Therapy-related myelodysplastic syndrome

Myelodysplastic syndrome (MDS) is a heterogeneous clonal disorder characterized by deregulation of apoptosis, dysplastic features in hematopoietic precursors, peripheral blood cytopenias and an increased risk for transformation to acute leukemia. Roughly 20% of MDS are therapy related (t-MDS), and this is considered an independent adverse prognostic factor.

This review based on a comprehensive literature search provides an overview on the main features of t-MDS, including its epidemiology, risk factors, molecular pathogenesis, prognostic classifications and therapy.

Increasing evidence points out that the most important event in t-MDS is genetic alterations in hematopoietic stem precursor cells, however, ineffective hematopoiesis may also result from abnormalities in the bone marrow microenvironment. Thus, novel views onto the processes of t-MDS are needed such as the osteohematology concept. On the other hand, the number of people living with and beyond cancer is increasing worldwide; thus, most emphasis should be placed on preventing secondary malignancies such as t-MDS. From this review, it becomes clear that we are in urgent need not only to deepen our understanding of the leukemogenesis mechanisms induced by exposure to chemotherapy and radiation but also to translate this knowledge into clinical strategies aimed at risk reduction.