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Human Homologue of Moloney Leukemia Virus Integration-4 Locus (MLVI-4), Located 20 Kilobases 3' of the myc Gene, Is Rearranged in Multiple Myelomas¹

Department of Medicine and Experimental Oncology, Division of Hematology, University of Torino, School of Medicine, Torino 10126, Italy [A. P. P., M. B., S. B., P. C., A. P.]; Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia 19111 [P. N. T.]; and Fels Institute for Cancer Research and Molecular Biology, Temple University, School of Medicine, Philadelphia, Pennsylvania 19140 [K. H., C. M. C.]

The structure of the c-myc locus and the flanking chromosomal region was investigated by Southern blot analysis of DNA from bone marrow aspirates from 42 patients with multiple myeloma. The main abnormality detected was the rearrangement of the MLVI-4 locus, 20 kilobases 3' of c-myc, which was observed in seven cases (16%). Two of these rearrangements were detected at the time of the initial diagnosis, four during treatment, and one at relapse, and their presence correlated with unresponsiveness to therapy. The MLVI-4 locus represents the human homologue of the Moloney leukemia virus integration-4 locus (Mlvi-4), a common region for provirus integration in Moloney murine leukemia virus-induced T-cell lymphomas in rodents. Provirus integration in this locus activates c-myc, and two additional genes, Mlvi-4 and Mlvi-1. The c-myc gene was rearranged in one patient; mutations involving the first exon of c-myc, frequently detected by altered restriction enzyme recognition sites in Burkitt's lymphomas, were not observed in these myelomas.

¹ This work was supported by a grant from the National Research Council, Special Project "Oncology", N. 88.00534.44, and from Associazione Italiana Ricerca Cancro. Also supported by NIH Grants CA21124, CA39860 and CA38047.

² To whom requests for reprints should be addressed, at Fels Institute for Cancer Research and Molecular Biology, 3420 North Broad Street, Philadelphia, PA 19140.

Received 5/14/90. Accepted 7/16/90.

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