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Antiimmunoglobulin Inhibition of Burkitt's Lymphoma Cell Proliferation and Concurrent Reduction of c-myc and µ Heavy Chain Gene Expression

Pediatric Oncology Branch, and Navy Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892 [V. E. A., J. S., J. K., L. N., I. K., G. H., I. T. M.]; and Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20857 [R.L.]

We have demonstrated that polyvalent antiimmunoglobulin antibodies directed at appropriate cell surface light (L) or heavy (H) immunoglobulin (Ig) chains will inhibit proliferation and the expression of c-myc and µ-Ig chain mRNA in Burkitt's lymphoma (BL) cell lines bearing 8;14 chromosomal translocations. This effect was not observed in BL cell lines bearing 8;22 translocations or in BL cell lines which did not express surface Ig or in karyotypically normal Epstein-Barr virus-transformed lymphoblastoid cell lines. The antiproliferative effect was reproducible and resulted in cell death in the most sensitive cell lines. The decrease in gene expression preceded the antiproliferative effect. The effect of anti-Ig on gene expression was relatively specific since the level of total (shown by Northern blots) and cytoplasmic (dot blots) mRNA of several other genes (ß-actin, G6PD, -L chain) and the first exon of c-myc (in cell lines in which this exon is expressed separately from the second and third exons) was not changed in these same BL cell lines. Expression of both c-myc and µ was maximally inhibited between 3 and 6 h after the addition of anti-Ig. In the most sensitive BL cell line, concurrent reduction in c-myc and µ mRNA was noted as early as 1 h after anti-Ig and the nadir of expression of these genes occurred at 3 h. These results indicate that the deregulated high constitutive expression of c-myc in some BLs can be down-regulated by anti-Ig resulting in inhibition of proliferation and cell death. In addition these data are consistent with the possibility that in at least some 8;14 bearing BLs the malignant transformation occurs in an immature B-cell undergoing antigen-independent differentiation.

¹ Present address: Department of Pediatric Hematology and Oncology, St. Judes Children's Research Hospital, Memphis, TN.

² Present address: Department of Pediatrics, Rainbow Babies and Children's Hospital, Cleveland, OH.

³ Present address: Monsanto Corp., St. Louis, MO.

⁴ To whom requests for reprints should be addressed, at Pediatric Oncology Branch, Building 10, Room 13N240, National Cancer Institute, NIH, Bethesda, MD 20892.

Received 9/15/88. Revised 1/30/89. Accepted 3/ 3/89.

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