Stopping blood cancer before it starts
To mark World Cancer Day (Sunday 4 February 2018), here's a look at the research of two of our scientists who are working on ways to prevent a benign condition called monoclonal gammopathy of undetermined significance (MGUS) from developing into myeloma
Myeloma is a type of blood cancer that affects the plasma cells, which are responsible for producing antibodies (proteins that help our bodies fight off infections). Plasma cells come in different types that are specialised to make one of five different antibodies. Because the antibodies have different functions, the immune system normally keeps tight control over how much of each antibody is produced.
In myeloma, a genetic fault means that one particular plasma cell starts multiplying out of control, which crowds out the healthy cells in the bone marrow. The mutated plasma cell also creates an abnormal antibody called a paraprotein. Paraproteins are unable to fulfil their role in the immune system because they do not work properly, so one of the signs of myeloma is getting frequent infections. Myeloma has several other effects on the body, including the breakdown of bone tissue, anaemia (low red blood cell count), and kidney failure.
Currently, it is possible to treat myeloma, but not to cure it, and over half of the 4,200 people diagnosed with myeloma each year will not survive longer than five years. It’s therefore very important to find new ways to prevent or treat myeloma. One way to do this is through investigating a non-cancerous condition called monoclonal gammopathy of undetermined significance (or monoclonal gammopathy of unknown significance, both shortened to MGUS), which often precedes myeloma and is diagnosed in about 4,600 people each year.
MGUS is similar to myeloma in that there is a spike in the number of one type of antibody, though not such a large spike as in myeloma.
However, people with MGUS normally do not have any symptoms and may only discover they have it during a blood test for some other condition. Not everyone with MGUS will develop myeloma, but around 1-2% of people with MGUS will do so each year, and we still don’t know how this happens. Two of our researchers, Dr Surinder Sahota and Professor Claire Edwards, are investigating mechanisms that could drive the transformation of MGUS to myeloma, with the hope of developing ways to prevent the transformation from happening.
Sequencing DNA to find out what genetic changes happen between MGUS and myeloma could help Dr Sahota develop personalised treatments. Image credit: MIKI Yoshihito from Sapporo City, Hokkaido, JAPAN, DNA sequence, CC BY 2.0
The progression of MGUS is different in different people, because multiple genetic changes lead to MGUS. Even within one person, different groups of myeloma cells may have different genetic faults because each time a myeloma cell divides, the new cells can pick up further genetic changes. This genetic diversity can make myeloma very difficult to treat because not all myeloma cells respond in the same way to the same treatment.
At the University of Southampton, Dr Surinder Sahota and his team are using a technique called DNA sequencing to investigate the genetic changes that happened in the cells of people who had MGUS that progressed to myeloma. By comparing the genetic profile of MGUS cells with those of myeloma cells, they hope to gain a deeper understanding of the changes that happen as MGUS progresses, and how those changes might differ between different people. Eventually, Dr Sahota believes, this should help create more personalised and more effective treatments for myeloma.
Since not everyone with MGUS goes on to develop myeloma, there must be factors that can affect the likelihood of disease progression. Professor Claire Edwards at the University of Oxford investigates several possible factors in her Bloodwise-funded studies, including adiponectin, a hormone that is known to be decreased in people with myeloma compared to other people.
Professor Claire Edwards
In April, Professor Edwards and her team will begin a new project looking at bone morphogenetic proteins (BMPs), a family of proteins which can influence the growth and health of cells and are known to be involved in other kinds of cancer. In her past research, Professor Edwards found that inhibiting BMPs with drugs reduced the levels of bone damage and anaemia in myeloma; she believes that these drugs might also cause myeloma cells to stop growing. The team will now investigate whether inhibiting BMPs can help treat MGUS and myeloma, and whether this technique can be effectively used in combination with chemotherapy, potentially opening up a new treatment option for these diseases.
We hope that one day it will be possible to prevent some blood cancers from happening in the first place. Thank you to all our supporters for helping researchers like Dr Sahota and Professor Edwards get closer to this goal.
Read our new fact sheet about MGUS.