title: Genetic and epigenetic alterations that drive leukemic stem cell self-renewal.
abstract: Acute myeloid leukemia has emerged as a paradigm for the concept of the cancer stem cell. This hypothesis presumes that the disease is maintained by a rare population of leukemia-initiating stem cells which have acquired genetic or epigenetic changes. It is most likely that a single (epi)genetic event will not be sufficient to cause leukemia, but that a number of sequential events are required. Similar to normal hematopoietic stem cells, both intrinsic as well as extrinsic factors that arise from the bone marrow niche, provide essential cues that regulate cell fate decisions such as leukemic stem cell self-renewal and differentiation. In this chapter, we will review the current understanding of genetic and epigenetic abnormalities that underlie the process of leukemic transformation, and will discuss which events potentially co-operate to induce leukemia.
authors.affiliation: Department of Hematology, Cambridge Institute for Medical Research, Hills Road, Cambridge, CB2 OXY, UK.
authors.forename: Vincent
authors.initials: V
authors.lastname: van den Boom
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Horton
authors.forename: Jan Jacob
authors.initials: JJ
authors.lastname: Schuringa
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D057890:Epigenomics; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology*