Wednesday, January 21, 2009

Turning Stem Cells Into Cancer

An interesting new paper (Open Access, click away!!!) exploring the cancer stem cell hypothesis, describing to my knowledge the first transgenic cancer model to be derived by specifically targeting a normal stem cell population. The Spanish group of Maria Perez-Caro et al. show that they can induce chronic myeloid leukemia (CML) in mice by introducing the infamous bcr-abl oncogene (a gene encoding an aberrent fusion protein known to drive the human disease), specifically into Sca1+ normal hematopoietic stem cells.

They go on to use the model to investigate an important corollary of the cancer stem cell hypothesis, which postulates that residual CSCs are responsible for disease remission during/following therapy. They show that their CML mice cannot be cured with the bcr-abl targeted inhibitor STI571/Gleevec, whereas ablation of the Sca1+ stem cell compartment is sufficient to eliminate the disease. Therapeutically speaking they cheated a bit here by simply engineering a suicide gene into the oncogene cassette, but it's a start. It would be nice to see whether a therapeutically relevant approach to CSC depletion (ie anti-Sca-1 MAb) would also be able to eliminate the disease in their model.


Anonymous said...

From what I can tell from briefly skimming the article they did not test whether BCR-ABL behaves similarly in sca-1 negative cells (They couldn't because of the transgene design). Then how are we sure that the residual disaes has anything to do with "stemness".