Modelling childhood leukemia for the development of new and improved therapeutic approaches

Background: Leukaemia accounts for ~30% of all childhood cancers and ~20% of childhood cancer deaths, representing the most common pediatric cancer type and the second highest cause of cancer related death in children. Childhood leukaemia typically presents as either Acute Lymphoblastic Leukaemia (ALL) (80%) or Acute Myeloid Leukaemia (AML) (20%). Significant advances in disease understanding, enhanced prognostic classification and the use of intensive multi-agent chemotherapy in childhood ALL has led to superior 5-year survival rates of >90%. Survival rates in pediatric AML, however, remain significantly lower at only 60-70%, with nearly half of all children experiencing therapeutic refractory disease or relapse. Treatment options for relapsed or refractory AML are limited, with invasive bone marrow transplantation often the only possibility for cure. Project: The successful candidate will work within the Victorian Pediatric Cancer Consortium (VPCC) (https://vicpcc.org.au) to generate pre-clinical models of pediatric AML that faithfully recapitulate the human disease. These models will then be used to gain a deep understanding of the common mechanisms driving AML development in children, and identify novel therapeutically targetable functional dependencies in AML cells. Using the knowledge gained from this project, we aim to identify and develop new treatment approaches for childhood AML with reduced toxicity, enhanced efficacy and increased likelihood of long term remission and cure.