Findings published today in the journal Blood show that healthy bone marrow cells were prematurely aged by cancer cells around them. It is well known that aging promotes cancer development. But this is the first time that the reverse has been shown to be true. Importantly, the aged bone marrow cells accelerated the growth and development of the leukemia—creating a vicious cycle that fuels the disease.

The research was led by Dr. Stuart Rushworth from the University of East Anglia (UEA)’s Norwich Medical School, in collaboration with the Earlham Institute and the Norfolk and Norwich University Hospital (UK) and the Buck Institute for Research on Aging in California (US). It was funded by the Rosetrees Trust and Norfolk’s Big C Charity.

The study also identified the mechanism by which this process of premature aging occurs in the bone marrow of leukemia patients and highlights the potential impact this could have on future treatments.

Dr. Rushworth said, “Our results provide evidence that cancer causes aging. We have clearly shown that the cancer cell itself drives the aging process in the neighboring non-cancer cells. Our research reveals that leukemia uses this biological phenomenon to its advantage to accelerate the disease.”

NOX2, an enzyme usually involved in the body’s response to infection, was shown to be present in acute myeloid leukemia (AML) cells—and this was found to be responsible for creating the aging conditions. The research team established that the NOX2 enzyme generates superoxide, which drives the aging process. By inhibiting NOX2, researchers showed the reduction in aged, neighboring, non-malignant cells resulted in slower cancer growth.

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

"Acute myeloid leukemia induces pro-tumoral p16INK4a driven senescence in the bone marrow microenvironment" is published on the cover of Blood (the official journal of the American Society of Hematology) on January 31, 2019.