Enforced CD19 expression leads to growth inhibition and reduced tumorigenicity

In multiple myeloma (MM), the cell surface protein, CD19, is specifically l ost while it continues to be expressed on normal plasma cells. To examine t he biological significance of loss of CD19 in human myeloma, we have genera ted CD19 transfectants of a tumorigenic human myeloma cell line (KMS-5). Th e CD19 transfectants showed slower growth rate in vitro than that of contro l transfectants. They also showed a lower capability for colony formation a s evaluated by anchorage-independent growth in soft agar assay. The CD19 tr ansfectants also had reduced tumorigenicity in vivo when subcutaneously imp lanted into severe combined immunodeficiency (SCID)-human interleukin-6 (hI L-6) transgenic mice, The growth-inhibitory effect was CD19-specific and pr obably due to CD19 signaling because this effect was not observed in cells transfected with a truncated form of CD19 that lacks the cytoplasmic signal ing domain. The in vitro growth-inhibitory effect was confirmed in a nontum origenic human myeloma cell line (U-266). However, introduction of the CD19 gene into a human erythroleukemia cell line (K-562) also induced growth in hibition, 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 t o the proliferation of the malignant plasma cell clones in this disease, (C ) 1999 by The American Society of Hematology.