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Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3551-3558
Enforced CD19 Expression Leads to Growth Inhibition and Reduced
Tumorigenicity
Maged S. Mahmoud,
Ryuichi Fujii,
Hideaki Ishikawa, and
Michio M. Kawano
From the Department of Immunohematology, Yamaguchi University School
of Medicine, Ube, Japan.
In multiple myeloma (MM), the cell surface protein, CD19, is
specifically lost while it continues to be expressed on normal plasma
cells. To examine the biological significance of loss of CD19 in human
myeloma, we have generated CD19 transfectants of a tumorigenic human
myeloma cell line (KMS-5). The CD19 transfectants showed slower growth
rate in vitro than that of control transfectants. They also showed a
lower capability for colony formation as evaluated by
anchorage-independent growth in soft agar assay. The CD19 transfectants also had reduced tumorigenicity in vivo when subcutaneously implanted into severe combined immunodeficiency (SCID)-human interleukin-6 (hIL-6) transgenic mice. The growth-inhibitory effect was
CD19-specific and probably due to CD19 signaling because this effect
was not observed in cells transfected with a truncated form of CD19
that lacks the cytoplasmic signaling domain. The in vitro
growth-inhibitory effect was confirmed in a nontumorigenic human
myeloma cell line (U-266). However, introduction of the CD19 gene into
a human erythroleukemia cell line (K-562) also induced growth
inhibition, suggesting that this effect is CD19-specific, but not
restricted to myeloma cells. These data suggest that the specific and
generalized loss of CD19 in human myeloma cells could be an important
factor contributing to the proliferation of the malignant plasma cell
clones in this disease.
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