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Cytogenetics and molecular genetics of myelodysplastic syndromes

Yanming Zhang, MD
Michelle M Le Beau, PhD
Section Editor
Richard A Larson, MD
Deputy Editor
Alan G Rosmarin, MD


The myelodysplastic syndromes (MDS) encompass a series of hematologic conditions characterized by chronic cytopenias (anemia, neutropenia, thrombocytopenia) accompanied by abnormal cellular maturation. As a result, patients with MDS are at risk for symptomatic anemia, infection, and bleeding, as well as progression to acute myeloid leukemia (AML), which is often refractory to standard treatment.

The pathobiology of MDS is complex and not fully understood; however, alterations in the function of the bone marrow microenvironment, or niche, as well as the hematopoietic stem cells have been implicated. The development of MDS involves a series of genetic changes in a hematopoietic stem cell. These changes alter normal hematopoietic growth and differentiation, resulting in an accumulation of abnormal, immature myeloid cells in the bone marrow and the impairment of normal hematopoiesis. Advances in the identification of recurring chromosomal abnormalities and gene alterations have provided insight into the pathobiology of MDS.

Specific cytogenetic abnormalities identified by karyotype analysis or fluorescence in situ hybridization (FISH) analysis have prognostic significance for patients with primary MDS and affect treatment planning. Certain gene mutations also confer prognostic significance in adult patients with MDS, but it is not yet clear how to incorporate these changes into treatment planning. Even those patients without obvious abnormalities detected by karyotypic analysis, FISH, or gene mutation analyses likely have abnormalities in gene expression profiles or have acquired copy number alterations that may help to identify genes important for the pathogenesis of MDS.

Characteristic chromosomal abnormalities have also been identified in patients who developed MDS or AML (often preceded by MDS) after chemotherapy and/or radiation therapy for an earlier disorder, such as Hodgkin lymphoma, non-Hodgkin lymphoma (NHL), or a solid tumor, as well as non-malignant disorders, such as rheumatoid arthritis, or following organ transplantation (table 1). This subject is discussed separately. (See "Cytogenetics in acute myeloid leukemia", section on 'Therapy-related myeloid neoplasms (t-MDS/t-AML)'.)

The cytogenetic and molecular genetic features of primary MDS and the use of genetic studies in predicting both progression to AML and survival will be reviewed here. An overview of cytogenetic abnormalities in hematologic malignancies (including definitions, methods of detection, the genetic consequences of chromosomal translocations) and a more detailed discussion of the prognosis of MDS are presented separately. (See "Prognosis of the myelodysplastic syndromes in adults" and "General aspects of cytogenetic analysis in hematologic malignancies" and "Chromosomal translocations, deletions, and inversions".)

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Literature review current through: Nov 2017. | This topic last updated: Nov 02, 2016.
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