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Some cases of myelodysplastic syndrome (MDS) are linked to known risk factors, but most often, the cause is unknown.

Scientists have made great progress in understanding how certain changes in the DNA in bone marrow cells may cause MDS to develop. DNA is the chemical that makes up our genes, which control how our cells function. We usually look like our parents because they are the source of our DNA. But DNA affects more than the way we look.

Some genes control when our cells grow, divide into new cells, and die: 

• Certain genes that help cells grow, divide, and stay alive are called oncogenes. 
• Genes that help keep cell division under control, or cause cells to die at the right time are called tumor suppressor genes. 

Cancers can be caused by gene mutations (defects) that turn on oncogenes or turn off tumor suppressor genes.

Usually mutations in several different genes inside bone marrow cells are needed before a person develops MDS. Some of the mutations most often seen in MDS cells include those in the DNMT3A, TET2, ASXL1, TP53, RUNX1, SRSF2, and SF3B1 genes. Some of these gene changes can be inherited from a parent, but more often they happen during a person’s lifetime.

Inherited gene changes

Researchers have found the gene changes that cause some rare inherited syndromes (like familial platelet disorder with a propensity to myeloid malignancy) linked to an increased risk of developing MDS. This syndrome is caused by inherited changes in the RUNX1 gene. Normally, this gene helps control the development of blood cells. Changes in this gene can lead to blood cells not maturing like they normally would, which can increase the risk of developing MDS.

Gene changes acquired during a person’s lifetime

Often, it’s not known why people without inherited syndromes develop MDS. 

Some outside exposures can lead to MDS by damaging the DNA inside bone marrow cells. For example, tobacco smoke contains chemicals that can damage genes. Exposure to radiation or certain chemicals such as benzene or some chemotherapy drugs can also cause mutations that lead to MDS.

But sometimes the gene changes that lead to MDS seem to occur for no apparent reason. Many of these gene changes are probably just random events that sometimes happen inside a cell, without having an outside cause. 

Gene changes inside cells can build up over a person’s lifetime, which might help explain why MDS largely affects older people.