Myelodysplastic Syndromes

Myelodysplastic Syndromes


Myelodysplastic syndromes (MDS) are a group of hematologic malignancies of the pluripotent hematopoietic stem cells. These disorders are characterized by ineffective hematopoiesis, including abnormalities in proliferation, differentiation, and apoptosis. The overall clinical phenotype is peripheral cytopenias in the setting of a normocellular or hypercellular bone marrow and an increased risk for transformation to acute leukemia.

The incidence of MDS approximates 3 to 4 cases per 100,000 population per year, with 30 cases per 100,000 population per year in patients > 70 years old. It is estimated that approximately 10,000 to 15,000 new cases are diagnosed annually in the United States. Data on the epidemiology of MDS are now starting to emerge.



The overall incidence of MDS is slightly higher in males than in females (1.5 to 2:1).


The incidence of MDS increases with age, with a median age at diagnosis of about 70 years. MDS is rare in children; childhood cases are more frequently associated with monosomy of chromosome 7.

Etiology and Risk Factors

MDS is a clonal disorder of bone marrow stem cells. The vast majority of cases (80% to 90%) occur de novo, whereas 10% to 20% of cases are secondary. The etiology of de novo MDS is unclear. Exposure to radiation and/or cytotoxic agents is a recognized etiologic factor in secondary disease forms. Cumulative exposure to environmental toxins, genetic differences in leukemogen susceptibility and metabolism, and genomic senescence may contribute to disease pathogenesis in de novo cases.

Genetic Factors

It has been suggested that a genetic insult causes an irreversible alteration in the structure and function of the stem cell, with disruption of a multistep process involving control of cell proliferation, maturation, and interactions with growth factors; mutations of tumor-suppressor genes and proto-oncogenes; and deregulation of apoptosis.

Constitutional childhood disorders, such as Fanconi's anemia, Shwachman-Diamond syndrome, Down syndrome, neurofibromatosis, and mitochondrial cytopathies, have been associated with MDS and monosomy of chromosome 7. Recently, heritable mutations of the RUNX1 gene have been linked to familial cases of adult MDS.

Environmental Factors

Exposure to benzene and its derivatives may result in karyotypic abnormalities often seen in MDS and acute myelogenous leukemia (AML). Persons chronically exposed to insecticides and pesticides may have a higher incidence of MDS than the general population.

An increased incidence of MDS has been reported among smokers and ex-smokers, possibly linked to associated exposures to polycyclic hydrocarbons and radioactive polonium present in tobacco smoke.

An association of MDS with magnetic fields, alcohol, or occupational exposure to other chemicals has not been demonstrated.

Antineoplastic Drugs

Therapy-related myelodysplasia and therapy-related AML are recognized long-term complications of chemotherapy and radiotherapy. Therapy-related MDS usually develops 3 to 7 years after exposure to chemotherapy and is most frequently related to complete or partial loss of chromosomes 5 or 7 in patients previously treated with alkylating agents. Approximately 80% of cases of AML occurring after exposure to antineoplastic drugs, particularly alkylating agents, are preceded by MDS.

More than 85% of patients who develop chemotherapy-related leukemia or MDS have been exposed to alkylating agents. Patients exposed to nitrosoureas have a relative risk of developing MDS or AML of 14.4 and a 6-year actuarial risk of 4%. The mean cumulative risk of leukemia in patients exposed to epipodophyllotoxins (eg, etoposide and teniposide [Vumon]) is about 5% at 5 years. Most of these therapy-related leukemias are not preceded by a dysplastic phase and are associated with abnormalities in chromosome 11q23.

Autologous Bone Marrow Transplantation

Autologous Bone Marrow Transplantation (BMT) has also been associated with a 5-year actuarial risk of MDS of 15% (95% confidence interval [CI], 3.4%–16.6%). Fluorescence in situ hybridization analyses of pretreatment bone marrow specimens for informative cytogenetic markers indicate that these secondary myeloid malignancies derive from clones demonstrable before the transplant procedure. Prior therapy with fludarabine, older age, low CD34+ dose, and prolonged platelet reconstitution have been associated with the development of MDS or AML in patients with lymphoid malignancies after autologous stem cell transplantation (SCT).


By clicking Accept, you agree to become a member of the UBM Medica Community.