04 February 2019

Acute myeloid leukaemia (AML) causes some healthy cells in bone marrow to age prematurely - creating a ‘vicious cycle’ of ageing and cancer growth, according to new UK research.

Although it is already known that ageing promotes cancer development, this study led by researchers at the University of East Anglia is claimed as the first time the reverse has been shown to also be true.

Researchers showed in experiments with mice that the aged bone marrow stromal cells accelerated the growth and development of the leukaemia, which then triggered further ageing.

The study, published in the journal Blood, also identified the mechanism by which the premature ageing process occurs in the bone marrow of leukaemia patients.

The study was led by Dr Stuart Rushworth from UEA's Norwich Medical School, working with scientists from Earlham Institute and the Norfolk and Norwich University Hospital, and the Buck Institute for Research on Ageing in California, USA. The research was funded by the Rosetrees Trust and Norfolk's Big C Charity.

Dr Rushworth said: “Our results provide evidence that cancer causes ageing. We have clearly shown that the cancer cell itself drives the ageing process in the neighbouring non-cancer cells.

“Our research reveals that leukaemia uses this biological phenomenon to its advantage to accelerate the disease.”

They found that NOX2, an enzyme usually involved in the body's response to infection, was present in AML cells and was responsible for creating superoxide which drives the ageing of bone marrow stromal cells.

Silencing the NOX2 gene in AML cells caused a reduction in the number of aged non-malignant cells, and in turn resulted in slower cancer growth.

“It was not previously known that leukaemia induces ageing of the local non-cancer environment. We hope that this biological function can be exploited in future, paving the way for new drugs”, added Dr Rushworth. 

Source: Abdul-Aziz, A.M., Sun, Y., Hellmich, C., Marlein, C.R., Mistry, J., Forde, E., Piddock, R.E., Shafat, M.S., Morfakis, A., Mehta, T., Di Palma, F., Macaulay, I., Ingham, C.J., Haestier, A., Collins, A., Campisi, J., Bowles, K.M., Rushworth, S.A. (2018) “Acute myeloid leukemia induces pro-tumoral p16INK4a driven senescence in the bone marrow microenvironment”, Blood, available at doi: 10.1182/blood-2018-04-845420


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