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PU.1 and maturational plasticity in acute myeloid leukaemia

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thesis
posted on 12.04.2021, 08:44 by ETHAN PAUL OXLEY
Acute myeloid leukaemia (AML) is a haematological malignancy often framed in the context of a hierarchical leukaemia stem cell model whereby only a small proportion of immature leukaemia cells maintain the entire tumour bulk. In this project, we demonstrate that mature and non-leukaemogenic AML cells can reacquire leukaemia-initiating activity and promote disease progression through de-differentiation. Furthermore, extensive mechanistic and transcriptomic analysis revealed that this maturational plasticity was largely dependent on the myeloid transcription factor PU.1, a protein frequently disrupted in AML. These results prompt new interpretations of intratumoural phenotypic heterogeneity in AML, and may reveal novel avenues of disease relapse.

History

Principal supervisor

Ross Dickins

Additional supervisor 1

Matthew McCormack

Year of Award

2021

Department, School or Centre

Central Clinical School

Campus location

Australia

Course

Doctor of Philosophy

Degree Type

DOCTORATE

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