Microenvironmental determinants of Aplastic Anaemia progression to MDS / AML.

2019-2021 (Grant-in-Aid): Microenvironmental determinants of Aplastic Anaemia progression to MDS / AML. Associate Professor Rachel Koldej, ACRF Translational Research Laboratory, Melbourne Health.

Aplastic Anaemia is a disorder where the body stops producing enough new blood cells. Approximately 15% of Aplastic Anaemia patients are also at risk of progressing to Myelodysplasia or Acute Myeloid Leukaemia (MDS/AML) malignancy. This study aims to improve the identification of those Aplastic Anaemia patients most at risk of malignant disease progression as a first step towards the design of novel therapeutic interventions.    

Genetic mutations associated with MDS/AML are observed in almost half of Aplastic Anaemia patients, potentially putting them at risk of disease progression. However, most of these patients do not progress to Myelodysplasia or Acute Myeloid Leukaemia. This suggests other factors, (such as the bone marrow microenvironment) may also play a role in enabling or hindering disease progression. The goal of this application is to identify these additional factors involved; then determine how they impact patient disease outcomes.

Methodology includes the monitoring of bone marrow trephines from patients over time using Nanostring Digital Spatial Profiling, a new technology that allows both spatial protein and gene expression data to be tracked on single slide.

The results of this study will lead to improved biomarkers to monitor patient risk, plus potential identification of additional pathways involved in disease progression that may be targeted for therapeutic intervention.