Biomedical subjects

M Seto

Publications and source records attributed to M Seto.

At least 91 records · Page 5Linked to original sources

PubMed1999

Selective usage of D-type cyclins in lymphoid malignancies.

Three D-type cyclins, cyclin D1, D2 and D3, belong to the G1 cyclin, which regulates the G1/S transition of the cell cycle, and feature highly homologous amino acid sequences. The cyclin D1 gene was found to be transcriptionally activated in B-lymphoid malignancies with t(11;14), but available information is limited regarding expression of cyclin D2 and D3 in hematopoietic malignancies. We examined the expressions of three D-type cyclins to investigate how these homologous genes are differentially used. Northern blot hybridization with densitometric analyses was performed to examine 64 cell lines and 159 patients with various hematopoietic malignancies. Among lymphoid malignancies, cyclin D1 overexpression was exclusively detected in B cell malignancies accompanied by a genetic event consisting of 11q13 chromosomal translocation, consisting of 13 of 19 (68%) patients with mantle cell lymphoma, two of 11 (18%) with B-chronic lymphocytic leukemia, and one of six (17%) with multiple myeloma. The cyclin D2 expression was significantly higher in T cell malignancies than in B cell malignancies (P = 0.003 for cell lines and P < 0.0001 for patient samples, respectively). In the T cell malignancies, cyclin D2 overexpression was predominantly recognized in those with mature phenotype. Furthermore, cyclin D2 expression was upregulated by phytohemagglutinin (PHA) stimulation of normal T-lymphocytes, suggesting that this simply represents the proliferation status of mature T cells. Although cyclin D3 was ubiquitously expressed, its expression was reduced in lymphoid malignancies with cyclin D1 or D2 overexpression. In myeloid leukemias, although three D-type type cyclins were differentially expressed, no preference for particular D-type cyclins was found. This selective usage of D-type cyclins in lymphoid malignancies suggests an existence of a regulatory mechanism among three D-type cyclins.

Cell Lineage↗

PubMed1999

Molecular and immunological dissection of diffuse large B cell lymphoma: CD5+, and CD5- with CD10+ groups may constitute clinically relevant subtypes.

Diffuse large B cell lymphoma (DLBL) constitutes the greatest percentage of adult non-Hodgkin's lymphomas and represents a diverse spectrum of lymphoid neoplasms. Clinicopathologic, phenotypic and genotypic findings were correlated and compared for 63 DLBL cases to investigate whether they represent clinically relevant subtypes. They were all cyclin D1 negative and were phenotypically divided into three groups, ie group I (CD5+ type, n=11), group II (CD5- CD10+ type, n=19), and group III (CD5- CD10- type, n=33). Data were correlated by observing the respective gene rearrangement and expression of BCL2 and BCL6. In clinical aspects, the group I cases demonstrated a significantly inferior survival than those of the other two groups (log-rank test, P = 0.016). Although rearrangement of BCL2 and BCL6 did not show any inclination to a specific subgroup, the immunohistochemical detection of BCL2 was less frequent, at a statistically significant level (P=0.011), in group II (50%) than in group I (82%) and III (82%) cases. This appears to confirm the unique aspect of the CD5- CD10+ type DLBL, indicating a certain relationship with the normal germinal center cells which usually lack BCL2 expression. The BCL6 protein expression was detected in most of the present DLBL cases (92%) irrespective of this grouping. These data suggest that the phenotypic delineation by the detection of CD5 and CD10 will improve our understanding of DLBL and be helpful in a future subgrouping of DLBL.

Adult↗

PubMed1999

Primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma with polypoid appearance. Polypoid gastric MALT lymphoma: A clinicopathologic study of eight cases.

In the current study, we report eight cases with primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma endoscopically characterized by polypoid lesions in order to highlight their clinicopathologic significance. Four patients were male, their ages ranging from 40 to 78 years old. The resected specimens revealed a histology of low-grade MALT lymphoma characterized by dense lymphocytic infiltration predominantly in the submucosa and a relatively monotonous proliferation of centrocyte-like cells with reactive follicles and infrequent lymphoepithelial lesions. The tumor cells were of CD5-, CD10-, CD20+, BCL2+ and cycline D1- phenotype, and showed a monoclonal rearrangement of immunoglobulin heavy chain genes in the five of six cases examined. Interestingly, Helicobacter pylori (H. pylori) was detected in three (37.5%) of the eight patients, which was significantly lower than previous reports. Two of the H. pylori-positive cases initially underwent H. pylori eradication, but showed no change in their lymphomas after the cure of H. pylori infection. The clinicopathologic findings of the present cases appeared to closely resemble those of colorectal MALT lymphoma with a polypoid appearance and few association of H. pylori infection in their pathogenesis. These gastric polypoid cases may merit separate consideration because of the therapeutic problems they pose.

