Diabetes drugs treat leukaemia

Myeloid leukaemia is an aggressive cancer of the blood system, it prevents myeloid cells from developing into red blood cells and immune cells, leaving patients anaemic, fatigued and prone to infection. This week, scientists at McMaster University in Canada have found an innovative way to attack the cancer cells by boosting the number of fat cells in the bone marrow using a drug that is currently being used for diabetes. Leading the investigation is Mick Bhatia who explained to Michael Wheeler how they found this exciting discovery.

Mick - There were a lot of cell types in the bone marrow environment. The bone marrows environment’s made up of a lot of cells other than blood and there were particular cells types, specifically fat cells called the adipocytes, that were decreasing as the disease started to progress and became higher and higher. In cases where the chemotherapy failed, it looked like those cells were almost completely absent. Once were were convinced of that we then asked the question was there a cause and effect relationship between reduced fat and increased leukemia?

Michael - So their hypothesis was if they could boost the number of fat cells in the bone marrow that might affect the development of leukemia. They tested the idea using samples of patients’ bone marrow in a dish, but they also transplanted patients’ bone marrow cells into mice to recreate a human bone marrow environment in another living organism. The team found they were able to boost the number of fat cells in the bone marrow by administering a drug that is currently being used for diabetes…

Mick - By increasing the fat cells in that bone marrow environment it actually suppressed leukemia cells. What we didn’t count on was that, at the same time as killing the leukemia cells, it turned out we were activating the normal blood cells.

Michael - This is an exciting result as traditional chemotherapy kills both the leukemia cells and the healthy blood cells. The job of those healthy blood cells is to keep the rest of the body healthy, so losing them can be fatal. Selective impairment of just the leukemia cells seems promising... so how exactly were the leukemia cells affected?

Mick - In addition to their numbers, their general function is definitely reduced. We just don’t know mechanistically how this is happening. It wasn’t just about you have 100 cells and you went down to 50, those 50 cells that are remaining, if you waited long enough, were very debilitated, they were very weak 50 cells. They didn’t grow as fast as they normally would have, so I think it’s both the quantity and quality of those leukemic cells.

Michael - This dual effect on both the number and function of the leukemia cells should, in theory, help prevent the cancer from spreading. So were these mice cured of cancer?

Mick - We never let the experiments go to the point where we’re trying to cure the mice, we’re just looking for general effects. We have taken some mice out a little bit longer, meaning we would give them the drug for two weeks, but then we would wait longer. We do have some mice that we didn’t report in the paper that actually had no leukemia at all. Whether that is curing them of leukemia or not, we could only be speculating at this point because it’s going to be a very different scenario in patients which, I think, we’re very anxious to go to that next step.

Michael - So often, promising therapies in animal models fail to make it to the bedside of patients, so what challenges lay ahead for this discovery to make that next step?

Mick - I think the main challenges we’ll probably face will not be much different than other drugs. A drug that’s being repurposed has to be produced by a manufacturer. We have to have some sort of level of sponsorship. Getting the sponsorship, getting the funding, and then getting the organisation of all of the nurses, the physicians, clinical sites to be able to bring in the patients in and do a trial where we’ve got good numbers and we can draw conclusions.