Evaluation of role of growth arrest-specific protein 6 (Gas6) and its receptors Axl, Sky and Mer in acute myeloid leukemia (AML)

• Applicant: Professorin Dr. Sonja Loges
• Subject Area: Hematology, Oncology
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 237908678

Development of novel therapeutic strategies is urgently warranted in AML because with current therapies only a rather small fraction of patients can be cured. Elderly patients who constitute the majority of patients and whose numbers will further increase due to demographic change have a particular dismal prognosis. Interactions of AML cells with bone marrow stroma play an important role in AML pathobiology and therapy resistance. Thus it is crucial to investigate AML-stroma interaction in depth besides conducting leukemia cell-centered research.Our unpublished data indicate that the stroma-related protein growth arrest-specific protein 6 (Gas6) and its receptor Axl are involved in AML pathobiology and development of resistance against chemotherapy. Therefore, Gas6-Axl axis might represent a novel therapeutic target in AML. We could demonstrate that Axl expression is an independent prognostic factor in AML patients with normal cytogenetics (CN-AML). Therapeutic blockade of Axl blocks growth of AML cells in vitro and in vivo while leaving healthy hematopoietic cells not or much less affected. With the proposed project we intend to investigate therapeutic potential of inhibiting Gas6 and its receptors Axl, Sky and Mer (TAMR) in a pre-clinical AML model. Furthermore, we aim to dissect mechanisms and biological impact of Gas6-receptor interactions in AML in depth. Subsequently, data will be validated in human AML samples. In summary our goal is to generate a pre-clinical basis for translation of TAMR-inhibition to clinical studies.

• DFG Programme: Research Grants
• International Connection: Belgium
• Participating Person: Professor Peter Carmeliet, Ph.D.