STAT3 isoforms in hematopoietic disorders

• Project number: LSC19-019
• Project duration: 36 months from 01.01.2021
• Project management: Dagmar Stoiber-Sakaguchi, Karl Landsteiner University for Health Sciences / Department of Pharmacology
• Project partners: Karl Landsteiner University for Health Sciences / Clinical Division of Internal Medicine 2 (University Hospital Krems), Medical University of Vienna / Department of Pharmacology

Background
Abnormal activation of the JAK/STAT (Janus kinase/signal transducer and activator of transcription) pathway is often associated with the development of cancer. Especially in blood cancers, prolonged activation of STAT transcription factors is often observed. One of these STATs, STAT3, regulates both proliferation and differentiation of cells. Since cancer is also associated with these two processes, STAT3 in particular has been described as an oncogene. STAT3 is expressed in two alternatively spliced isoforms, STAT3α and the truncated STAT3β isoform.
The aim of the present study is to analyse the contribution of these two STAT3 forms to leukaemogenesis. Therefore, we want to investigate how the STAT3β isoform acts as a tumour suppressor in acute myeloid leukaemia and whether such a tumour suppressive function of STAT3β is also found in other haematopoietic diseases such as myelodysplastic syndrome or multiple myeloma. Furthermore, it will be investigated whether the balance between the two isoforms can help to predict the further course of the disease in patients. It is expected that the present study will elucidate the function and role of the shorter STAT3β isoform as well as the STAT3-dependent control of leukocytes.