Myelodysplastic Syndrome Causes and Risk Factors

Myelodysplastic syndrome (MDS) occurs when the blood-forming cells in the bone marrow do not produce enough healthy blood cells. Instead, they create abnormal cells that fail to develop and function poorly. In time, symptoms may appear, such as easy bleeding and bruising, fatigue, frequent infections, pallor, shortness of breath and pinpoint-sized red spots just beneath the skin (petechiae). In some cases, MDS may progress to acute myeloid leukemia (AML), a more aggressive blood cancer.

In the United States, approximately 4.5 people per 100,000 are diagnosed with myelodysplastic syndrome each year. Treatment can vary based on the patient’s age, overall health and personal preferences. Some individuals may undergo high-dose chemotherapy followed by bone marrow transplantation (BMT).

What causes myelodysplastic syndrome?

MDS originates in the hematopoietic stem cells in the bone marrow, which are responsible for producing all types of healthy blood cells. Based on the body’s needs, these cells can develop into red blood cells that carry oxygen, white blood cells that fight infection or platelets that support blood clotting.

If a genetic mutation occurs in a single hematopoietic stem cell, it can interfere with normal blood cell production. As a result, the bone marrow may produce abnormal cells that do not fully mature. Instead, the dysfunctional cells may die prematurely or accumulate in the bone marrow, crowding out healthy blood cells.

The precise cause of the genetic mutation that leads to myelodysplastic syndrome is not fully understood. Primary (de novo) myelodysplastic syndrome—which accounts for up to 90% of MDS diagnoses—develops without an identifiable trigger. Secondary myelodysplastic syndrome is associated with cellular DNA damage that may occur during cancer treatment, such as chemotherapy or radiation therapy.

What are the risk factors for myelodysplastic syndrome?

MDS is a complex condition that has been linked to several characteristics, behaviors and exposures. While some of these risk factors can be modified or influenced to a certain extent, others cannot.

Myelodysplastic syndrome risk factors that can be controlled

Modifiable risk factors for MDS include:

• Exposure to chemicals – Prolonged contact with certain harmful substances, including benzene, pesticides, nitro-organic explosives, diesel derivatives, solvents and chemical fertilizers, has been traced to MDS.
• Exposure to ionizing radiation – High doses of radiation used in prior cancer treatment may increase the likelihood of developing myelodysplastic syndrome in the future.
• Tobacco use – Smoking is a known risk factor for many types of cancer and other potentially serious health issues, including MDS.

Myelodysplastic syndrome risk factors that cannot be managed

Several risk factors for MDS cannot be changed. These include:

• Advanced age – The likelihood of developing myelodysplastic syndrome increases over time, especially after age 70.
• Cancer treatment – Certain types of high-dose chemotherapy and radiation therapy can cause long-term damage to bone marrow cells, raising the risk of MDS.
• Family history – Certain inherited cancer predisposition syndromes, such as Fanconi anemia, Diamond-Blackfan anemia, familial platelet disorder, severe congenital neutropenia or Shwachman-Diamond syndrome, can increase the risk of myelodysplastic syndrome.
• Genetic mutations – Clonal hematopoiesis (CH) mutations, which are age-related genetic changes in blood-forming cells, have been linked to MDS.

Can myelodysplastic syndrome be prevented?

Complete prevention of MDS is not currently possible due to the complexity of its causes. However, certain steps can be taken to help reduce risk. These include:

• Avoiding tobacco use – Quitting smoking can lower the risk of myelodysplastic syndrome as well as many other serious health issues.
• Avoiding unnecessary medical treatments – Limiting exposure to high-dose chemotherapy and radiation therapy (unless clinically necessary) can help prevent cellular damage.
• Having regular medical checkups – Early detection of blood disorders, CH mutations and other risk factors can allow for prompt intervention when needed.
• Limiting exposure to known carcinogens – Adhering to workplace safety guidelines can help reduce contact with toxic chemicals and other harmful substances.
• Promoting good health – Eating a balanced diet, getting regular exercise and managing stress can support immune function and general wellness.

Clonal hematopoiesis mutations and the CARDIO-CATCH Clinic at Moffitt Cancer Center

Through extensive research, the scientists and clinicians at Moffitt have confirmed that CH mutations can significantly elevate the risk of MDS, AML and cardiovascular disease. These genetic mutations are found in up to 20% of adults 70 and older, with even higher rates in cancer patients.

In recognition of the importance of early detection and proactive care, Moffitt has established the Cardiology Counseling and Therapeutics for Clonal Hematopoiesis (CARDIO-CATCH) Clinic. Through this unique and important program, we provide comprehensive evaluation and management services for individuals with CH mutations, whether or not they have a current cancer diagnosis.

The goals of Moffitt’s CARDIO-CATCH Clinic are to:

• Identify individuals with CH mutations
• Monitor and reduce the risk of MDS, AML and cardiovascular events, such as heart failure, heart attack and stroke
• Foster collaboration among specialists in hematology, cardiology, molecular diagnostics and genetics
• Develop targeted therapeutic strategies through clinical trials

As one of the first programs of its kind in the United States, Moffitt’s CARDIO-CATCH Clinic integrates cancer risk assessment with cardiovascular health management. The program’s pilot phase aims to screen 500 patients with solid tumors—particularly breast and gastrointestinal cancers—for CH mutations. In the long term, our researchers plan to expand mutational screening to thousands of archived blood samples, helping to clarify how specific genetic changes can influence cancer and heart disease risk. By closely following individuals with CH mutations, we can intervene earlier, improving both cancer-related and cardiovascular outcomes.

Moffitt’s innovative CARDIO-CATCH Clinic stands as a testament to our commitment to advancing precision medicine and specialized cancer care, ushering in a new era in the management of hematological cancer precursor conditions.

Benefit from world-class care at Moffitt Cancer Center

Moffitt’s Malignant Hematology Program is one of the largest MDS programs in the world, offering our patients access to advanced diagnostics, leading-edge treatments and a robust portfolio of clinical trials. Our experts are deeply engaged in studying both inherited and acquired risk factors for myelodysplastic syndrome, with the overarching goal of improving its prevention, early detection and treatment.

If you would like to learn more about myelodysplastic syndrome causes and risk factors, you can request an appointment with a specialist in our Malignant Hematology Program by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.