Dynamic Evolution of Leukemia Stem Cells both at the Carcinogenesis and Relapse Go Yoshida, Tokyo Medical and Dental University 27 March 2015 As mentioned in this review article, leukemia stem cells undergo drastic change orchestrated with somatic genetic mutations and epigenetic alteration. Leukemia stem cells are derived from HSCs localized in the niche under the conditions of hypoxia, chronic inflammation, accumulated ROS, all of which are responsible for the carcinogenesis. Niche factors are also affected to induce the aberrant proliferation of pre-malignant cells. For instance, PNH-anaplastic anemia syndrome as well as MDS is considered to be pre-malignant disorders to induce leukemia. Furthermore, the molecular-targeting drugs characterized by imatinib cause the activation of alternative signaling pathways, which results in the acquisition of adaptive resistance to conventional anti-cancer therapy. We have to keep in mind that both at the carcinogenesis and latent relapse, sub-population of leukemic cells each of which harbor leukemic stem-like cells undergo evolution with the genetic or epigenetic background under the selection pressure. Selection pressure includes anti-cancer therapy, which is why medical intervention sometimes enhances the proliferation activity of quiescent leukemia stem cells. Competing interests No Competing Interests Exist.