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Targeting Leukaemia Stem Cells

 
  April, 12 2006 9:07
your information resource in human molecular genetics
 
     
Cancer stem cells - cells thought to initiate and maintain tumours - share many properties with normal stem cells, making it difficult to design cancer treatments that effectively target cancer stem cells without killing normal stem cells. This is problematic as damaging, for example, haematopoietic stem cells during the treatment of leukaemia would severely compromise the immune system.

In a paper published online on April 06, 2006, by Nature, Sean Morrison and colleagues study a tumour suppressor protein frequently inactivated in leukaemia and other cancers. Called PTEN, this protein normally inhibits the phosphatidylinositol-3-OH kinase (PI(3)K) signalling pathway and its downstream effector mTOR, thus limiting cell proliferation and survival.

The researchers deleted Pten in blood cells of mice and found that although this led to the development of leukaemias, normal haematopoietic stem cells became depleted because they lost the ability to maintain themselves. Treatment of these mice with the mTOR inhibitor rapamycin prevented the generation of leukaemic stem cells and leukaemia development, and reduced the number of leukaemia stem cells in already established leukaemias. Moreover, rapamycin restored the function of normal haematopoietic stem cells, including their ability to replenish immune cells in bone-marrow-depleted mice. Therapeutically targeting pathways that distinguish between normal stem cell self-renewal and cancer stem cell function in the same tissue may make it possible to target tumours without damaging normal stem cells.

CONTACT

Sean Morrison (University of Michigan, Ann Arbor, MI, USA)
E-mail: seanjm@umich.edu

Abstract available online.

(C) Nature press release.


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