Genetic and epigenetic alterations in myelodysplastic syndrome

Myelodysplastic syndrome (MDS) is a clonal disorder characterized by dyshematopoiesis and high susceptibility to acute myeloid leukemia (AML). As patients with MDS have widely variable prognosis, we need to stratify them according to chromosomal abnormalities, genetic alterations, and epigenetic deregulations associated with progression to AML in order to treat these patients appropriately. Recently, evidence has been accumulating on the molecular mechanism underlying self-renewal of stem cells. Specifically, we have been focusing on Polycomb-group (PcG) genes, which play an important role in supporting self-renewal. There is emerging evidence indicating that the PcG complexes are indispensable for sustaining stem cell activity and cancer stem cells. We have reported that the expression of BMI1, a member of PcG, in hematopoietic stem cells or progenitor cells predicts the prognosis of patients with MDS and progression to acute leukemia. And recent genome-wide analyses showed that major transcriptional regulators governing development are under the regulation of PcG complexes. Thus PcG not only provides a molecular marker for monitoring disease progression of MDS, but also provides a clue for elucidating a molecular mechanism underlying the disease progression, which may help in the development of a new therapeutic strategy against MDS. Herein, we describe cytogenetic, genetic and molecular aberrations in MDS, focusing on epigenetic alterations through PcG.