Award
National Cancer Institute 5R01CA269788-05
IDP mediated transcriptional stabilization as a cause of AML
Recipient
Children's Hospital of Philadelphia, Philadelphia, PA, United States
Award Amount
$240,090.00
Ceiling
$240,090.00
Awarded
March 25, 2026
Identifier
5R01CA269788-05
This NIH grant funds research on the role of the intrinsically disordered protein MN1 in acute myelocytic leukemia (AML), focusing on how MN1 stabilizes transcriptional hubs to promote leukemia and exploring potential targeted therapies.
Description
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. MN1 stabilizes BAF on chromatin, associated with active enhancer chromatin at hematopoietic stem/progenitor gene regulatory regions. MN1’s entire coding frame is disordered, hypothesized to cause AML by overstabilizing transcriptional hubs through multivalent, low affinity interactions, increasing local concentrations of BAF and early hematopoietic transcription factors. Understanding MN1’s role may lead to targeted therapies.