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NOBEL PRIZE 2026

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NIHNATIONAL CANCER INSTITUTER01

IDP mediated transcriptional stabilization as a cause of AML

Active
Institution
CHILDREN'S HOSP OF PHILADELPHIA, PA
Principal investigator
Kathrin M Bernt
Funding
$236K
Duration
2022–2027
Open portfolio

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Abstract

PROJECT SUMMARY High expression of the intrinsically disordered protein 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. Intriguingly, MN1’s entire coding frame is disordered. We hypothesize that MN1 causes AML by overstabilizing transcriptional hubs by increasing multi- valent, low affinity interactions that result in high local concentrations of BAF and early hematopoietic transcription factors. A better understanding of how MN1 causes leukemia may identify opportunities for targeted therapies in a patient population who is failing conventional AML therapy.

LOADING MOONBASE SCORE

R01NATIONAL CANCER INSTITUTECancer Molecular Pathobiology Study Section[CAMP]leukemiachromatinunderstanding causesidpamldisorderedbafhematopoietic

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