Mechanisms of RUNX1 regulation in human developmental haematopoiesis and childhood leukaemia

All adult blood cells are derived from prenatal blood stem cells produced in the embryo, where the process is dependent on a gene named RUNX1. Blood cell formation and the development of various blood cancers (leukaemia) are sensitive to RUNX1 levels.

In my DPhil, I will characterise the mechanisms regulating RUNX1 levels in normal and malignant human blood cell formation.

I will use a “test tube” experimental approach to model human fetal blood cell formation, by differentiating stem cells into immature blood cells (progenitors). I will characterize the dynamic regulatory changes in the RUNX1 genomic region at distinct blood progenitor stages.

These data will form the benchmark for the examination of RUNX1 regulation in primary human blood progenitor cells and childhood acute lymphoblastic leukaemia (ALL) samples.

Lastly, RUNX1 regulation will be perturbed through genetic and epigenetic engineering, to identify the contribution of aberrant RUNX1 expression to the development of childhood leukaemia.

This comparative approach will help us understand not only regulatory mechanisms of normal human blood cell formation, and how well this process can be modelled in a test tube, but also how altered regulation of RUNX1 affects leukaemia development.