Gene expression profiling of pre-HPCs derived from CML-iPSCs

Properties of cancer stem cells (CSC) involved in drug-resistance and relapse have significant effect on clinical outcome. Although tyrosine kinase inhibitors (TKIs) have dramatically improved survival of patients with chronic myelogenous leukemia (CML), TKIs have not fully cure CML due to TKI-resistant CML stem cells. Moreover, the relapse after discontinuation of TKIs has not been predicted in CML patients with best TKI-response. In our study, pre-hematoopoietic progenitor cells (pre-HPCs), a model of CML stem cells derived from CML-iPSCs identified a novel antigen of TKI-resistant CML cells. Even in the fraction reported as TKI-sensitive, the antigen+ cells showed TKI-resistance in CML patients. In addition, residual CML cells in patients with optimal TKI-response were concentrated in the antigen+ population. Imatinib induced gene expression in pre-HPCs from CML-iPSCs and normal-iPSCs and differentiated cells (DCs) from CML-iPSCs was measured at 6 hours after exposure to doses of 2.5 microM. Three independent experiments were performed using different clones for each experiment.