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Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3576-3582
The Proliferative Potential of Myeloma Plasma Cells Manifest in the
SCID-hu Host
Shmuel Yaccoby and
Joshua Epstein
From the Myeloma and Transplantation Research Center, Arkansas Cancer
Research Center, University of Arkansas for Medical Sciences, Little
Rock, AR.
The low proliferative activity of myeloma plasma cells prompted the
notion that the clonotypic B cells that exist in the blood and bone
marrow of all myeloma patients contain the proliferative myeloma cells
(stem cell). We have exploited our severe combined immunodeficiency
(SCID)-hu host system for primary myeloma to investigate whether
myeloma plasma cells are capable of sustained proliferation. Purified
CD38++CD45 plasma cells consistently
grew and produced myeloma and its manifestations in SCID-hu hosts (8 of
9 experiments). In contrast, the plasma cell-depleted bone marrow cells
from 6 patients did not grow or produce myeloma in SCID-hu hosts.
Similarly, whereas plasma-cell containing blood cells from 4 patients
grew and produced myeloma in hosts, neither the
PC-depleted blood cells from 3 of the patients nor a blood
specimen that did not contain plasma cells grew in SCID-hu hosts,
regardless of their CD19-expressing cell contents. Also, in hosts
injected with blood cells, although the myeloma cells were able to
disseminate through the murine host system, they were only able to grow
in the human bones within a human microenvironment and were not
detectable in the murine blood or other organs. Interestingly, the
circulating plasma cells appear to grow more avidly in the SCID-hu
hosts than their bone marrow counterparts, suggesting that they
represent a subpopulation of the plasma cells in the bone marrow.
Although our studies clearly demonstrate the proliferative potential of
myeloma plasma cells, they are suggestive, not conclusive, as to the
existence of a preplasmacytic myeloma progenitor cell.
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