What Causes Chronic Myelomonocytic Leukemia (CMML)?

In a small portion of people, chronic myelomonocytic leukemia (CMML) is linked to a known risk factor, such as prior treatment with chemotherapy. But in most people, the cause of CMML is unknown.

Even though we still don’t know what causes CMML in most cases, researchers have made a lot of progress. They’ve begun to understand how certain changes in the DNA in bone marrow cells may cause CMML to develop.

Here is what we know so far about these gene changes and how they might cause CMML.

CMML and gene changes (mutations)

Cancer is caused by changes in the DNA inside our cells. This is true of all cancers, including CMML.

DNA is the chemical in our cells that makes up our genes. Our genes control how our cells work. Our DNA, which comes from both our parents, affects more than just how we look.

Gene mutations and cancer

Some genes help control when our cells grow, divide to make new cells, or repair mistakes in DNA. Other genes cause cells to die when they’re supposed to. If these genes aren’t working correctly, it can cause cells to grow out of control.

For example:

• Oncogenes: Changes in genes that normally help cells grow, divide, or stay alive can lead to these genes being more active than they should be. At this point, they become oncogenes. Oncogenes can result in cells growing out of control.
• Tumor suppressor genes: 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.
• DNA repair genes: 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 cause cells to grow out of control, which could lead to cancer. To learn more, see Oncogenes, Tumor Suppressor Genes, and DNA Repair Genes.

Gene mutations that cause CMML

Usually, mutations in several different genes inside bone marrow cells are needed before a person develops CMML.

Some of the changes most often seen in CMML cells include mutations in the NRAS, KRAS, JAK2, SETBP1, TET2, ASXL1, RUNX1, and SRSF2 genes. 

Are gene mutations in CMML cells inherited or acquired?

In some types of cancer, gene mutations that increase a person’s risk can be passed down (inherited) from a parent. But inherited gene mutations do not seem to cause CMML. Instead, the gene mutations in CMML cells are acquired during a person’s lifetime.

In a small number of people, the acquired gene mutations in CMML cells might be the result of exposure to cancer-causing chemicals, like chemotherapy. But most often, the gene changes that lead to CMML seem to happen 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 CMML largely affects older people.