Abstract

Priya Rai, Pradeep Mehra, Ragini Kumari, Radhika Vishwkarma and Pushpendra K. Khangar*

ABSTRACT

Myelodysplastic syndromes (MDS/ Myelodysplasia) are a group of clonal hematologic disorder, which combine ineffective hematopoiesis and evolution to acute myeloid leukemia. Significant progress has been made in the understanding of the disease pathogenesis, diagnostics and classification. Promising new agents and innovative therapeutic strategies are currently used. In this article we will review these achievements and their impact on the treatment of MDS. Once thought to be rare disorders, the myelodysplastic syndromes (MDS) are now recognized as among the most common hematological neoplasms, probably affecting >30 000 patients per year in the United States. US regulatory approval of azacitidine, decitabine, and lenalidomide between 2004 and 2006 seemed to herald a new era in the development of disease-modifying therapies for MDS, but there have been no further drug approvals for MDS indications in the United States in the last 8 years. The available drugs are not curative, and few of the compounds that are currently in development are likely to be approved in the near future. As a result, MDS diagnoses continue to place a heavy burden on both patients and health care systems. Incomplete understanding of disease pathology, the inherent biological complexity of MDS, and the presence of comorbid conditions and poor performance status in the typical older patient with MDS has been major impediments to development of effective novel therapies. Here we discuss new insights from genomic discoveries that are illuminating MDS pathogenesis, increasing diagnostic accuracy, and refining prognostic assessment, and which will one day contribute to more effective treatments and improved patient outcomes. The pathogenesis of MDS involves abnormalities of the MDS clone itself such as abnormal apoptosis, signalling or epigenetic regulation and abnormalities of the microenvironment such as immune deregulation or increased angiogenesis, which represent potential therapeutic targets. There is currently no standard treatment for MDS and allogeneic stem cell transplantation remains the only curative strategy. However, besides conventional chemotherapy and growth factors, new agents including hypomethylating agents, antiangiogenic drugs, immune modulatory agents have proved effective. KEYWORDS: Myelodysplastic syndromes, Anemia, Luspatercept-Aamt.