Reprogramming technology reveals genetic and functional diversity of subclones in myelodysplastic syndromes.

ABSTRACT

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell diseases characterized by inefficient hematopoiesis and poor prognosis. There are currently no useful tools for identifying new therapeutic targets of MDS mainly because of a lack of good disease models. Although massive parallel sequencing studies have revealed several MDS-specific genomic alterations that are different from those of de novo acute myeloid leukemia (AML), the relationships between the genetic architecture and pathophysiology in MDS remain poorly understood. We successfully generated multiple iPS cell lines (MDS-iPSC lines) from several patients with either MDS or secondary AML that progressed from MDS. We assessed the hematopoietic differentiation potential of the established MDS-iPSC lines and identified stage-specific maturation defects with graded severity. The MDS-iPSC lines could be a useful tool for elucidating the subclonal diversity, pathogenesis, and clonal evolution of MDS as well as for identifying new therapeutic compounds.