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Previous Volume 331:74-80 July 14, 1994 Number 2 Next

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ABSTRACT

Background About 40 percent of non-Hodgkin's lymphomas are diffuse lymphomas with a large-cell component (DLLC). Current therapy can induce a long-term remission in half the patients with DLLC, but more intensive treatment has the potential to improve outcome, particularly in patients at high risk for treatment failure. Clinical and cytogenetic markers can identify subgroups at high or low risk. Rearrangement of a novel candidate proto-oncogene, bcl-6, is a possible prognostic indicator in DLLC.

Methods We performed Southern blot hybridization to detect bcl-6 and bcl-2 gene rearrangement in samples of lymphoma from 102 patients with B-cell DLLC. The results were correlated with the patients' histologic features, age, disease stage, tumor sites and bulk of disease, serum lactate dehydrogenase level, and treatment outcome.

Results Rearranged bcl-6 was found in 23 cases, and rearranged bcl-2 in 21 cases. Nineteen of the patients with rearranged bcl-6 had extranodal DLLC, two had primary splenic lymphomas, and only one had bone marrow involvement. Thirty-six months after diagnosis, the proportion with freedom from progression of disease was projected to be 82 percent (95 percent confidence interval, 66 to 98 percent) among the patients with rearranged bcl-6, as compared with 56 percent (95 percent confidence interval, 43 to 70 percent) for the patients with germ-line bcl-6 and bcl-2 and 31 percent (95 percent confidence interval, 8 to 53 percent) for the patients with rearranged bcl-2. The status of the bcl-6 gene was an independent prognostic marker of survival and freedom from disease progression in a multivariate model and added predictive value to established prognostic signs.

Conclusions Rearrangement of the bcl-6 gene correlated with a favorable clinical outcome in DLLC and may thus serve as a prognostic marker in patients with this form of malignant lymphoma.

Source Information

From the Cell Biology and Genetics Program (K.O., N.Z.P., R.S.K.C.), the Departments of Medicine (K.O., C.P.), Pathology (D.C.L., D.A.F., S.J.), and Epidemiology and Biostatistics (D.L.), and the Cytogenetics Service (K.O., M.L., S.J., R.S.K.C.), Memorial Sloan-Kettering Cancer Center; and the Division of Oncology, Department of Pathology, College of Physicians and Surgeons, Columbia University (F.L.C., B.H.Y., F.L., R.D.-F.); and Columbia University (A.R.) -- all in New York; and Sezione di Ematologia, Dipartimento di Biopatologia Umana, Universita "La Sapienza" (F.L.C.), and Centro Studi e Ricerche della Sanita dell'Esercito (F.L.) -- both in Rome.

Address reprint requests to Dr. Offit at the Memorial Sloan-Kettering Cancer Center, Box 192, 1275 York Ave., New York, NY 10021.

Full Text of this Article

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The Advantage of Rearranging bcl-6
Mooi W. J., Kluin P. M., Offit K., Chaganti R.S.K.
Extract | Full Text  
N Engl J Med 1994; 331:1459-1460, Nov 24, 1994. Correspondence

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