STAT3 isoforms in acute myeloid leukemia

Many cancers are associated with aging, and leukemia as a cancer originating from blood stem cells, is strongly linked with age. Acute myeloid leukemia (AML) represents the second most common type of pediatric leukemia and the most common leukemia type in adults older than 50 years. With growing age also survival chances of patients decrease. One of the key signaling pathways in cancer development is the JAK/STAT pathway. Within this proposal we focus on two variants of one component of this pathway, namely STAT3, and their role during AML development. The expression of these STAT3 isoforms impacts on disease prognosis and may influence disease outcome. We aim to analyze the contribution of STAT3 isoforms to leukemogenesis with a particular focus on the underlying molecular mechanism. To do so we will use different experimental models of human and mouse tumorigenesis as well as state of the art in vitro experiments. We anticipate that our findings on the long run will help to improve clinical management, and that a deeper understanding of the molecular mechanisms of STAT3 isoform function in AML may pave the way for modern individualized treatment strategies of AML patients.

Acute myeloid leukemia (AML) is a severe form of blood cancer that occurs most frequently in older adults. The prognosis often worsens with age. This project investigated the role of two variants of the protein STAT3, a central component of the JAK/STAT signaling pathway, which regulates key processes in cancer development. Our research aimed to understand how these STAT3 variants influence AML onset and progression. We found that the shorter STAT3 variant has a protective function. In its absence, AML develops more aggressively in experimental models, accompanied by an activation of the interferon signaling pathway in the leukemic cells. These findings advance our understanding of the molecular mechanisms driving AML and highlight potential targets for therapeutic intervention. In particular, they suggest that modulating the interferon pathway could complement existing treatments, especially for patients expressing very low levels of the protective STAT3 variant in the leukemic cells.