene, synergizing with inflammatory factors in checkpoint signaling and senescence, thereby counteracting leukemogenesis. In the case of myeloproliferative neoplasias (MPN), we elaborated on a concept of protection mechanisms that guard myeloproliferative progenitors from cell-intrinsic and cell-extrinsic DNA damage and thus DDR, facilitating creation of a barrier preventing cell cycle arrest, myelofibrosis and rapid malignant transformation. Currently, we test whether and how these processes can be targeted in preventing full leukemia transformation from different preleukemia disease states.