Immunoglobulin (Ig)/BCL6 versus non-Ig/BCL6 gene fusion in diffuse large B-cell lymphoma corresponds to a high- versus low-level expression of BCL6 mRNA.
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Artificial Gene Fusion↗
Biomedical subjects
Hitoshi Ohno
Publications and source records attributed to Hitoshi Ohno.
The gene for interleukin-21 receptor is the partner of BCL6 in t(3;16)(q27;p11), which is recurrently observed in diffuse large B-cell lymphoma.
BCL6 translocation affecting the chromosomal band 3q27 can involve a number of non-immunoglobulin (non-IG) gene loci as partners. We report here that the gene for interleukin-21 receptor (IL-21R) is the partner of BCL6 in t(3;16)(q27;p11) translocation. The two breakpoints on 16p11 of a lymphoma cell line YM and case no. 1012 with diffuse large B-cell lymphoma, both of which carried t(3;16), were localized within the 27-kb intron 1 of IL-21R. As a result of t(3;16), the promoter region of IL-21R was substituted for the regulatory sequences of BCL6 in the same transcriptional orientation. Reverse transcriptase-mediated polymerase chain reaction revealed chimeric mRNA consisting of two non-coding exons 1a/1b of IL-21R and coding exons of BCL6 in both lymphoma cells. Fluorescence in situ chromosomal hybridization of YM metaphase cells revealed fusion signals that contained both the BCL6 and IL-21R sequences on the der(3)t(3;16) chromosome. IL-21R was actively transcribed in YM cells, while BCL6 that was under the control of the IL-21R promoter was only moderately expressed at the mRNA and protein level. We constructed expression plasmid of BCL6 that followed the promoter sequences of IL-21R. COS-7 cells transiently transfected with the plasmid expressed high level Bcl-6 protein and displayed nuclear staining with a characteristic punctate pattern by immunofluorescence, indicating that expression of BCL6 can be enhanced by t(3;16). This study added to the list of non-IG partners of BCL6 translocations a new class of gene, i.e. cytokine receptor gene, the expression of which is closely associated with lymphoid cells.
Animals↗
Predictors of lower pole renal stone clearance after extracorporeal shock wave lithotripsy.
PURPOSE: Lower pole renal stones are well known to show a poor stone clearance rate after extracorporeal shock wave lithotripsy (ESWL) (Dornier Medical Systems, Marietta, Georgia). In the current study we analyzed several anatomical factors as predictors of lower pole stone clearance that may be used to indicate the usefulness of ESWL in such patients. MATERIALS AND METHODS: Between January 1993 and October 2000, 63 patients with a unilateral single lower pole stone of 2 cm. or less were included in the study. Excretory urography was done to determine the lower infundibulopelvic angle, caliceal pelvic height, lower infundibular length and diameter, lower infundibular length-to-diameter ratio and number of lower pole minor calices. Stone-free status was assessed by x-ray. RESULTS: The overall stone clearance rate was 54% (34 of 63 patients). While caliceal pelvic height, lower infundibular diameter, length, length-to-diameter ratio and number of minor calices were different in the stone-free and residual stone groups on univariate analysis, multivariate logistic analysis revealed that the lower infundibular length-to-diameter ratio, diameter and number of minor calices were independent predictors of successful stone clearance. The 13 patients (20.6%) who showed all 3 favorable anatomical factors (lower infundibular length-to-diameter ratio less than 7, diameter greater than 4 mm. and a single minor calix) achieved an impressive 84.6% stone clearance rate. In patients with only 1 or 2 favorable factors the stone clearance rate was still greater than 60%. In contrast, the stone clearance rate was only 6.7% in the 15 patients who showed none of these factors. CONCLUSIONS: From this study it is apparent that successful ESWL is highly sensitive to the anatomy of the lower pole of the kidney. If a patient with a lower pole stone has at least 1 of the favorable factors identified in this study, ESWL may be advocated as first line therapy with a greater than 60% prospect of a successful outcome. Other treatment options should be considered in those without any of these predictive factors.
Adult↗
Non-immunoglobulin/BCL6 gene fusion in diffuse large B-cell lymphoma: prognostic implications.