Adult↗

PubMed1999

Hodgkin's disease expressing follicular dendritic cell marker CD21 without any other B-cell marker: a clinicopathologic study of nine cases.

Reed-Sternberg (RS) and Hodgkin's (H) cells are considered to be the neoplastic cells in Hodgkin's disease (HD). Although most data suggest their lymphoid origin, the nature of these cells still remains a subject of controversy. Recently, a number of RS cells have been found to express an antigen that is also present on follicular dendritic cells (FDCs), asserting FDCs as the possible progenitor cells of H-RS cells. This prompted us to investigate whether these CD21-positive cases had distinct clinicopathologic characteristics. In a series of 94 examined cases of HD, we identified 9 CD21-positive ones (4 of 37 cases of nodular sclerosis, 1 of 41 mixed cellularity, and 4 of 12 lymphocyte depletion HD) without any other B-cell marker on paraffin sections. The patients varied in age from 16 to 82 years (median, 50 years) and included six men and three women. They had superficial or mesenteric lymphadenopathy without hepatosplenomegaly. Peripheral blood leukocytosis was seen in three patients. The clinical course was indolent, and all patients but one achieved an initial complete response with HD-based treatment regimens, although three of them relapsed. Morphologically, two subgroups could be delineated. Six of the cases were characterized, besides by the classic RS cells, by a varying number of the cells with the distinctive walnutlike or cerebrumlike nuclei and cytologically with cytoplasmic processes. Their fine structural examination also revealed villous processes, but no desmosomes. The other three cases had multinucleated RS cells often with triangular nuclei, but not cytoplasmic processes. The percentage of CD21-positive tumor cells ranged from less than 10% to 60% among the H-RS cells. These RS cells were positive for CD30 (9 of 9), CD15 (7 of 9), CD68 (1 of 8), fascin (8 of 8), S-100 protein (1 of 7), and epithelial membrane antigen (2 of 8) on paraffin sections. Notably, of eight cases examined on frozen sections, two showed immunostaining for DRC1, CD35, R4/23, and Ki-M4p. Only CD35 was also detected in the other two cases. Genotypic investigation showed germline configuration of the T-cell receptor beta and gamma chain genes and the immunoglobulin heavy chain gene in all eight cases examined. In situ hybridization showed Epstein-Barr virus sequences in four cases, three of which were examined by the terminal region analysis and showed the Epstein-Barr virus to be monoclonal. We concluded that in a small proportion (9.6%) of HD, H-RS cells might be derived from FDCs and that they appear to represent a distinct pathologic variant based on morphologic and phenotypic traits within the framework of HD.

Adolescent↗

PubMed1999

Nodal cytotoxic lymphoma spectrum: a clinicopathologic study of 66 patients.

The expression of cytotoxic granule-associated proteins has been reported in some T-cell or natural killer (NK)-cell lymphomas of mostly extranodal origin, but rarely of nodal origin except for anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD). This study analyzed 66 nodal lymphomas expressing T-cell intracellular antigen-1 (TIA-1) and/or granzyme B to characterize the clinicopathologic spectrum of these neoplasms. Four main groups could be delineated. The first group consisted of p80/anaplastic lymphoma kinase (ALK)-positive ALCL (n = 35). The patients were 2 to 62 years of age (median age, 16 years), and the lymphomas pursued a relatively indolent clinical course. The tumors were phenotypically of either T- or null-cell type with constant expression of CD30, epithelial membrane antigen (EMA), and p80/ALK, but not CD15 or BCL2. None harbored Epstein-Barr virus (EBV). The second group consisted of peripheral T/NK-cell lymphoma, the nodal high-grade cytotoxic type (n = 13). The patients were 29 to 72 years in age (median age, 55 years), and the tumors pursued an aggressive clinical course. The tumors often showed pleomorphic, anaplastic, or centroblastoid morphology, and were featured by either EBV association or CD56 expression. The third group consisted of peripheral T-cell lymphoma, of the nodal low-grade cytotoxic type (n = 8). The patients, three men and five women, were 31 to 75 years old (median age, 61 years). Notably, six of them exhibited lymphoepithelioid (Lennert's) lymphoma. The fourth group consisted of cytotoxic Hodgkin's-like ALCL/HD (n = 10), included seven cases of Hodgkin's-like ALCL and three cases of HD, and was characterized by the presence of Reed-Sternberg cells and often the CD15+ phenotype. The patients were all men except for one woman, and they ranged in age from 24 to 84 years (median age, 62 years). The link among these four groups was reinforced by the presence of a highly characteristic large cell with horseshoelike or reniform nuclei-the frequent expression of CD30 and EMA-and the often lack of T-cell receptor-alphabeta. In this series, the expression of p80/ALK and CD56 was also associated with favorable and poor prognoses respectively (p<0.001, log-rank test).

