Targeted Therapy in Myelodysplastic Syndrome

Managing patients with myelodysplastic syndrome (MDS) is a highly challenging endeavor. MDS appears to arise from intrinsic or acquired genetic defects in stem cells that confer a proliferative advantage to the malignant clone over normal stem cells. Recurrent chromosomal abnormalities are present in 40% to 70% of patients at diagnosis and in 95% of patients with treatment-related MDS. Until now, allogeneic stem cell transplantation and occasionally high-dose chemotherapy have been viewed as possibly curative options for patients with MDS disorders, but they are limited by the advanced age of most patients, concomitant co-morbidities, and/or in the case of stem cell transplantation the lack of donors. The escalating unraveling of numerous pathogenetic pathways in MDS has spurred development of novel targeted approaches for the treatment of these complex disorders. The recognition of the importance that epigentic phenomena play in the regulation of gene transcription led to the development of methylation inhibitors and histone deacetylase inhibitors in hematologic malignancies. Currently, these agents constitute the mainstay of therapy for MDS. Several agents with antiangiogenic properties have also been evaluated for the treatment of MDS, and immunotherapeutic approaches are under investigation for patients with MDS. Identifying the genes that are associated with recurrent chromosomal deletions and numerical abnormalities in patients with MDS, including studies and tests for haplo-insufficiency, are important directions to pursue in the future.