Biomedical subjects

Masao Seto

Publications and source records attributed to Masao Seto.

43 records · Page 3Linked to original sources

PubMed2002

De novo CD5+ diffuse large B-cell lymphoma: a clinicopathologic study of 109 patients.

De novo CD5+ diffuse large B-cell lymphoma (CD5+ DLBCL) is known to have phenotypically and genotypically different characteristics than CD5- DLBCL and mantle cell lymphoma (MCL). To further characterize CD5+ DLBCL, 109 patients with CD5+ DLBCL were reviewed, and the results were compared with those of 384 CD5- DLBCL and 128 cyclin D1+ MCL patients. Patients with CD5+ DLBCL showed a higher age distribution (median, 66 years; P =.0083) and a female predominance (male-female ratio, 49:60, P =.011) compared with those with CD5- DLBCL. CD5+ DLBCL was more closely associated with many aggressive clinical features or parameters than CD5- DLBCL: 69% older than 60 years (P =.039), 34% with performance status greater than 1 (P =.0016), 69% with serum lactate dehydrogenase level higher than normal (P <.0001), 62% with stage III/IV disease at diagnosis (P =.0023), 35% with more than one extranodal site (P =.023), and 40% with B symptoms (P =.0031). The overall International Prognostic Index score was thus significantly higher for the patients with CD5+ DLBCL than for those with CD5- DLBCL (P =.00005). The most frequent site of extranodal involvement was bone marrow (28%), a higher frequency than that for CD5- DLBCL (P <.0001) but lower than that for cyclin D1+ MCL (P =.0015). Histopathologically, CD5+ DLBCL showed centroblastic morphology except for 3 patients with immunoblastic disease, and interfollicular growth pattern (7%) and intravascular or intrasinusoidal infiltration (19%) were observed. Immunophenotypically, CD5+ DLBCL was characterized by a CD5+CD10-CD19+CD20+CD21-CD23- cyclin D1- phenotype and a predominance of surface IgMkappa. Of particular interest is that CD5+ DLBCL was characterized by a survival curve significantly inferior to that for patients with CD5- DLBCL (P =.0026). These findings suggest that CD5+ DLBCL may constitute a unique subgroup of DLBCL.

Adolescent↗

PubMed2002

Molecular cytogenetic analysis of the breakpoint region at 6q21-22 in T-cell lymphoma/leukemia cell lines.

Chromosome band 6q21 is reported to be one of the most frequent target regions in T-cell lymphoma for both translocations and deletions. To explore whether the breakpoint clustering in T-cell malignancy indicates the presence of a common breakpoint region in 6q, we employed fluorescence in situ hybridization analysis using various YAC, BAC, and PAC clones aligned at 6q21-22. We identified two T-cell lymphoma/leukemia cell lines with different differentiation stages that had breakpoints within the same novel gene, TCBA1 (T-cell lymphoma breakpoint associated target 1). In a T-cell lymphoblastic lymphoma cell line, HT-1, the TCBA1 fused to SUSP1 (SUMO-1-specific protease), creating a SUSP1-TCBA1 chimeric gene. However, in an adult T-cell leukemia cell line, ATN-1, no chimeric gene was detected, although aberrant TCBA1 transcripts were produced. We conclude that TCBA1 is a possible target gene for T-cell lineage-specific chromosome aberrations at 6q21.

Amino Acid Sequence↗

PubMed2002

Molecular mechanisms of lymphomagenesis through transcriptional disregulation by chromosome translocation.

Chromosome translation plays an important role for lymphomagenesis. Transcriptional disregulation type of chromosome translocation involves a majority of B-cell lymphoma. These include BCL1/cyclin D1 translocation in mantle cell lymphoma, BCL2 in follicular lymphoma and BCL6 in diffuse large B-cell lymphoma. It is known that the transcriptional disregulation type causes aberrant gene expression at the stages where those genes are down-regulated in normal counterpart cells. Normal B-cells at mantle zone stage down-regulate the expression of BCL1 gene and become resting in cell cycle. However, BCL1 expression from translocated allele with immunoglobulin gene is not down-regulated at the mantle zone stage, preventing cells from entering in resting state, and puts cells in cell cycle, leading to development of mantle cell lymphoma. BCL2 expression from altered allele also keeps its expression at the germinal center stage where normal counterpart cells down-regulate BCL2 expression, and makes cells to resist apoptosis, leading to development of follicular lymphoma. The same scenario can apply to diffuse large B-cell lymphoma with BCL6 translocation; i.e. aberrant BCL6 expression at the post germinal center stage takes place where normal counterpart cells down-regulate BCL6 expression. Although a strong association of specific translocations with specific disease types is found, these translocations by themselves are not sufficient for malignant transformation. The factors other than chromosome translocations will be discussed.

