Nuclear Phase Separation Drives NPM1-mutant Acute Myeloid Leukemia.

ABSTRACT: During cancer development, mutations promote gene expression changes that cause transformation. Leukemia is frequently associated with aberrant HOXA expression driven by translocations in nucleoporin genes or KMT2A, and mutations in NPM1. How disparate mutations converge on this regulatory pathway is not understood. Here we demonstrate that mutant NPM1 (NPM1c) forms nuclear condensates in multiple human cell lines, mouse models, and primary patient samples. We show NPM1c phase separation is necessary and sufficient to coordinate the recruitment of NUP98 and KMT2A to condensates. Through extensive mutagenesis and pharmacological destabilization of phase separation, we find that NPM1c condensates are necessary for regulating gene expression, promoting in vivo expa

SUBMITTER: Datar GK 

PROVIDER: S-EPMC12154763 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature