We’re thrilled to share the first publication of 2025 from BCASC, published in the Journal of Cell Science in collaboration with the Booth lab.
Every year around 3000 people in the UK develop Acute Myeloid Leukaemia (AML), a cancer of the myeloid line of blood cells. Over 1000 of these cases will be the result of a mutation in the Nucleophosmin (NPM1) gene, the most common genetic alteration in AML. Normal or wild-type NPM1 protein exerts numerous essential physiological roles in the nucleus (the cells control centre which contains the genetic material) and more specifically a sub-compartment of the nucleus, the nucleolus. The nucleolus is responsible for producing and assembling ribosomes which are essential for protein synthesis. We used high resolution imaging to demonstrate that NPM1 is critical for maintaining normal nucleoli architecture and demonstrate that cells with NPM1 mutations have aberrant nucleoli morphology. We show that the aberrant nucleoli phenotype is associated with differences in nucleolar function and chromatin (a mixture of DNA and proteins that forms chromosomes) organisation. Finally, we report the novel finding that NPM1 mutated protein forms distinct aggregates and characterise these for the first time. This work reveals how nucleolar organisation contributes to the molecular mechanisms underpinning NPM1 driven AML revealing novel therapeutic vulnerabilities.
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