title: Aging of the microenvironment influences clonality in hematopoiesis.
abstract: The mechanisms of the age-associated exponential increase in the incidence of leukemia are not known in detail. Leukemia as well as aging are initiated and regulated in multi-factorial fashion by cell-intrinsic and extrinsic factors. The role of aging of the microenvironment for leukemia initiation/progression has not been investigated in great detail so far. Clonality in hematopoiesis is tightly linked to the initiation of leukemia. Based on a retroviral-insertion mutagenesis approach to generate primitive hematopoietic cells with an intrinsic potential for clonal expansion, we determined clonality of transduced hematopoietic progenitor cells (HPCs) exposed to a young or aged microenvironment in vivo. While HPCs displayed primarily oligo-clonality within a young microenvironment, aged animals transplanted with identical pool of cells displayed reduced clonality within transduced HPCs. Our data show that an aged niche exerts a distinct selection pressure on dominant HPC-clones thus facilitating the transition to mono-clonality, which might be one underlying cause for the increased age-associated incidence of leukemia.
authors.affiliation: Department of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany.
authors.forename: Virag
authors.initials: V
authors.lastname: Vas
authors.forename: Katharina
authors.initials: K
authors.lastname: Senger
authors.forename: Karin
authors.initials: K
authors.lastname: Dörr
authors.forename: Anja
authors.initials: A
authors.lastname: Niebel
authors.forename: Hartmut
authors.initials: H
authors.lastname: Geiger
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002469:Cell Separation; D060833:Cellular Microenvironment; D016922:Cellular Senescence; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL