title: [Leukemia stem cell and clonal evolution].
abstract: The introduction of next generation sequencing technology has greatly broadened our view on the genetic landscape of hematological malignancies. The first comprehensive experiment of acute myeloid leukemia(AML) using genome-wide analysis has also shed light on the clonal evolution of AML, which seems to have been underestimated. It is now possible to precisely define clonal size and selection at different stages. This approach demonstrated that AML at diagnosis is either monoclonal or oligoclonal, harboring a selected number of genetically defined subclones. Furthermore, targeted deep sequencing of diagnosis and relapse pairs revealed that founding clones or subclones present at diagnosis obtain some additional mutations that contribute to clonal expansion and/or chemoresistance. Some subclones may be eradicated by treatment, whereas others are resistant to chemotherapeutic agents and ultimately grow out. The molecular heterogeneity in AML will have a great impact on the development of targeted therapies.
authors.forename: Akihide
authors.initials: A
authors.lastname: Yoshimi
authors.forename: Mineo
authors.initials: M
authors.lastname: Kurokawa
mesh_terms: D060965:Clonal Evolution; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D009154:Mutation