We will investigate the emergence of drug resistant dysplastic haematopoietic stem cells using patient derived blood stem cells and mouse xenograft models. Bone marrow derived haematopoietic stem cells from patients with myelodysplastic syndrome undergoing treatment on an investigator initiated clinical trial led by Professor Pimanda will be barcoded and transplanted into mice. Engrafted blood stem cells will be harvested before and after drug treatment for single cell genotyping and transcriptomics to identify drug resistant signatures. These data will be combined with proteomic analysis to identify markers of emerging drug resistant cells in primary patient samples and to identify drugs that will be tested in mouse xenograft models.
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Women's and Children's Health
Prince of Wales Clinical School