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NOBEL PRIZE 2026

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NIHNATIONAL CANCER INSTITUTER01

A stalled chromatin regulatory network that mediates the oncogenic activity of Meningioma-1

Active
Institution
CHILDREN'S HOSP OF PHILADELPHIA, PA
Principal investigator
Kathrin M Bernt
Funding
$438K
Duration
2022–2027
Open portfolio

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Still being scored

Abstract

PROJECT SUMMARY High expression of the transcriptional co-activator Meningioma-1 (MN1) is common in AML, and associated with a poor prognosis. Forced expression of MN1 in murine hematopoietic progenitors induces an aggressive leukemia. We recently discovered that the primary interaction partner of MN1 is the BAF nucleosome- positioning complex. MN1 stabilizes BAF on chromatin. MN1 binding is associated with sustained active enhancer chromatin at enhancers regulating a hematopoietic stem/progenitor program. We hypothesize that MN1 stabilizes promoter-enhancer contacts at these sites through a BAF dependent mechanism. The goal of this project is to uncover the molecular mechanism of MN1-mediated leukemic transformation. A better understanding of how MN1 causes leukemia may identify opportunities for targeted therapies in a patient population who is failing conventional AML therapy.

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R01NATIONAL CANCER INSTITUTECancer Genetics Study Section[CG]leukemiachromatinunderstanding causesamlstabilizesproject uncoverbafhematopoietic

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