Affiliations: Terry Fox Laboratory, British Columbia Cancer Agency,
Vancouver, BC, Canada V5Z 1L3 | Department of Medical Genetics, University of British
Columbia, Vancouver, BC, Canada V5Z 1L3 | Department of Medicine, University of British
Columbia, Vancouver, BC, Canada V5Z 1L3 | Department of Pathology and Laboratory Medicine,
University of British Columbia, Vancouver, BC, Canada V5Z 1L3
Abstract: Chronic myeloid leukemia (CML) is a clonal multi-step
myeloproliferative disease that is initially produced and ultimately sustained
by a rare subpopulation of BCR-ABL^{+} cells with
multi-lineage stem cell properties. These BCR-ABL^{+}
CML stem cells are phenotypically similar to normal hematopoietic stem cells
which are also maintained throughout the course of the disease at varying
levels in different patients. Defining the unique properties of the leukemic
stem cells that produce the chronic phase of CML has therefore had to rely
heavily on access to samples from rare patients in which the stem cell
compartment is dominated by leukemic elements. Here we review past and ongoing
approaches using such samples to identify biologically and clinically relevant
biomarkers of BCR-ABL^{+} stem cells that explain their
unusual biology and that may help to design, or at least predict, improved
treatment responses in CML patients. These studies are of particular interest
in light of recent evidence that chronic phase CML stem cells are not only
innately resistant to imatinib mesylate and other drugs that target the BCR-ABL
oncoprotein, but are also genetically unstable.
