Description

• Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal stem cell disorders characterized by dysplastic cells and peripheral blood cytopenias: anemia, thrombocytopenia, and/or neutropenia
• Dysplasia refers to an abnormality of development or differentiation in specific cell lines within the bone marrow. MDS has similar pathological/cellular characteristics with acute myelogenous leukemia (AML). MDS has a lower percentage of blast (<20%) in the peripheral blood and bone marrow. MDS has the ability to transform into AML and is a premalignant condition.

Epidemiology

Incidence
The incidence in the United States is approximately 4.9 cases per 100,000 population and increases with age (majority >80 years)

Etiology and Pathophysiology

• MDS arises from mutations in hematopoietic stem cell lines due to various genetic/chromosomal abnormalities. Mutations are due to genetic abnormalities/damage to hematopoietic cells. Bone marrow is replaced with mutated cells which crowd out the normal cells and cause cytopenias of one or more cell lines.
• 80% of cases have no know cause or exposure.
• Environmental exposures: benzenes
• Chemotherapy and/or radiation therapy have been known to cause MDS which is classified as iatrogenic/secondary MDS. MDS can occur up to 10 years after treatment.
• De novo MDS or primary MDS may occur due to somatic mutations.
• Two classification systems of MDS exist.
  • World Health Organization (WHO)
  • International Consensus Classification (ICC) includes cytogenetics/karyotype abnormalities, degree of dysplasia, and percentage of blast. Recent changes: MDS/AML 10–19% blast, MDS with multiple hit PT53 mutations, and MDS due to cytotoxic agents (1).

Genetics

• Cytogenetic anomalies are observed in >90% of MDS patients which include translocations or aneuploidy (loss or gain of a chromosome).
• Deletion of the long arm of chromosome 5 (5q) is the most common abnormal karyotype due to either treatment-related MDS with 5q deletion associated with chemotherapeutic agents versus de novo isolated 5q deletion. Patients with 5q deletion due to exposure to chemotherapeutic agents usually have other cytogenetic abnormalities and/or TP53 mutations. These tend to have a poorer prognosis. Isolated 5q deletion without other cytogenetic anomalies generally have better prognosis. Other cytogenetic anomalies commonly studied include normal karyotype, deletion 7q (-7), and trisomy 8 and -Y (1).

Risk Factors

• Age: increased risk in patients >60 years old
• Tobacco use
• Chronic exposure to chemicals: benzene, pesticides, insecticides, and petroleum
• Prior chemotherapy or radiation therapy
• Inherited disorders: Fanconi anemia, Shwachman-Diamond syndromes, severe congenital neutropenia, and familial platelet disorder
• Autoimmune disorders such as vasculitis, connective tissue disease, and inflammatory arthritis
• End-stage renal disease on dialysis.