Award
National Cancer Institute 5R01CA269788-05
IDP mediated transcriptional stabilization as a cause of AML
Recipient
CHILDREN'S HOSP OF PHILADELPHIA
Award Amount
$240,090.00
Ceiling
$240,090.00
Awarded
March 25, 2026
Identifier
5R01CA269788-05
This NIH grant supports research on how the intrinsically disordered protein MN1 contributes to acute myelocytic leukemia (AML) by stabilizing transcriptional hubs, aiming to identify novel therapeutic targets for AML patients with poor prognosis.
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 aggressive leukemia. MN1 stabilizes the BAF nucleosome-positioning complex on chromatin, associated with active enhancer chromatin at hematopoietic stem/progenitor gene 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.