Projects per year
Abstract
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.
Original language | English |
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Article number | 109010 |
Number of pages | 26 |
Journal | Cell Reports |
Volume | 35 |
Issue number | 3 |
DOIs | |
Publication status | Published - 20 Apr 2021 |
Bibliographical note
Publisher Copyright:© 2021 The Author(s)
Keywords
- FLT3-ITD AML
- WT1 binding motif
- WT1 isoforms
- Wilms tumour 1
- acute myeloid leukemia
- chromatin
- early growth response factors
- gene regulatory networks
- oncogenic signaling
- t(8;21) AML
- transcription
ASJC Scopus subject areas
- General Biochemistry,Genetics and Molecular Biology
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Dive into the research topics of 'Isoform-specific and signaling-dependent propagation of acute myeloid leukemia by Wilms tumor 1'. Together they form a unique fingerprint.Projects
- 2 Finished
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Finding therapeutic targets in FLT3-ITD AML using a systems biology approach
Cockerill, P. (Co-Investigator) & Bonifer, C. (Principal Investigator)
1/09/19 → 31/12/23
Project: Research Councils
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Mechanistic insights into aberrant transcriptional programming in acute myeloid leukaemia
Bonifer, C. (Principal Investigator) & Cockerill, P. (Co-Investigator)
1/07/15 → 31/12/21
Project: Research