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Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 1056-1065
Myeloma progenitors in the blood of patients with aggressive
or minimal disease: engraftment and self-renewal of primary
human myeloma in the bone marrow of NOD SCID mice
Linda M. Pilarski,
Gail Hipperson,
Karen Seeberger,
Eva Pruski,
Robert W. Coupland, and
Andrew R. Belch
From the Departments of Oncology and Pathology, University of
Alberta, Edmonton, Alberta, Canada.
The myelomagenic capacity of clonotypic myeloma cells in G-CSF
mobilized blood was tested by xenotransplant. Intracardiac (IC)
injection of NOD SCID mice with peripheral cells from 5 patients who
had aggressive myeloma led to lytic bone lesions, human Ig in the
serum, human plasma cells, and a high frequency of clonotypic cells in
the murine bone marrow (BM). Human B and plasma cells were detected in
BM, spleen, and blood. Injection of ex vivo multiple myeloma cells
directly into the murine sternal BM (intraosseus injection [IO])
leads to lytic bone lesions, BM plasma cells, and a high frequency of
clonotypic cells in the femoral BM. This shows that myeloma has spread
from the primary injection site to distant BM locations. By using a
cellular limiting dilution PCR assay to quantify clonotypic B lineage
cells, we confirmed that peripheral myeloma cells homed to the murine
BM after IC and IO injection. The myeloma progenitor undergoes
self-renewal in murine BM, as demonstrated by the transfer of human
myeloma to a secondary recipient mouse. For 6 of 7 patients, G-CSF
mobilized cells from patients who have minimal disease, taken at the
time of mobilization or after cryopreservation, included myeloma
progenitors as identified by engraftment of clonotypic cells and/or
lytic bone disease in mice. This indicates that myeloma progenitors are
mobilized into the blood by cyclophosphamide/G-CSF. Their ability to
generate myeloma in a xenotransplant model implies that such
progenitors are also myelomagenic when reinfused into patients, and
suggests the need for an effective strategy to purge them before transplant.
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