Targeted Therapy in Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) represent a group of clonal diseases characterized by defective hematopoiesis, increased apoptosis, and risk of transformation to acute leukemia. Incidence increases with age, with 4.3-4.6 new cases per 100,000 persons per year. Approximately 10-20% patients will suffer transformation into AML with dismal prognosis. Despite increasing knowledge in the biology of the disease, MDS remains an important challenge due to the complex array of pathways participating in disease initiation and evolution. Morphological and clinical diversity further increases MDS complexity. Mutations in different pathways including kinase signaling (FLT3, RAS, JAK2, KIT, CBL), transcription factors (TP53, RUNX1, and ETV6), epigenetic modulators (IDH 1/2, TET2, DNMT3A, EZH2, ASXL1), and spliceosome machinery (SF3B1, U2AF1, SRSF2, ZRSR2) have been systematically described in MDS. Other biological events have also been described in disease pathogenesis including miRNA, innate immunity, and microenvironment alterations. An array of different drugs directed at various disease processes are under development with promising results.