Article highlights & insights
Acute myeloid leukaemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear.
Here, Loke et al compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors.
RUNX1-EVI1 directs a stem cell-like transcriptional network reliant on GATA2, whereas that of RUNX1-ETO-expressing cells is more mature and depends on RUNX1. However, both types of AML are dependent on the continuous expression of the fusion proteins.
This data provides a molecular explanation for the differences in clinical prognosis for these types of AML.
Acute myeloid leukaemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear.
Here, Loke et al compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors.
RUNX1-EVI1 directs a stem cell-like transcriptional network reliant on GATA2, whereas that of RUNX1-ETO-expressing cells is more mature and depends on RUNX1. However, both types of AML are dependent on the continuous expression of the fusion proteins.
This data provides a molecular explanation for the differences in clinical prognosis for these types of AML.
Institute Authors
Groups
Group leader
Research topics & keywords
Our Research
Our research spans the whole spectrum of cancer research from cell biology through to translational and clinical studies
Research Groups
Our research groups study many fundamental questions of cancer biology and treatment
Our Facilities
The Institute has outstanding core facilities that offer cutting edge instruments and tailored services from expert staff
Latest News & Updates
Find out all our latest news