Scientists have discovered that boosting the number of fat cells in the bone marrow can help attack a dangerous type of blood cancer.
Acute myeloid leukaemia is an aggressive cancer of the blood system. It originates in the bone marrow and affects the myeloid cell which would normally develop into red blood cells and certain types of immune cells. However, this type of leukaemia prevents the myeloid cell from maturing causing a deficit of red blood cells and certain immune cells; leaving the patient anaemic, fatigued and prone to infection.
Publishing in Nature Cell Biology, Mick Bhatia and his colleagues at McMaster University in Canada report work that may lead to a new therapeutic approach to treating the disease. Mick and his team had been looking at samples of bone marrow from patients with leukaemia under a microscope. They made an observation that as the leukaemia developed the number of fat cells in the bone marrow decreased. Mick explained, “We then asked the question, was there a cause and effect relationship between reduced fat and increased leukaemia?”.
The traditional approach to viewing and treating the disease is that the growing cancer needs to be killed. However, this new therapeutic approach explores whether there is something that can be changed in the environment in which the cancer grows, that could kill the leukaemic cells. Mick and his team had the fat cells in the bone marrow firmly in sight.
Their idea was to boost the number of bone marrow fat cells to see if it affected the growth of the leukaemic cells. To do this they used a type of drug called a PPARγ agonist, which is currently used to treat diabetes. They tested this drug in two main ways. First, they tested it on samples of patients' bone marrow in a dish. They also used a second testing model where they transplanted patients' bone marrow cells into mice, recreating a human bone marrow environment in another living organism.
The results were surprising. Not only did this approach boost the number of fat cells and reduce the number and function of the leukaemic cells, it also boosted the number of healthy blood cells. This is important because the current treatment of chemotherapy kills both the leukaemic cells and the healthy blood cells. This can compromise the patient’s immune system, something which can be fatal.
Mick thinks that this treatment may work well in synergy with chemotherapy with minimal side effects. This is because they used a low dose that equated to 20% of what is normally used in the setting of diabetes, which is unusual for a ‘proof-of-concept’ study. In addition, the drug was administered over a much shorter period of time than would be the case in a long-term disease like diabetes and was even administered orally in the mouse model.
There are two main challenges that now face this field of research. First is to get approval to begin clinical trials in humans as soon as possible, which can be a lengthy process. However, since this is a drug that is being repurposed it should, in theory, make it to the bedside of patients quicker than a new drug, which can often take 10+ years to go from bench to bedside. Mick would like to see clinical trials underway in 3 years time.
In addition, there are a myriad of mechanistic questions to answer. The researchers do not know how the fat cells impair the leukaemic cells and boost the healthy blood cells. There might be many different proteins at play here, and uncovering the mechanism “down to the electron spin” as Mick put it, may be more than a lifetime’s work.
There is also the tantalising possibility that boosting the number of fat cells in the bone marrow may be achieved via a non-pharmacological method. Mick mentioned that this research has ignited the imaginations of those who work in nutrition science, several of whom have contacted him. This is one discovery to keep an eye on.
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