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Hematopoietic stem cells ensure that our blood is constantly renewed and our immune system functions properly. These blood stem cells are found in the bone marrow and develop into various blood cells, such as red and white blood cells and platelets. In myeloproliferative neoplasms (MPN), a group of malignant bone marrow diseases, mutations in the stem cells lead to uncontrolled cell growth and ultimately to blood cancer. MPN primarily affects older adults and progresses slowly. Inflammatory processes play a central role in disease development in MPN patients and contribute to the deterioration of the patients state of health. A frequent mutation in the JAK2 gene further amplifies these inflammatory reactions. Another key player in inflammatory responses is a process called necroptosis. This process not only kills cancer cells but also triggers inflammation. Therefore, it is essential to investigate how these inflammatory signals drive MPN. We suspect that the signals triggered by JAK2 induce necroptosis, thereby intensifying further inflammatory reactions. We use the latest technologies and unique mouse models to test our hypotheses. Understanding the molecular mechanisms and the effects of altered necroptosis signals in MPN provides an entirely new perspective on the development and progression of this disease. Our research will enhance the understanding of how inflammation influences the progression of MPN and may potentially be controlled by drugs to combat the progression of MPN. This project could be pioneering new therapies against MPN and, in the long term, improve the quality of life for those affected.
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