Induced pluripotent stem cell models of myeloid malignancies and clonal evolution

Reprogramming of cells from patients with genetic disorders to pluripotency is a promising avenue to understanding disease biology. A number of induced pluripotent stem cell (iPSC) models of inherited monogenic blood disorders have been reported over the past decade. However, the application of iPSCs for modeling of hematological malignancies has only recently been explored. Blood malignancies comprise a spectrum of genetically heterogeneous disorders marked by the acquisition of somatic mutations and chromosomal aberrations. This genetic heterogeneity presents unique challenges for iPSC modeling, but also opportunities to capture genetically distinct states and generate models of stepwise progression from normal to malignant hematopoiesis. Here we briefly review the current state of this field, highlighting current models of acquired pre-malignant and malignant blood disorders and clonal evolution, and challenges including barriers to reprogramming and differentiation of iPSCs into bona fide hematopoietic stem cells.