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Fighting leukaemia colonisation of the haematopoietic niche

Year:
2023
Duration:
36 months
Approved budget:
$1,198,340.00
Researchers:
Professor Julia Horsfield
,
Dr Jisha Antony
,
Professor Dr Stefan Bohlander
,
Dr Andy Wood
,
Dr Robyn Lints
,
Mr Gregory Gimenez
Host:
University of Otago
Health issue:
Blood disorders/haematology
Proposal type:
Project
Lay summary
Acute myeloid leukaemia (AML) has a low survival rate of 22% in NZ. Treatment options for AML are limited and new strategies are needed to combat this disease. Understanding the function of AML-associated gene mutations is required to develop new therapies. Mutations in genes of the cohesin complex are present in ~12-20% of AML. Leukaemia stem cells can survive and evade treatment through interaction with the surrounding microenvironment known as the ‘niche’. We found that cohesin mutation enhances adhesive characteristics of leukaemia cells. We propose that these characteristics could promote increased interaction and colonisation of the leukemic cells into the niche. Zebrafish are an excellent model to study leukaemia development in vivo. This project will utilise cohesin mutant zebrafish models to examine the interaction and invasion potential of cohesin mutant cells within the niche, and determine whether niche interactions can be targeted for therapeutics.