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PLoS One. 2012;7(8):e42080. doi: 10.1371/journal.pone.0042080. Epub 2012 Aug 6.

Aging of the microenvironment influences clonality in hematopoiesis.

Author information

1
Department of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany.

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.

PMID:
22879906
PMCID:
PMC3412859
DOI:
10.1371/journal.pone.0042080
[Indexed for MEDLINE]
Free PMC Article

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