Melodysplastic Syndromes

In the recent years, the discovery of a series of mutations in patients with myeloid malignancies has provided insight into the pathogenesis of myelodysplastic syndromes (MDSs), myeloproliferative neoplasms (MPNs), and acute myeloid leukemia (AML). Among these alterations have been mutations in genes, such as IDH1/2, TET2, DNMT3A, and EZH2, which appear to affect DNA and/or histone lysine methylation. Large clinical correlative studies are beginning to decipher the clinical importance, prevalence, and potential prognostic significance of these mutations. Additionally, burgeoning insight into the role of epigenetics in the pathogenesis of myeloid malignancies has prompted increased interest in development of novel therapies which target DNA and histone posttranslational modifications. DNA demethylating agents have been demonstrated to be clinically active in a subset of patients with MDS and AML and are used extensively. However, newer, more specific agents which alter DNA and histone

Myelodysplastic syndromes (MDS) are a group of clonal hematopoetic disorders marked by ineffective hematopoiesis, peripheral cytopenias, and an increased risk of transformation to acute myeloid leukemia. Multiple processes govern hematopoietic progenitor proliferation and natural differentiation into mature myeloid elements. Molecular events that disrupt any of these processes have the potential to lead to ineffective hematopoiesis and an MDS phenotype. Recent advances in genomic analysis have identified a number of new genes that may be involved. The molecular description of MDS will lead to better understanding, classification, and treatment of this disease.

Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by dysplasia in one or more cell lines and increased risk of development of acute myeloid leukemia (AML). The current diagnostic approach to MDS includes peripheral blood and bone marrow morphology to evaluate abnormalities of peripheral blood cells and hematopoietic precursors; bone marrow biopsy to assess marrow cellularity, fibrosis, and topography; and cytogenetics to identify non-random chromosomal abnormalities. The 2008 World Health Organization (WHO) classification currently provides the best diagnostic approach to MDS and also has considerable prognostic relevance. The WHO classification-based prognostic scoring system (WPSS) is able to classify MDS patients into five risk groups showing different survivals and probabilities of leukemic evolution. The WPSS is able to predict survival and leukemia progression at any time during follow-up, and can therefore be used for implementing risk-adapted treatment