The increased or inappropriate expression of genes with oncogenic properties through speci®c chromosome translocations is an important event in the pathogenesis of Bcell lymphoproliferative diseases. Recent studies have found deletions or translocations of chromosome 7q to be the most common cytogenetic abnormality observed in SLVL, a leukemic variant of SMZL, with the q21 ± q22 region being most frequently a ected. In three patients with translocations between chromosomes 2 and 7, the cloning of the breakpoints at 7q21 revealed that each was located within a small region of DNA 3.6 kb upstream of the transcription start site of cyclin dependent kinase 6 (CDK6). In each case the translocation event was consistent with aberrant VJ recombination between the immunoglobulin light chain region (Ig kappa) on chromosome 2p12 and DNA sequences at 7q21, resembling the heptamer recombination site. The t(7;21) breakpoint in an additional patient with splenic marginal zone lymphoma (SMZL), resided 66 kb telomeric to the t(2;7) breakpoints juxtaposing CDK6 to an uncharacterized transcript. In two of the SLVL patient samples, the CDK6 protein was found to be markedly over expressed. These results suggest that dysregulation of CDK6 gene expression contributes to the pathogenesis of SLVL and SMZL.
It has been reported by us and by others that after chemotherapy for Hodgkin's disease the ovary contains fewer than 5 primordial and primary follicles per 5 x 5 mm biopsy section. In young women this is associated with premature menopause. We report here that before treatment the tissue contains 18--55 such follicles per biopsy section. When women took combination oral contraceptives throughout the course of MVPP therapy, the posttreatment ovarian biopsy tissue had more than 20 follicles per histologic section. Normal menses were established in the five women who discontinued oral contraceptives at the end of MVPP therapy, and one of them is now pregnant.
Cytotoxic chemotherapy has not provided survival benefit in metastatic prostate cancer, although it has been used most frequently in patients with far-advanced, refractory disease. To evaluate the effects of chemotherapy given earlier in the course of the disease, the Southwest Oncology Group (SWOG) performed a randomized trial between September 1982 and October 1986 comparing endocrine therapy (diethylstilbestrol [DES] or orchiectomy) alone followed by cyclophosphamide-Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) chemotherapy at progression versus initial combined chemo-endocrine therapy. One hundred forty-three patients were registered, and only six were declared ineligible. Patients on the combined chemo-endocrine therapy arm had a slightly higher response rate (63%) compared with endocrine therapy alone (48%). A log-linear model of tumor response and treatment arm adjusted for the stratification factors favored the combination arm (P = .059). Only three of 27 patients on the endocrine therapy alone arm had an objective partial response when crossed over to chemotherapy, while two others had stable disease. Despite the difference in initial response rate, time to treatment failure and survival were identical in the two treatment arms. Seventy-seven percent of patients on the initial endocrine therapy alone arm have died (median survival, 25.6 months) compared with 78% on the chemo-endocrine therapy arm (median survival, 22.0 months). No significant effect of treatment on survival was observed even after adjustment for the stratification variables in a Cox regression model. Exploratory survival analyses with patients on both arms combined did show a marginally significant time to treatment failure and survival advantage for patients treated with DES rather than orchiectomy as initial endocrine therapy. Eighty-six percent of patients treated by orchiectomy have died compared with only 65% of those treated with DES. These data do not support the addition of cytotoxic chemotherapy to initial endocrine therapy in patients with metastatic prostate cancer.
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