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

A lot of progress has been made in understanding how certain changes in the DNA in bone marrow cells may cause MDS to develop.

Changes (mutations) in genes

Cancer is caused by changes in the DNA inside our cells. DNA is the chemical in our cells that makes up our genes, which control how our cells function. Our DNA, which comes from both our parents, affects more than just how we look.

Some genes normally help control when our cells grow, divide to make new cells, or repair mistakes in DNA, or they cause cells to die when they’re supposed to. If these genes aren’t working properly, it can lead to cells growing out of control. For example:

• Changes in genes that normally help cells grow, divide, or stay alive can lead to these genes being more active than they should be, causing them to become oncogenes. These genes can result in cells growing out of control.
• Genes that normally help keep cell division under control or cause cells to die at the right time are known as tumor suppressor genes. Changes that turn off these genes can result in cells growing out of control.
• Some genes normally help repair mistakes in a cell’s DNA. Changes that turn off these DNA repair genes can result in the buildup of DNA changes within a cell, which might lead to them growing out of control.

Any of these types of DNA changes might lead to cells growing out of control, which might lead to cancer. To learn more, see Oncogenes, Tumor Suppressor Genes, and DNA Repair 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 are acquired during a person’s lifetime.

Inherited gene changes

Researchers have found the gene changes that cause some rare inherited syndromes that are linked to an increased risk of developing MDS.

For example, in a condition called RUNX1 familial platelet disorder with associated myeloid malignancies, the cells have an inherited change 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 a person’s risk of 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 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.