MDS, or myelodysplastic syndromes, is a group of blood cancers in which the bone marrow fails to produce enough healthy blood cells. Instead of releasing normal red blood cells, white blood cells, and platelets into the bloodstream, the marrow churns out defective, immature cells that don’t work properly. The result is a shortage of one or more blood cell types, which leads to fatigue, infections, and bleeding problems. MDS is most commonly diagnosed in people in their 70s and is uncommon before age 50.
What Happens in the Bone Marrow
Normally, stem cells in the bone marrow mature into red blood cells (which carry oxygen), white blood cells (which fight infection), and platelets (which stop bleeding). In MDS, a genetic change occurs in one of those stem cells, creating an abnormal clone that outcompetes healthy cells. This clone produces blood cells that look and behave abnormally, a process doctors call “ineffective hematopoiesis.” The marrow may actually be more active than normal, but the cells it makes are defective and many die before ever reaching the bloodstream.
The defining problem is that your blood counts drop even though the marrow is working overtime. You end up with too few functional cells circulating in your blood, a condition called cytopenia. Depending on which cell lines are affected, you may be low in red cells, white cells, platelets, or all three.
Common Symptoms
Many people with MDS have no symptoms early on and only discover the condition through routine blood tests. When symptoms do appear, they stem directly from the shortage of healthy blood cells:
- Fatigue and shortness of breath from low red blood cells (anemia), the most common complaint
- Frequent or severe infections from low white blood cells
- Easy bruising, excessive bleeding, or tiny red spots under the skin from low platelets
- Unusual paleness, another sign of anemia
These symptoms tend to develop gradually and worsen over time as blood counts continue to drop.
Causes and Risk Factors
In most cases, there is no clear single cause. MDS develops when genes in a bone marrow stem cell mutate, but what triggers those mutations often remains unknown. Age is the strongest risk factor, with the vast majority of cases occurring in older adults.
About 5% of MDS cases are linked to previous cancer treatment. Chemotherapy and radiation therapy can damage bone marrow DNA, sometimes leading to MDS years later. Beyond treatment-related cases, there is strong evidence that occupational or environmental exposure to benzene (found in petroleum products, solvents, and cigarette smoke) and ionizing radiation raises risk. Tobacco smoking is an independently documented risk factor. Pesticide exposure has also been positively associated with MDS, though the evidence is less definitive than for benzene or radiation.
How MDS Is Diagnosed
Diagnosis starts with blood tests showing unexplained low counts, but confirming MDS requires a bone marrow biopsy. A small sample of marrow is examined under a microscope to look for abnormal cell shapes (dysplasia) and to count the percentage of immature cells called blasts. At least 10% of cells in a given lineage need to appear dysplastic for a formal diagnosis.
The blast percentage is particularly important. MDS is defined by a blast count below 20% in the bone marrow. Once blasts reach 20% or higher, the diagnosis shifts to acute myeloid leukemia (AML). Genetic testing is also performed to look for chromosomal abnormalities and specific gene mutations, which play a growing role in both classification and prognosis.
Subtypes and Classification
Not all MDS behaves the same way. The World Health Organization’s 2022 classification divides MDS into subtypes based on how the cells look, how many blasts are present, and increasingly, what genetic mutations are found. Three subtypes are now defined primarily by their genetics:
- MDS with an SF3B1 mutation, the most common gene mutation in MDS, is strongly linked to a specific finding called ring sideroblasts (iron-laden red cell precursors). This subtype tends to behave more indolently, with a lower risk of progressing to leukemia and generally better survival.
- MDS with isolated deletion of chromosome 5q also carries a relatively favorable outlook.
- MDS with mutated TP53 (specifically “multihit” TP53, meaning both copies of the gene are affected) is highly aggressive, genetically unstable, and progresses rapidly.
Other subtypes are grouped by the number of cell lines that look abnormal and by blast percentage. Subtypes with increased blasts (generally 5% to 19%) carry higher risk than those with lower blast counts.
Risk of Progressing to Leukemia
Between 30% and 40% of people with MDS will eventually progress to acute myeloid leukemia. This transformation happens when the abnormal clone accumulates enough additional genetic damage to push blast production past the 20% threshold. The timeline varies enormously. Some lower-risk subtypes remain stable for years, while aggressive forms like TP53-mutated MDS can evolve into AML within months.
Doctors use scoring systems to estimate an individual patient’s risk. The newest tool, called IPSS-M (Molecular International Prognostic Scoring System), combines blood counts, the percentage of bone marrow blasts, chromosomal findings, and mutations across 16 genes to generate a personalized risk score. Mutations in genes like TP53, RUNX1, and ASXL1 push risk scores higher, while an SF3B1 mutation generally lowers them.
Treatment Options
Treatment depends heavily on the subtype and risk category. For lower-risk MDS, the primary goal is improving blood counts and reducing the need for transfusions. For higher-risk disease, treatment aims to slow progression and extend survival.
For lower-risk patients with anemia, doctors typically start with medications that stimulate red blood cell production. When those stop working, other options include luspatercept, a drug approved in 2020 that helped 38% of patients with ring sideroblast MDS achieve at least 8 weeks free of transfusions in its pivotal trial (compared to 13% with placebo). Lenalidomide is particularly effective for patients with the 5q deletion subtype.
Azacitidine, a drug that works by reactivating genes silenced by the cancer, was approved for MDS in 2004 and remains a cornerstone of treatment for higher-risk disease. In clinical trials, about 45% of patients achieved independence from blood transfusions. However, most patients who respond eventually stop responding within about two years.
The only potentially curative treatment is a stem cell transplant, in which the diseased marrow is replaced with healthy donor marrow. This is an intensive procedure with significant risks, so it is generally reserved for younger, fitter patients with higher-risk disease. Many MDS patients, given the typical age at diagnosis, are not candidates for transplant.
Supportive care, including regular blood transfusions and antibiotics for infections, remains an important part of management for many patients throughout the course of the disease.
How Many People Are Affected
An estimated 10,000 or more people are diagnosed with MDS in the United States each year, though exact numbers are uncertain because MDS has historically been underreported. The true incidence is likely higher than official counts suggest, partly because the condition primarily affects older adults in whom blood count abnormalities may not always be thoroughly investigated. MDS is rare in younger people, and risk rises steadily with age.