MDS, or myelodysplastic syndromes, is a group of blood cancers in which the bone marrow fails to produce enough healthy blood cells. Instead of maturing into functional red blood cells, white blood cells, or platelets, the cells develop abnormally and often die before they ever leave the bone marrow. The result is a shortage of one or more types of blood cells, leading to symptoms like persistent fatigue, frequent infections, and unusual bruising or bleeding. MDS is most commonly diagnosed in people in their 70s and is uncommon before age 50.
How MDS Develops in the Bone Marrow
Bone marrow is the spongy tissue inside your bones that acts as a factory for blood cells. In a healthy person, stem cells in the marrow divide and mature into red blood cells (which carry oxygen), white blood cells (which fight infection), and platelets (which help blood clot). In MDS, a genetic mutation arises in one of those stem cells, creating a defective clone that begins to crowd out normal, healthy cells.
The defective cells look abnormal under a microscope and don’t mature properly. In early-stage MDS, the main problem is that these faulty cells undergo programmed cell death at unusually high rates, so they never make it into the bloodstream in useful numbers. As the disease progresses, additional mutations can accumulate. In some cases, the abnormal cells stop dying and start multiplying uncontrollably, which is how MDS can transform into acute myeloid leukemia (AML).
Symptoms of MDS
The symptoms of MDS depend on which blood cell types are most affected. Anemia, a shortage of red blood cells, is the most common problem. It causes fatigue, weakness, dizziness, shortness of breath, and difficulty exercising. Fatigue in MDS is nearly universal and often feels worse than the degree of anemia alone would explain.
A shortage of white blood cells (called neutropenia) makes you more vulnerable to infections. You might notice recurring fevers, gum inflammation, or infections that take longer to clear. A low platelet count (thrombocytopenia) shows up as easy bruising, tiny red spots on the skin called petechiae, or unusual bleeding from the gums or nose. Some people have low counts in all three cell types at once.
Because these symptoms overlap with many other conditions, MDS is often discovered during routine blood work before a person notices anything wrong.
Who Gets MDS
Roughly 10,000 or more people are diagnosed with MDS in the United States each year, though some estimates run significantly higher because the condition can be underreported. The risk rises sharply with age. Prior exposure to certain chemotherapy drugs or radiation therapy for a previous cancer is one of the strongest known risk factors. Long-term exposure to industrial chemicals like benzene also increases risk. In many cases, no clear cause is identified.
How MDS Is Diagnosed
Diagnosis begins with a standard blood test that reveals low counts in one or more cell types. A blood smear, where a drop of blood is examined under a microscope, can show abnormally shaped cells that hint at MDS. But the definitive test is a bone marrow biopsy. A small sample of marrow is drawn from the hip bone and examined for two things: the percentage of immature cells called blasts and signs of abnormal cell development (dysplasia).
In healthy marrow, blasts make up less than 5% of cells. Higher blast percentages indicate more advanced disease. Once blasts reach 20% or more, the diagnosis shifts from MDS to acute myeloid leukemia.
Genetic testing of the marrow sample is a critical part of the workup. Chromosomal abnormalities are found in roughly half to two-thirds of MDS patients using standard methods, and newer techniques detect them in an even higher percentage. These genetic findings help determine the subtype of MDS and play a major role in predicting how the disease will behave.
MDS Subtypes and Classification
MDS is not a single disease. It’s classified into subtypes based on which cell lines are abnormal, how many blasts are in the marrow, and which genetic mutations are present. Two major classification systems exist (from the World Health Organization and the International Consensus Classification), and they differ in some details, but both recognize certain key subtypes.
One important subtype involves a mutation in a gene called TP53. When both copies of this gene are knocked out, the disease tends to behave more aggressively. Another subtype is defined by a mutation in a gene called SF3B1, which is generally associated with a better outlook. A subtype linked to a specific chromosomal deletion, del(5q), responds well to a particular targeted therapy. Knowing the exact subtype shapes every treatment decision that follows.
Risk Scoring and Prognosis
Doctors use scoring systems to estimate how MDS will progress for each individual patient. The most widely used is called the IPSS-R (Revised International Prognostic Scoring System), which assigns a risk category based on blood counts, blast percentage, and chromosomal abnormalities. A newer version, the IPSS-M, incorporates mutations across 31 genes and provides an even more precise picture.
Outcomes vary enormously by risk category. Patients in the very low risk group have a median survival of nearly 9 years, meaning half live longer than that. Those in higher risk categories face significantly shorter timelines. The scoring system also predicts the likelihood of transformation to leukemia, which is the most serious complication of MDS.
Progression to Leukemia
Historically, 30 to 40% of all MDS patients eventually progress to acute myeloid leukemia. For patients initially classified as lower risk, about 15% progress to AML, some passing through a higher-risk MDS stage first and others converting directly. The median time from a lower-risk diagnosis to AML transformation is roughly 29 months in those who do progress. Higher-risk patients face a faster and more likely transition.
Treatment Options
Treatment depends heavily on the risk category. For lower-risk MDS where anemia is the main problem, the first approach is often medications that stimulate the bone marrow to produce more red blood cells. If those don’t work, the specific genetic profile guides the next step. Patients with the del(5q) chromosomal deletion typically respond to lenalidomide. Those with SF3B1 mutations or ring sideroblasts (a type of abnormal red blood cell precursor) may benefit from luspatercept, a drug that helps red blood cells mature more effectively.
For higher-risk MDS or when multiple cell types are affected, treatment often involves drugs called hypomethylating agents, such as azacitidine or decitabine. These work by reactivating genes that the cancer has silenced, slowing the disease’s progression. Many patients receive regular transfusions of red blood cells or platelets to manage symptoms while these treatments take effect.
The only treatment with the potential to cure MDS is an allogeneic stem cell transplant, in which a donor’s healthy stem cells replace the patient’s defective bone marrow. This is an intensive procedure historically reserved for younger, fitter patients. However, a study from Dana-Farber Cancer Institute found that transplant also benefits older adults (ages 50 to 75) with intermediate or high-risk MDS. Nearly 50% of patients who received a transplant from a matched donor were alive at follow-up, compared to about 26% of those treated with other therapies alone. The catch is that transplant carries serious risks, including graft failure and life-threatening complications, so it’s not appropriate for everyone.