Myelodysplastic Syndromes

Abstract

SynopsisThe myelodysplastic syndromes are a diverse group of clonal stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and an increased propensity to evolve to acute myeloid leukemia. The molecular pathogenesis of these disorders is poorly understood, but recurring chromosomal abnormalities occur in ~50% of cases, and are the focus of much investigation. The availability of newer molecular techniques has allowed the identification of additional genetic aberrations, including mutations and epigenetic changes of prognostic and potential therapeutic importance. This review will focus on the key role of cytogenetic analysis in MDS in the context of the diagnosis, prognosis, and pathogenesis of these disorders.Keywords myelodysplastic syndromes; cytogenetics; molecular genetics; diagnosis; prognosis; classification IntroductionThe myelodysplastic syndromes (MDS) include a large spectrum of clonal hematopoietic stem cell disorders that are characterized by peripheral cytopenia(s), morphologic dysplasia, ineffective hematopoiesis, and a variable propensity to transform to acute myeloid leukemia (AML). 1,2 The cytopenia can be limited to a single cell line resulting in anemia, This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript thrombocytopenia, or neutropenia, and can be chronic and somewhat indolent, or profound involving all three lineages with life-threatening consequences. The morphologic dysplasia associated with the ineffective hematopoiesis may be subtle and difficult to recognize but, in some cases, it can be impressive and evident in both the bone marrow and peripheral blood. The variable increase in blasts relates, in part, to the risk for transformation to AML, although progression is not solely dependent on the blast percentage. MDS is a disease of older adults with a median age at diagnosis of ~70 years 3 . Other risk factors for the development of MDS include tobacco use and exposure to solvents, such as benzene and agricultural chemicals. In ~10-15% of cases, the disease arises as a late complication of cytotoxic therapy (radiotherapy and/or chemotherapy) for a prior disorder, and is referred to as a therapy-related myeloid neoplasm (t-MN). MDS is frequently associated with clonal cytogenetic abnormalities, of significant prognostic 4,5 and emerging therapeutic importance. An in-depth analysis of some of these is providing significant insights into underlying molecular alterations, which may hold clues to unraveling the pathogenesis of these disorders. This review will focus on the ...