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Stem cells

Competitive behaviour of cancer mutations

Nature Reviews Cancer volume 14, page 5 (2014)Cite this article

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Li et al. used a genetic mouse model in which inducible expression of Cre recombinase in the haematopoietic system activated a floxed allele of NrasG12D; NRAS is an oncogene that is commonly mutationally activated in various human leukaemias.

The activation of NrasG12D in haematopoietic stem cells (HSCs) increased their proliferation. Additionally, NrasG12D/+ HSCs outcompeted wild-type HSCs during their engraftment of a new recipient mouse in a transplantation assay and had increased long-term self-renewal following serial transplantation through multiple recipients. The increases in both proliferation and self-renewal were intriguing because HSC hyperproliferation that is caused by other mutations typically leads to the long-term exhaustion of HSC reserves.

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References

  1. Li, Q. et al. Oncogenic Nras has bimodal effects on stem cells that sustainably increase competitiveness. Nature http://www.dx.doi.org/10.1038/nature12830 (2013)

  2. Vermeulen, L. et al. Defining stem cell dynamics in models of intestinal tumor initiation. Science 342, 995–998 (2013)

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  1. Darren J. Burgess
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Burgess, D. Competitive behaviour of cancer mutations. Nat Rev Cancer 14, 5 (2014). https://doi.org/10.1038/nrc3652

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