3q27 translocation affecting the BCL6 gene is one of the most common chromosomal abnormalities in diffuse large B-cell lymphoma (DLBCL). BCL6 translocation can involve not only one of the three immunoglobulin gene (Ig) loci but also another non-Ig chromosomal locus. 5'-rapid amplification of cDNA ends and long-distance inverse polymerase chain reaction (PCR) methods have identified a total of 13 recurrent non-Ig partner genes to date. As the result of non-Ig/BCL6 translocation, many types of regulatory sequences of each partner gene substitute for the 5' untranslated region of the BCL6 and the rearranged BCL6 is presumed to be under the control of the replaced promoter activity. BCL6 translocation occurs more frequently in extranodal DLBCL than in node-based disease. However, the impact of BCL6 translocation on the treatment outcome of DLBCL has been the subject of controversy. We found that survival of DLBCL patients with non-Ig partners was inferior to that of those with Ig/BCL6 translocation, suggesting that non-Ig/BCL6 fusion is a poor prognostic indicator of DLBCL. We next created BCL6 expression plasmids containing a series of non-Ig/BCL6 fusion genes. COS-7 cells transiently transfected with these plasmids expressed high levels of Bcl-6 protein and showed characteristic punctate nuclear staining. These findings suggested that non-Ig/BCL6 translocation plays a pathogenetic role in a proportion of DLBCL.
Breast Neoplasms↗
Clinical characteristics of alpha-blocker responders in men with benign prostatic hyperplasia.
BACKGROUND: Currently, alpha-blocker is becoming first-line drug therapy for benign prostatic hyperplasia (BPH). Although highly effective results are obtained with this therapy, a difference between the objective and subjective response rates is reported. To prevent unnecessary medical treatment and to predict the alpha-blocker response, we characterized the clinical features of alpha-blocker responders in men with BPH. METHODS: Twenty-two men were consecutively enrolled in this study and received tamsulosin 0.2 mg once daily for 4-6 weeks. The primary measures of efficacy were maximum urinary flow rate (Q(max)) determined from the flow measurements and international prostate symptom score (IPSS). Those with an increase in Q(max) of > or = 30% from baseline and a decrease in IPSS of > or = 25% from baseline were defined as Q(max) responders and IPSS responders, respectively. Clinical findings such as age, pretreatment IPSS and Q(max), serum prostate-specific antigen (PSA), total prostate volume, transition zone (TZ) volume, TZ index and T(2)-weighted magnetic resonance image (MRI) of the prostate TZ were compared between responders and non-responders for both criteria. RESULTS: In 17 of 22 (77.2%) patients IPSS improved by > or = 25%. In 9 of 22 (40.9%) patients Q(max) improved by > or = 30%. There were no differences in clinical findings between IPSS responders and non-responders. On the contrary, Q(max) responders showed smaller total prostate and TZ volumes, a smaller TZ index and a lower intensity of the TZ in MRI than Q(max) non-responders. CONCLUSIONS: Determination of the prostate volume and MRI findings of the inner prostate gland were useful in predicting Q(max) responders to the alpha-blocker in men with BPH. In contrast, there were no clinical characteristics of the IPSS responders. IPSS responders without a Q(max) response should be closely followed while continuing the alpha-blocker therapy for a long duration.
Adrenergic alpha-Antagonists↗
Cerebral atherosclerosis and coronary calcification.
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Age Distribution↗
[Significance of soluble interleukin-2 receptor alpha chain in the management of patients with malignant lymphoma: a multi-center study].
A multi-center series of 117 patients with malignant lymphoma were analyzed to evaluate the clinical significance of soluble interleukin-2 receptor alpha chain (sIL-2R alpha). The initial levels of sIL-2R alpha ranged from 277 U/ml to 22,800 U/ml with a mean level of 3,451 +/- 4,268 U/ml and a median level of 1,600 U/ml. The sIL-2R alpha levels of the diffuse lymphoma/intermediate-grade subtypes defined by the LSG classification/Working Formulation were higher than those of the follicular lymphoma/low-grade subtypes. There was a tendency for B-cell lymphomas to show higher sIL-2R alpha levels than T-cell lymphomas. The sIL-2R alpha level was correlated with the Ann Arbor clinical stage (I, II versus III, IV), presence or absence of B symptoms, and performance status (0, 1 versus 2, 3, 4) of the patients. The sIL-2R alpha levels were in good accordance with the four risk groups defined by the International Prognostic Indices. Of 21 patients whose tumor burden was serially measured, the coefficients of correlation between sIL-2R alpha and tumor mass were > 0.6 in 18 cases. Sixty-two patients achieved complete remission (CR) during the study; the initial and minimum sIL-2R alpha levels were lower than those of the non-CR patients. This study confirmed that sIL-2R alpha is a convenient and useful marker in the management of malignant lymphoma.
Female↗