Image courtesy of Dr Kevin Rouault-Pierre's lab
Anthony Nolan’s Cell & Gene Therapy (CGT) team are proud to announce the release of new research from Queen Mary University, using cord blood material provided by Anthony Nolan donors. The research team, led by Dr Syed Mian and Dr Celine Philippe in the lab of Dr Kevin Rouault-Pierre, have helped us better understand a type of cancer called myelodysplastic syndrome (MDS), which can often progress to a more severe kind of blood cancer called acute myeloid leukaemia (AML).
Using cord blood units provided by CGT, the team at Queen Mary University have discovered new ways to help mutated blood stem cells in a particular type of MDS start to make healthy blood cells again.
They found that vitamin B5, a safe drug to give to humans, could encourage the healthy development of red blood cells. This opens up exciting new possibilities in the treatment of MDS, and could potentially help patients live longer and healthier lives before requiring blood transfusions or stem cell transplants.
Myelodysplastic Syndrome (MDS)
In MDS, mutations in your blood stem cells mean that they can no longer make healthy blood cells. Different kinds of MDS cause different kinds of faults in your blood. In this study, the researchers were interested in a particular type of MDS that affects your red blood cells, called MDS with ring sideroblasts (MDS-RS).
Patients with this kind of MDS usually have low levels of haemoglobin, a protein that helps your red blood cells carry oxygen. This is known as anaemia, and can have a range of painful symptoms. MDS-RS can sometimes develop into AML, a more severe blood cancer that can require a stem cell transplant to treat.
Initially, treatments for MDS-RS include drugs that stimulate the growth of red blood cells, but patients can often become resistant to these drugs. Eventually, patients may need frequent blood transfusions, which can increase the risk of developing AML.
In this study, researchers were trying to understand how MDS-RS develops, so that they could come up with new treatment options.
Mutations in MDS-RS
Comparing stem cells from patients with MDS-RS with stem cells from healthy umbilical cord, the researchers studied a common genetic mutation in the MDS-RS stem cells. This mutation, in the gene SF3B1, was causing an error in the ‘citric acid cycle’, which is a crucial molecular pathway that helps our cells make energy from food.
The researchers discovered that this error in the mutated stem cells was causing them to grow underdeveloped red blood cells. Using cord blood cells from Anthony Nolan donors, the team could prove that this mutation was slowing down haemoglobin production in developing red blood cells, and could be the main cause of symptoms in MDS-RS patients with the SF3B1 mutation.
Now that the scientists knew what was slowing down the growth of red blood cells in this kind of MDS-RS, they could attempt to boost the cells by giving them additional ingredients in energy production and haemoglobin manufacture. Think of this like being on a sailboat where one of the sails is torn… if you raise your other sails a little higher, you might be able to compensate for the tear and go faster again!
Treating MDS-RS with Vitamin B5
Vitamin B5 is used by all animals as part of the citric acid cycle, which helps cells extract energy from food and create haemoglobin. Because the researchers knew that the citric acid cycle was damaged in MDS-RS cells with the SF3B1 mutation, they decided to try and grow the cells in vitamin B5 and see if they could restore energy production.
Thankfully, it appeared that vitamin B5 was giving the MDS-RS stem cells more energy and haemoglobin, helping them grow into fully developed red blood cells a bit more effectively! While the researchers don’t think that vitamin B5 could be a full treatment of MDS-RS in itself, they suggest that it could be a supplement to other treatments. There would also have to be more research into the best ways of getting vitamin B5 into the mutated stem cells.
However, we know that vitamin B5 is a safe drug in humans, and it could potentially help reduce the symptoms of MDS-RS and give patients more time before needing more intensive treatments like repeated blood transfusions.
Anthony Nolan's Cord Blood Donors: Providing Hope for New Treatments
Cord blood contains a high concentration of blood stem cells with many different applications in cell and gene science, and contributes to life-saving research every day. The umbilical cord blood provided by Anthony Nolan’s generous cord donors was fundamental in helping these researchers discover why blood cells fail to grow healthily in MDS-RS.
More discoveries like this one will help give patients with cancer more treatment options beyond a stem cell transplant, and can move us closer to a future where every patient has equal access to the best therapies available.