Human acute leukemia induced pluripotent stem cells: a unique model for investigating disease development and pathogenesis

Human cancer is generally studied once the full transformation events have taken place. Accordingly, investigations of key questions about early cancer pathogenesis, such as cell-of-origin, target cell for transformation, developmental impact of cancer-specific genetic insults, lineage affiliation of fusion genes and intratumor heterogeneity, are not amenable using patient samples (1,2). It is becoming increasingly clear that for almost all cancers, the cancer bulk displays features of normal tissue organization, where cancer stem cells (CSCs) sit at the top of the hierarchical structure and drive tumor growth and evolution (3). Therefore, the establishment of effective disease models to study the developmental impact of cancer-specific genetic aberrations on human stem cell fate is in high demand.