Mutation in stem cells causes chronic blood disorder

Paroxysmal nocturnal haemoglobinuria (PNH) is a life-threatening disease in which red blood cells are destroyed by the body, causing haemoglobin to appear in the urine, giving it a red hue.

In people living with the chronic condition, the haematopoietic stem cells (HSCs), which give rise to all other blood cells including the natural killer (NK) cells, harbour a mutation in the X-linked PIGA gene. This mutation disrupts the synthesis of the glycosylphosphatidylinositol (GPI) anchor which secures a number of proteins to the cell surface, causing the formation of considerable numbers of NK cells lacking GPI-linked proteins.

A team of researchers led by Graham Cook from the University of Leeds, UK and including Yasser M. El-Sherbiny from Mansoura University in Egypt, studied NK subsets in peripheral blood samples of 47 PNH patients, publishing their findings in Blood.

By staining the cells with antibodies and using fluorescent aerolysin, the researchers found the GPI-negative CD56^bright NK cells to be significantly more abundant in peripheral blood than GPI-positive CD56bright NK cells. This, as well as other findings including impaired response of the GPI-negative cells to chemokines during migration assays, suggests defective cellular trafficking in GPI-negative CD56^bright NK cells, which fail to travel to a niche that GPI-positive CD56bright NK cells can reach, leaving the cells more numerous in peripheral blood.

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