Abnormal nucleoli architecture and aggregate formation in nucleophosmin mutated acute myeloid leukaemia.

ABSTRACT: Mutations in the nucleophosmin (NPM1) gene represent the most common genetic alteration in acute myeloid leukaemia (AML) and result in mis-localisation of the mutated protein from a predominantly nucleolar localisation to a predominantly cytoplasmic distribution. Here, we use high resolution imaging to demonstrate that NPM1 is crucial for maintaining normal nucleoli architecture and specifically the integrity of the enigmatic nucleoli rim, the least understood nucleolar compartment. We demonstrate that cell lines and primary cells with NPM1 mutations from individuals with AML have aberrant nucleoli architecture; intriguingly this abnormal nucleolar phenotype is reversible. Using a surrogate for rRNA synthesis, we show that the aberrant phenotype is associated with differences in nucleolar

SUBMITTER: Grundy M 

PROVIDER: S-EPMC12148033 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature