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Isoform- and mutation- specific roles of Wilms Tumor 1 in acute myeloid leukemia maintenance (ATAC-Seq)

ABSTRACT: Acute myeloid leukemia (AML) is caused by recurrent mutations in members of the gene regulatory and signalling machinery subverting hematopoietic differentiation. We previously showed that each AML sub-type displays a different gene regulatory network with specific transcription factor families playing distinct roles in maintaining the leukemic phenotype. Here we show that the transcription factor WT1 forms a major node in the gene regulatory networks of multiple AML sub-types. It is frequently mutated and up-regulated in AML and its expression is pedictive for relapse. The WT1 protein exists as different isoforms which we show here to harbor differential chromatin binding and contrasting biological activity, including directing differential splicing. For two main AML subtypes we demonstrate 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 wide-spread role in AML biology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153860 | GEO | 2021/07/30

REPOSITORIES: GEO

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Isoform- and mutation- specific roles of Wilms Tumor 1 in acute myeloid leukemia maintenance (RNA-Seq)

Project description:Acute myeloid leukemia (AML) is caused by recurrent mutations in members of the gene regulatory and signalling machinery subverting hematopoietic differentiation. We previously showed that each AML sub-type displays a different gene regulatory network with specific transcription factor families playing distinct roles in maintaining the leukemic phenotype. Here we show that the transcription factor WT1 forms a major node in the gene regulatory networks of multiple AML sub-types. It is frequently mutated and up-regulated in AML and its expression is pedictive for relapse. The WT1 protein exists as different isoforms which we show here to harbor differential chromatin binding and contrasting biological activity, including directing differential splicing. For two main AML subtypes we demonstrate 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 wide-spread role in AML biology.

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Upregulation of HOXA3 by Isoform-Specific Wilms Tumor 1 Drives Chemotherapy Resistance in Acute Myeloid Leukemia

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Transcription profiling of human Wilms tumor 1 WT1(-KTS) isoform time series induction in U2OS cells

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Global binding of isoforms of Wilms' Tumor gene 1 and H3K4me3 in K562 cells

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Project description:Oligonucleotide expression microarray data used for expression signature associated with WT1 mutations in cytogenetically normal AML patient samples

2011-06-17 | E-TABM-1020 | biostudies-arrayexpress

Oviductal fluid LC-MS/MS - The Wilms tumor protein Wt1 contributes to female fertility by regulating oviductal proteostasis

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2017-04-04 | PXD003283 | Pride

The Wilms' tumour 1 transcription factor regulates epigenetic states via DNA methyltransferase 3A

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