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A<br />
B<br />
C<br />
LT-HSC<br />
CSC<br />
The <strong>Cancer</strong> Stem Cell hypothesis: Human tumors contain cells that are able to re-initiate tumor<br />
formation at distant sites (when metastases form) or when tumors relapse after chemotherapy.<br />
As illustrated in the Figure using acute myeloid leukemia as an example, these <strong>Cancer</strong> Stem Cells<br />
are self-renewing (CSC; panel B), and may phenotypically resemble the normal self-renewing<br />
stem cells (Long-term hematopoietic stem cells; LT-HSC; panel A) of the tissue from which they<br />
arise. However, <strong>Cancer</strong> Stem Cells may also have phenotypes of more committed progenitors<br />
(as exemplifi ed by the leukemic Common Myeloid Progenitor, or L-CMP; panel C), which have<br />
acquired ectopic self-renewal capacity, and thus able to perpetuate the malignant clone. Both<br />
normal and cancer stem cells reside at the top of a diff erentiation hierachy; however, while normal<br />
stem cells maintain the tissue by providing the cells which sustain its function <strong>Cancer</strong> Stem Cells<br />
give rise to defective progeny that when allowed to accumulate can lead to tissue failure.<br />
LT-HSC: Long-term hematopoietic stem cell; MPP: multipotent progenitor; CLP: common lymphoid<br />
progenitor; CMP: common myeloid progenitor; GMP: granulocyte-macrophage progenitor; MEP:<br />
megakaryocyte-erythroid progenitor.<br />
BIOLOGY<br />
“L-CMP”<br />
LT-HSC<br />
MPP<br />
+<br />
+<br />
CSC<br />
MPP*<br />
“L-CMP”<br />
+<br />
“CMP”<br />
CMP<br />
CLP<br />
CMP<br />
CLP<br />
MEP<br />
GMP<br />
MEP<br />
GMP<br />
MEP<br />
GMP<br />
Partially<br />
differentiated<br />
myeloid cells<br />
Partially<br />
differentiated<br />
myeloid cells<br />
Coordinator<br />
Claus Nerlov<br />
European Molecular Biology Laboratory<br />
Monterotondo, Italy<br />
nerlov@embl.it<br />
Partners<br />
Sten Eirik W. Jacobsen<br />
University of Lund<br />
Lund, Sweden<br />
Dominique Bonnet<br />
<strong>Cancer</strong> <strong>Research</strong> UK<br />
London, United Kingdom<br />
Tariq Enver<br />
MRC Molecular Hematology Unit<br />
Oxford, United Kingdom<br />
Roger Patient<br />
MRC Molecular Hematology Unit<br />
Oxford, United Kingdom<br />
Ole W. Petersen<br />
University of Copenhagen<br />
Copenhagen, Denmark<br />
Jon Tinsley<br />
Vastox<br />
Oxford, United Kingdom<br />
Project number<br />
LSHC-CT-2006-037632<br />
EC contribution<br />
€ 1 900 000<br />
Duration<br />
36 months<br />
Starting date<br />
01/01/2007<br />
Instrument<br />
STREP<br />
Project website<br />
www.embl-monterotondo.it/<br />
research/projects/nerlov/<br />
eurocsc.html<br />
39
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