Journal
CELL REPORTS
Volume 35, Issue 3, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.109010
Keywords
-
Categories
Funding
- Medical Research Council
- Leukaemia UK Clinical Research Training Fellowship
- Blood Cancer UK [15001]
- Medical Research Council [MR/S021469/1]
Ask authors/readers for more resources
WT1 is a key transcription factor in AML, frequently mutated or upregulated in multiple AML subtypes and predictive for relapse. Different isoforms of WT1 exhibit contrasting biological activities, including enhanced proliferation in two main AML subtypes. WT1 is responsive to oncogenic signaling and part of a transcription factor hub controlling AML growth.
Acute myeloid leukemia (AML) is caused by recurrent mutations in members of the gene regulatory and signaling machinery that control hematopoietic progenitor cell growth and differentiation. Here, we show that the transcription factor WT1 forms a major node in the rewired mutation-specific gene regulatory networks of multiple AML subtypes. WT1 is frequently either mutated or upregulated in AML, and its expression is predictive for relapse. The WT1 protein exists as multiple isoforms. For two main AML subtypes, we demonstrate that these isoforms exhibit differential patterns of binding and support contrasting biological activities, including enhanced proliferation. We also show that WT1 responds to oncogenic signaling and is part of a signaling-responsive transcription factor hub that controls AML growth. WT1 therefore plays a central and widespread role in AML biology.Y
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available