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Leukaemia

A TALE of one Meis

Nature Reviews Cancer volume 7, pages 894–895 (2007)Cite this article

The authors first expressed 12 different MLL fusion proteins in primary mouse myeloid progenitor cells and found that Meis1 expression levels correlated with the latencies observed for leukaemias harbouring the various MLL fusion oncogenes. That is, higher Meis1 expression was observed in cells expressing MLL oncogenes that induce leukaemias with a shorter latency. In addition, transformation assays using fetal liver (FL) cells derived from Meis1−/− mice showed that these cells could not be transformed by MLL oncogenes, but transformation could be rescued by the expression of exogenous Meis1. Furthermore, expression of Meis1 short hairpin RNAs or a dominant-negative MEIS1 in wild-type FL cells expressing MLL fusions impaired clonogenic capacity. These data indicate that MEIS1 is involved in both the initiation and maintenance of MLL-mediated transformation.

Does MEIS1 influence leukaemo-genesis in vivo? Myeloid progenitors expressing an MLL fusion oncogene and either Meis1 (MLL/Meis1) or an empty vector (MLL/v) were transplanted in equal numbers of colony-forming cells (CFCs) into syngeneic mice. The authors found that both cohorts of mice developed similar leukaemias, but leukaemias in mice transplanted with MLL/Meis1 cells had much shorter latencies. This correlated with reduced differentiation and increased proliferation, which seemed to be due to perturbation of the BMI1–INK4a axis. Furthermore, the numbers of CFCs in the spleens of leukaemic mice (which have the properties of LSCs) were sevenfold higher for MLL/Meis1 leukaemias than for MLL/v leukaemias. Thus, Meis1 serves a rate-limiting role in MLL leukaemogenesis.

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References

ORIGINAL RESEARCH PAPER

  1. Wong, P., Iwasaki, M., Somervaille, T. C., So, C. W., & Cleary, M. L. Meis1 is an essential and rate-limiting regulator of MLL leukemia stem cell potential. Genes Dev. 17 October 2007 (doi: 10.1101/gad.1602107)

FURTHER READING

  1. Krivtsov, A. V. & Armstrong, S. A. MLL translocations, histone modifications and leukaemia stem-cell development. Nature Rev. Cancer 7, 823–833 (2007)

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Authors
  1. Sarah Seton-Rogers
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Seton-Rogers, S. A TALE of one Meis. Nat Rev Cancer 7, 894–895 (2007). https://doi.org/10.1038/nrc2280

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  • DOI: https://doi.org/10.1038/nrc2280

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