Isoform-specific and signaling-dependent propagation of acute myeloid leukemia by Wilms tumor 1
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
- Chiba University Graduate School of Medicine
- AGE Research Group, NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle upon Tyne Hospitals Trust, Newcastle, UK.
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.
|Number of pages||26|
|Publication status||Published - 20 Apr 2021|
- 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