# IDP mediated transcriptional stabilization as a cause of AML

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2022 · $289,950

## 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.

## Key facts

- **NIH application ID:** 10419497
- **Project number:** 1R01CA269788-01
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** KATHRIN M BERNT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $289,950
- **Award type:** 1
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10419497

## Citation

> US National Institutes of Health, RePORTER application 10419497, IDP mediated transcriptional stabilization as a cause of AML (1R01CA269788-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10419497. Licensed CC0.

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