Adolescent↗

PubMed1999

Comparison of computed tomography and pathologic examination for evaluation of response of primary lung cancer to neoadjuvant therapy.

Twenty-four patients (nine with squamous cell carcinoma, 14 with adenocarcinoma, and one with large cell carcinoma) underwent neoadjuvant therapy followed by surgical resection. The authors studied changes in tumor size, shape, and contrast enhancement on computed tomography (CT), and compared them with results of pathologic examination of surgical specimens. The size of tumors on CT was evaluated according to the criteria of the World Health Organization. Surgical specimens were evaluated histologically on the basis of the area of viable cancer cells. Of 14 patients considered to have a partial response on the basis of World Health Organization criteria, five had pathologic changes of complete response. After therapy, the residual tumors in these five patients showed irregular shapes with concave tumor margins on CT images and no enhancement. The authors found that CT size criteria tended to underestimate the therapeutic effect demonstrated by pathologic examination. On the basis of these results, the authors propose three CT criteria for complete response: 1) more than 50% size reduction, 2) a change in tumor morphologic features from round or oval to irregular after neoadjuvant therapy, and 3) disappearance of contrast enhancement.

Adenocarcinoma↗

PubMed1999

Crystallographic analysis of potent and selective factor Xa inhibitors complexed to bovine trypsin.

Factor Xa is a serine protease which activates thrombin (factor IIa) and plays a key regulatory role in the blood-coagulation cascade. Factor Xa is, therefore, an important target for the design of anti-thrombotics. Both factor Xa and thrombin share sequence and structural homology with trypsin. As part of a factor Xa inhibitor-design program, a number of factor Xa inhibitors were crystallographically studied complexed to bovine trypsin. The structures of one diaryl benzimidazole, one diaryl carbazole and three diaryloxypyridines are described. All five compounds bind to trypsin in an extended conformation, with an amidinoaryl group in the S1 pocket and a second basic/hydrophobic moiety bound in the S4 pocket. These binding modes all bear a resemblance to the reported binding mode of DX-9065a in bovine trypsin and human factor Xa.

Animals↗

PubMed1999

Infrequent BCL10 mutations in B-cell non-Hodgkin's lymphomas.

The BCL10 gene was recently isolated from the breakpoint region of t(1;14)(p22;q32) in mucosa-associated lymphoid tissue (MALT) lymphomas. Somatic mutations of BCL10 were found in not only t(1;14)-bearing MALT lymphomas, but also a wide range of other tumors. To clarify the actual frequency and spectrum of BCL10 mutations in primary B-cell non-Hodgkin's lymphomas (NHL), we examined a total of 139 NHL cases comprising 25 with MALT lymphomas, 54 with follicular B-cell lymphomas (FCL), and 60 with diffuse large B-cell lymphomas (DLBL). Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and sequencing analyses led to the identification of four nucleotide changes in FCL and one in DLBL. In contrast, no BCL10 mutations were found in our series of MALT lymphomas. While screening for mutations, we also found three polymorphic sequence variants at codons 5 and 213 and in intron 1 of the BCL10 gene. Our results strongly suggest that somatic mutations of BCL10, if they occur at all, are rare in B-cell NHLs and do not commonly contribute to their molecular pathogenesis.

Adaptor Proteins, Signal Transducing↗

PubMed1999

[The molecular mechanism of vasospasm and the attenuation by fasudil].

