Cancer Research

‘Engaging differentiation of immature leukemic cells in acute myeloid leukaemia’

Monash University, Vic.
Awarded 2016
Co-funded by the Rotary Club of Richmond, Victoria

“Blood cell production is organized in a hierarchical manner.”

Researcher Profile

Steven Ngo graduated from a Bachelor of Science (w Hons) undergraduate degree at the University of Melbourne in 2013. Steven completed his honours year at the Peter MacCallum Cancer Centre, where his project explored the developmental link between neural stem cells and the surrounding glial niche in Drosophila, and how this relationship could contribute to the development of neuroblastoma. Following his honours degree, Steven worked as a research assistant at the Centre of Eye Research Australia under Dr. Peter Van Wijngaarden in the Diabetic Retinopathy unit where his research largely focused on understanding the metabolic nature of the optic nerve and how this changes in diseases pertaining to the eye.

Having gained invaluable experience working in a range of research fields, Steven decided to undertake his PhD in a field of research that has always interested him greatly, focusing on haematopoietic stem cell/progenitor cell biology in the context of cancer.

Project Summary

Blood cell production is organized in a hierarchical manner. Broadly speaking, this hierarchy begins with haematopoietic stem cells, which possess the unique ability to self-renew, but to also differentiate and give rise to progenitor cells. In turn these progenitor cells, which are highly proliferative, will differentiate further and mature into different types of functional blood cells that are generally non-dividing.

In leukaemia’s such as acute myeloid leukaemia (AML), this tightly regulated process is disrupted through genetic mutations, resulting in the inability of progenitor cells to mature into specific cell types. Consequently, AML is characterised by an accumulation of highly proliferative, immature progenitor cells that fail to undergo the normal maturation process. AML is an aggressive cancer with 5-year survival rates of less than 50%. With this in mind, our research groups are investigating how particular mutations that control normal blood cell differentiation and maturation lead to AML. We have shown for the first time that reversing particular mutations drives the maturation and differentiation of leukemic cells and causes disease regression and remission.

This PhD project aims to develop a more comprehensive understanding of the underlying mechanisms that drive normal blood cell differentiation and maturation, and to identify novel ways to drive maturation of AML cells. Ultimately we hope that this Project will identify new therapeutic strategies for AML patients who are unresponsive to current therapies.

How will this research help people?

Each year thousands of people in Australia are diagnosed with leukemia, with the 5 year survival rate of patients that are diagnosed with the disease being alarmingly low. Although it is understood that leukaemia arises from a defect in blood cell lineage maturation, the specific underlying mechanisms that regulate blood cell development and thus the genetic mutations that drive leukaemogenesis are still largely unknown. This project provides the unique opportunity to use cutting edge genetic manipulation technology to tackle these important questions, and attempts to innovatively re-correct blood cell development. By forcing these highly proliferative leukemic cells to differentiate, the major cell populations driving leukaemogenesis are eliminated via a non-invasive approach. Therefore, this project has the potential to provide invaluable insight towards designing new therapeutic techniques in treating people with leukaemia.