leukemia have demonstrated this possibility
( 11). Therefore, markers that are inextricably
linked to cellular signaling pathways that
control extensive cancer cell proliferation and
self-renewal should be more predictably associated
with tumor-initiating potential than
markers associated with normal differentiation.
However, most studies assessing cellular
permissiveness to transformation have been
performed on mouse cells, which are easier
to transform than human cells. Further studies
are required to defi ne the permissiveness
of various human cell types. Furthermore,
studies such as that of Friedmann-Morvinski
et al. introduce multiple genetic abnormalities
simultaneously, so mutations could accumulate
in tissue-specifi c stem cells until the
fi nal lesion necessary for tumor development
is acquired in one of many transformable cell
types; that cell type then becomes the cell of
origin for that cancer.
The genetic makeup of a malignancy correlates
with clinical outcome and can therefore
be useful in predicting prognosis and
planning treatment. In addition to the impact
of the genetic lesions themselves, the epigenetic
state of cells within the cancer, perhaps
infl uenced by the cell of origin, likely contributes
to the clinical properties, including drug
resistance ( 12). Gene expression profi ling of