Modeling of hematologic malignancies by iPS technology

Abstract

Induced pluripotent stem cells (iPSCs) can be generated from various types of cells with transduction of defined transcription factors. Patient-derived iPSCs are becoming commonly utilized for understanding the molecular pathways involved in disease and for the development of novel targeted therapies. With the use of patient-derived iPSCs differentiated to specific-lineage cells, the potency and toxicity of drug candidates can be evaluated. In the past, patient-derived iPSCs were mainly established from patients of inherited hematologic diseases, followed by the expansion of target to acquired diseases like myeloproliferative neoplasms. Thanks to the rapid development of novel genome editing technologies, we can now utilize genetically modified and unprocessed iPSCs more readily than before. These technologies, which enable us to modulate genetic status or even chromosome structure at the right time, could help the elucidation of pathogenesis of hematologic diseases. If iPSC-derived hematopoietic cells are to be robustly reconstituted in vivo as a consequence of the development of reprogramming and conversion technology, research on leukemic stem cells must be widely promoted. Therefore, iPSC technology has great potential on oncology research using patient samples.