Monash University
Thesis 210401.pdf (50.43 MB)

PU.1 and maturational plasticity in acute myeloid leukaemia

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posted on 2021-04-12, 08:44 authored 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.


Principal supervisor

Ross Dickins

Additional supervisor 1

Matthew McCormack

Year of Award


Department, School or Centre

Central Clinical School

Campus location



Doctor of Philosophy

Degree Type



Faculty of Medicine, Nursing and Health Sciences