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Hematology 2004
© 2004 The American Society of Hematology

Myelodysplastic Syndromes

Alan F. List, James Vardiman, Jean-Pierre J. Issa and Theo M. DeWitte

Abstract

The development of new therapeutic strategies for myelodysplastic syndromes (MDS) has gained new momentum fueled by improved characterization of the disease’s natural history and biology and by the recent US Food and Drug Administration (FDA) approval of the first agent with an indication for MDS. By integrating morphologic and cytogenetic features with greater discriminatory power, the World Health Organization (WHO) has refined the classification of these stem cell malignancies and enhanced its prognostic utility. Recognition that the malignant phenotype, which characterizes MDS, may arise from mechanistically diverse biological processes has raised new awareness that treatment strategies must be tailored to the pathobiology of the disease. Therapeutics targeting chromatin structure, angiogenesis and the microenvironment that nurtures the MDS phenotype have demonstrated remarkable activity and offer an opportunity to alter the natural history of the disease. This chapter provides an overview of recent developments in the characterization of MDS from the microscope to the laboratory and the translation of these findings into promising therapeutics.

In Section I, Dr. James Vardiman reviews the cytogenetic abnormalities that characterize MDS, their clinical and pathologic significance, and the application of the WHO classification. In Section II, Dr. Alan List reviews treatment goals driven by prognostic variables and biological features of the disease that have led to promising small molecule, selective therapeutics. In Section III, Dr. Jean-Pierre Issa provides an overview of epigenetic events regulating gene expression, which may be exploited therapeutically by chromatin remodeling agents. In Section IV, Dr. Theo DeWitte discusses new developments in hematopoietic stem cell transplantation, including reduced-intensity and myeloablative approaches.


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Copyright © 2004 by the American Society of Hematology.