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A new study led by the Mead Group in the MRC Weatherall Institute of Molecular Medicine (Radcliffe Department of Medicine) has demonstrated a previously unknown effect of chronic inflammation on TP53-mutant haematopoietic stem cells.

An illustration of a face forming from a storm cloud and blowing at a tree that is almost completely bent over in a windswept green landscape. © Marzia Munafò
Like a storm sweeping through the forest, inflammation depletes healthy stem cells from the bone marrow. Resilient TP53-mutant cells, like mighty trees, withstand the storm and thrive under inflammatory conditions.

TP53 (tumour protein 53) is the most frequently mutated gene in human cancers. In this study, the authors investigated the link between an aggressive type of leukaemia and TP53 mutations in haematopoietic stem cells.

Haematopoietic stem cells (HSCs) can differentiate to produce all blood cell types, which is essential for maintaining a healthy blood system. TP53 mutations in HSCs have previously been associated with a cancer progression pathway that leads to the development of acute myeloid leukaemia. Up until now, the mechanisms by which these TP53-mutated blood stem cells expand and give rise to cancer have remained in the dark.

Under normal circumstances, HSCs will differentiate into white blood cells when the body senses inflammation and the white blood cells produced will help to fight the infection. However, this study showed that, in patients with TP53 mutations in their HSCs, inflammation gave rise to selective expansion of TP53-mutant cells, which cannot differentiate normally.

Read the full story on the MRC Weatherall Institute of Molecular Medicine website