Advancements in the molecular pathogenesis of myelodysplastic syndrome

Abstract

Purpose of review: Myelodysplastic syndrome is an important hematological malignancy affecting the expanding aged population. Our understanding of the biology of this disease has been limited by the heterogeneous clinicopathological features, difficulty in creating animal models, and paucity of evidence linking molecular abnormalities to disease pathogenesis. The importance of new advances in myelodysplastic syndrome will be discussed in this review.

Recent findings: Heightened awareness of the myelodysplastic syndrome burden has garnered rising interest in the development of new treatment strategies and investigation of the molecular basis of this complex disease. A multistep process explains the heterogeneity observed in myelodysplastic syndrome better than a single event, whereby multiple biological forces culminate in telomere erosion and genomic instability. Intrinsic genetic factors within myeloid progenitors along with extrinsic factors in the microenvironment may foster clonal selection. Specific targeted intervention at critical stages along this multistep pathway, prior to acute myeloid leukemia transformation, may produce the best clinical outcome.

Summary: Newly identified molecular defects, the creation of animal models, and several advancements in our understanding of the molecular pathogenesis have dramatically improved diagnostic and therapeutic potential of myelodysplastic syndrome.