Examining the interaction of leukaemia stem cells with the microenvironment to identify targeted therapeutics in Acute myeloid leukaemia.

Overview

Acute myeloid leukaemia (AML) has a low survival rate of 22% in Aotearoa/New Zealand. Understanding the pathology of AML-associated gene mutations is required to develop effective therapies. The haematopoietic microenvironment or niche plays an important role in sustaining pre-leukemic and leukemic stem cells. Leukemic cells express genes encoding adhesion and extracellular matrix proteins, which promote niche lodging, survival, and treatment resistance. Hijacking of the niche by leukemic cells is emerging as an important determinant of treatment response in haematopoietic malignancies. Mutations in genes encoding the cohesin complex are present in ~12-50% of myeloid malignancies. We found that cohesin mutations in human leukaemia cell lines and zebrafish enhance expression of cell adhesion and extracellular matrix genes.

This project will use zebrafish models to examine the interaction of cohesin mutant leukemic cells with the niche and screen for drugs that would prevent colonization of leukemic stem within the microenvironment. The student will use cutting edge techniques like zebrafish marrow transplantation assays and next-generation sequencing for this project.

Useful information

• Graduate research at the University of Otago
• Scholarships at the University of Otago