Selected aspects of redox metabolism in leukemogenesis

Blood cancers are caused by the accumulation of mutations in haematopoietic stem cells. This creates a malignant clone that has a selection advantage due to improved survival and unrestricted proliferation, a process of leukaemia development called leukemogenesis. Leukemogenesis is a complex process and it is difficult to identify a single mutation that is responsible for the transformation of haematopoietic cells. In addition to transcriptional deregulation caused by oncogenic fusion proteins, mutations in specific genes that regulate critical signaling pathways play a critical role in leukemogenesis. Examples of such genes include mutations in the isocitrate dehydrogenase 1 and 2 genes (mutIDH1/2). These genes are thought to play an important role in the development of leukaemia, as indicated by their increasing frequency in the progression of myelodysplastic syndrome to acute myeloid leukaemia. The functions of mutIDH1/2 include epigenetic regulation, changes in metabolism and redox homeostasis. It has been shown that regulation of reactive oxygen species (ROS) production and elimination, so-called redox homeostasis, is important for the proper function of haematopoietic stem cells and its disruption is a frequent phenomenon accompanying malignant transformation of these cells. Some mutations,..