Gene Expression Regulation, Neoplastic↗

PubMed2002

Fuzzy neural network applied to gene expression profiling for predicting the prognosis of diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the largest category of aggressive lymphomas. Less than 50% of patients can be cured by combination chemotherapy. Microarray technologies have recently shown that the response to chemotherapy reflects the molecular heterogeneity in DLBCL. On the basis of published microarray data, we attempted to develop a long-overdue method for the precise and simple prediction of survival of DLBCL patients. We developed a fuzzy neural network (FNN) model to analyze gene expression profiling data for DLBCL. From data on 5857 genes, this model identified four genes (CD10, AA807551, AA805611 and IRF-4) that could be used to predict prognosis with 93% accuracy. FNNs are powerful tools for extracting significant biological markers affecting prognosis, and are applicable to various kinds of expression profiling data for any malignancy.

DNA-Binding Proteins↗

PubMed2002

Clinicopathologic comparison between the API2-MALT1 chimeric transcript-positive and -negative gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type.

Little is known about the clinicopathological differences between API2-MALT1 chimeric transcript-positive and -negative gastric low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type. The aim of this study was to clarify those differences in gastric MALT lymphoma. Twenty-three patients with gastric MALT lymphoma were enrolled in a unicenter study. Helicobacter pylori (H. pylori) infection status and clinical stages were investigated. Antibacterial treatment was performed for every patient. Responsiveness of MALT lymphoma to this treatment was assessed by means of regular follow-up endoscopy combined with biopsy. All cases were examined for API2-MALT1 chimeric transcript by means of RT-PCR and sequencing analyses. H. pylori infection status was assessed as positive in 20 patients and negative in three. With regard to responsiveness to antibacterial treatment, complete remission was observed in two patients, partial remission in 12 and no change in nine. API2-MALT1 chimeric transcript was detected in seven patients, all of whom showed no change in response to antibacterial treatment. API2-MALT1 positivity was found to be significantly correlated with responsiveness to antibacterial treatment (P = 0.0001), absence of H. pylori infection (P = 0.0198), and gross cobblestone mucosa observed endoscopically (P = 0.0198). For the other factors (age, sex, dominant site of lesion, high-grade component, infiltrated layer of gastric wall, nodal involvement or clinical stages), there were no differences between API2-MALT1 chimeric transcript-positive and -negative cases. Gastric API2-MALT1 chimeric transcript-positive MALT lymphoma generally features unresponsiveness to antibacterial treatment, and is thought to be unrelated to H. pylori infection in its pathogenesis. Our findings indicate the presence of different clinical subtypes in gastric MALT lymphomas.

Adult↗

PubMed2002

MUM1/IRF4 expression is an unfavorable prognostic factor in B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

B-Cell chronic lymphocytic leukemia (B-CLL) / small lymphocytic lymphoma (SLL) consists of heterogeneous diseases that are distinguished by morphological, immunophenotypic and molecular features. MUM1 (multiple myeloma oncogene 1) is a protooncogene that is deregulated as a result of (6;14)(p25;q32) chromosomal translocation in multiple myeloma, and is also expressed in a variety of malignant lymphoma entities. We examined the expression of MUM1 in B-CLL / SLL, and found that 2 of 4 B-CLL-derived cell lines and 14 of 29 patients' specimens expressed MUM1 by immunohistochemical analysis. MUM1 expression was not associated with CD38 expression, somatic hypermutation of immunoglobulin heavy chain gene variable region (IgV(H)), or any other clinical characteristics of the patients. Interestingly, the patients who were positive for MUM1 showed shorter overall survival times than those who were negative for MUM1 (50% survival: 22 months vs. 82 months) (P = 0.0008, log-rank test). Multivariate analysis by Cox's proportional-hazards regression model showed that MUM1 expression and unmutated IgV(H) status were independent unfavorable prognostic factors in patients with B-CLL / SLL. These findings suggest that MUM1 expression is a useful prognostic factor in B-CLL / SLL. The biological role and mechanism of action of MUM1 in B-CLL / SLL need to be clarified for the development of therapies for patients with the poor prognostic subtype.

ADP-ribosyl Cyclase↗

PubMedDate not supplied

Mutational analysis of the ST7 gene in human myeloid tumor cell lines.

The recently described ST7 (for suppression of tumorigenicity 7) gene has been suggested to be a major target gene on chromosome 7q31 for inactivation in a variety of human neoplasias. Loss of heterozygosity (LOH) in chromosome 7q31 is frequently observed in a variety of human neoplasias including malignant myeloid tumors. We, therefore, sought to examine a total of 22 human malignant myeloid tumor cell lines comprising 17 of acute myelogenous leukemia (AML) cell lines and 5 chronic myelogenous leukemia (CML) cell lines for somatic mutations of the ST7 gene by means of bidirectional direct DNA sequencing analysis. As a result, no mutations were detected in any of these cell lines examined. In addition, our analysis of two breast tumor cell lines, which had been reported to harbour ST7 mutations, provided no evidence for such mutations. Thus, our results strongly suggest that somatic mutations of ST7 do not commonly contribute to the molecular pathogenesis of human malignant myeloid tumors and further raise questions regarding the pathological role of ST7 as a tumor suppressor gene (TSG) in a variety of human neoplasias.

Base Sequence↗