The role of constitutively active JAK2 in hemopoietic malignancies and myeloproliferative disorders: Uncovering possible targets for future treatment strategies

• Applicant: Dr. Michaela Waibel
• Subject Area: Hematology, Oncology
• Term: from 2009 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 136356171

Hematopoiesis is a complex process driven by cytokines, their receptors and a family of non-receptor tyrosine kinases termed Janus kinases (JAKs). Active JAKs phosphorylate and activate downstream effectors including STATs (signal transducers and activators of transcription) and other signalling molecules. Constitutive activation of JAK2 in hematopoietic cells leads to their growth factor-independent proliferation and resistance to apoptosis. One example is the JAK2 V617F mutation observed in myeloproliferative diseases like polycythemia vera (PV), another one is the fusion of the oligomerization domain of the transcription factor TEL (ETV6) to the catalytic domain of JAK2 found in different leukemias. The goal of this project is to elucidate the so far largely unknown mechanisms that drive proliferation and apoptosis-resistance downstream of constitutively active JAK2 in lymphoid and myeloid cells expressing the TEL-JAK2 oncoprotein or the JAK2 V617F mutant. Microarray analysis and cell-based in vitro studies will be used to discover deregulated pro-proliferative and anti-apoptotic targets. Based on these results, novel treatment strategies will be developed and tested employing established and new chemotherapeutics in in vivo mouse models of JAK2-driven hematopoietic diseases.

• DFG Programme: Research Fellowships
• International Connection: Australia
• Host: Professor Dr. Ricky Johnstone