Thesis 210401.pdf (50.43 MB)
PU.1 and maturational plasticity in acute myeloid leukaemia
thesisposted 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.