Isoform-specific and signaling-dependent propagation of acute myeloid leukemia by Wilms tumor 1

Isoform-specific and signaling-dependent propagation of acute myeloid leukemia by Wilms tumor 1

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Summary: 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 nutella christmas ornament 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 hermit crab ornaments transcription factor hub that controls AML growth.WT1 therefore plays a central and widespread role in AML biology.