Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplastic disorders of hematopoietic stem cell origin, characterized by abnormal differentiation and maturation of myeloid cells, pathological hematopoiesis and ineffective hematopoiesis in one or more blood lines, refractory hematocrit reduction, and high risk of transformation to acute myeloid leukemia (AML). MDS is common in the elderly, with an annual incidence of about 3/100,000 to 3.5/100,000, with an increasing trend with age, and a median age of 60 to 75 years. About 80% of MDS are over 60 years of age, slightly more males than females at 1.2:1, and the annual incidence rate is 4.5/100,000 for males and 2.7/100,000 for females. MDS was named by the French-American-British (FAB) Collaborative Group in 1982 and includes the previously reported refractory anemia, iron loss-utilizing anemia, pre-leukemia (PL), and smoldering leukemia. I. Etiology and pathogenesis The hematopoietic stem cell clone of MDS can involve the granulocytic, erythroid and megakaryocytic lineages. The abnormal clonal cells have impaired differentiation and maturation in the bone marrow and appear morphologically pathologic hematopoiesis, which is destroyed in the bone marrow in situ or soon after release into the blood, resulting in ineffective hematopoiesis. A few genetic risk factors for MDS exist, such as Down syndrome and Fanconi anemia can increase the risk of developing MDS. Gene polymorphisms affect the metabolic activity of enzymes in vivo for toxic chemicals and chemotherapeutic agents and determine individual differences in susceptibility to MDS. Increased risk of myeloid malignancies has been reported for cytochrome p4503A, glutathione-S-transferase, and NAD(P)H gene polymorphisms. Radiation, smoking, pesticides, organic solvents, and heavy metals, which are associated with the development of primary MDS. Secondary MDS is seen in close exposures to alkylating agents, radiation, and benzene. Patients with lymphoma are at higher risk of developing secondary MDS and AML after long-term treatment and have a poor prognosis. Non-random karyotypic abnormalities are seen in about 50% of MDS, commonly +8, -7/7q-, -5/5q-, 20q-, -Y, i(17q)/t(17p), etc. Some patients have more than two chromosomal abnormalities. The genetic mutations and abnormalities often involved in MDS are: epigenetics (e.g. TET2, DNMT3A gene), spliceon complex (e.g. SF3B1 gene), tyrosine kinase pathway (e.g. NRAS gene), transcription factors (e.g. RUNX1 gene), and others such as P53 oncogene, which are involved in the development and disease progression of MDS. The bone marrow microenvironment of MDS, such as cytokine microenvironment, apoptosis rate and microvessel density interact to form another pathway associated with MDS disease progression, causing increased apoptosis of CD34+ progenitor cells in the lower risk early stages, while decreasing their apoptosis rate in the late stages. And may be accompanied by proliferative genetic events that influence the progression of MDS to AML.