Increase in cytosolic Ca2+ concentration and phosphorylation of myosin light chain (MLC) are key steps of normal and abnormal contractility in smooth muscle. In pathological condition like vasospasm, artery exhibits a hyperreactive contraction associated with an enhanced and sustained MLC phosphorylation, particularly diphosphorylation (Thr18/Ser19). Phosphorylation levelis regulated by a balance between phosphorylation and dephosphorylation. Recent studies propose that myosin phosphatase activity is regulated through the phosphorylation of 130K-myosin binding subunit (MBS130K) of the myosin phosphatase in smooth muscle. It is known that in normar artery, receptor agonists like PGF2 alpha induce certain contraction of smooth muscle associated with MLC diphosphorylation. We recently confirm that this PGF2 alpha stimulation also evokes the phosphorylation of MBS130K and fasudil, Rho-kinase inhibitor, inhibits this phosphorylation in parallel with MLC phosphorylation. Furthermore, we reveal that in vasospastic artery, Rho-kinase activity is augmented to induce high level phosphorylation of MBS130K. In this study, we also confirm that phosphorylation of MBS130K is Rho-kinase-dependent and its site is Thr654 residue. Now we speculate that fasudil may shift the phosphorylation-dephosphorylation cycle to dephosphorylation side through the inhibition of Thr654phosphorylation in MBS130K. These results also suggest that augmented activation of Rho-kinase may be involved in the pathophysiology of vasospasm associated with MLC diphosphorylation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1999

Ground-glass opacity on thin-section CT: value in differentiating subtypes of adenocarcinoma of the lung.

OBJECTIVE: The purpose of this study was to determine whether thin-section CT could be used to differentiate small localized bronchioloalveolar carcinoma from peripheral adenocarcinoma having a bronchioloalveolar (replacement) growth pattern of alveolar lining cells and from adenocarcinoma not having a replacement growth pattern on the basis of the extent of ground-glass opacity revealed by thin-section CT. MATERIALS AND METHODS: One hundred twenty-four small, surgically resected, peripheral adenocarcinomas from 119 patients (67 men and 52 women; mean age, 60 years) were studied. Lesion diameters were 0.4-2.0 cm (median, 1.5 cm). The extent of ground-glass opacity within lesions on preoperative thin-section CT was reviewed retrospectively by three thoracic radiologists. On the basis of replacement growth of alveolar lining cells, small adenocarcinomas were classified histologically as localized bronchioloalveolar carcinomas (n = 42) or as adenocarcinomas with (n = 53) or without (n = 29) a replacement growth pattern of alveolar lining cells. RESULTS: The percentage of lesions that had ground-glass opacity was significantly greater in localized bronchioloalveolar carcinomas (mean, 56.7%+/-33.0%) than in adenocarcinomas with a replacement growth pattern (mean, 26.3%+/-25.3%, p < .001) or in adenocarcinomas without a replacement growth pattern (mean, 8.3%+/-4.7%, p < .001). CONCLUSION: Determination of the ground-glass opacity area in each tumor as revealed on thin-section CT was useful for differentiating small localized bronchioloalveolar carcinomas from small adenocarcinomas not having a replacement growth pattern.

Adenocarcinoma↗

PubMed1999

Gene therapy of chondrosarcoma using retrovirus vectors encoding the herpes simplex virus thymidine kinase gene.

Human chondrosarcoma cells (HCS-TG) were transduced with the gene for a herpes simplex virus thymidine kinase (HSV-tk) or Escherichia coli beta-galactosidase (lacZ). We investigated the cytotoxicity of human chondrosarcoma bearing an HSV-tk gene after treatment with ganciclovir. Chondrosarcoma cells bearing an HSV-tk gene were more sensitive than non-transduced cells. Coculturing with chondrosarcoma cells bearing both an HSV-tk gene (HCS-TG-tk) and lacZ gene (HCS-TG-Z) in various ratios showed a bystander effect. Chondrosarcoma implanted in nude mice were injected with HCS-TG-tk cells. After 4 weeks, the growth of tumors was significantly prevented.

Animals↗

PubMed1999

Loss of 123I-MIBG uptake by the heart in Parkinson's disease: assessment of cardiac sympathetic denervation and diagnostic value.

UNLABELLED: Myocardial imaging with 123I-metaiodobenzylguanidine (MIBG) was performed on 35 patients with Parkinson's disease and 24 control subjects to evaluate cardiac sympathetic function in patients with Parkinson's disease, verify this phenomenon and examine whether myocardial MIBG uptake and clearance are correlated with the clinical severity of Parkinson's disease. METHODS: We studied 35 patients with Parkinson's disease and 24 control subjects with other central nervous system diseases. The latter group consisted of 12 subjects with other neurodegenerative disorders (4 with spinocerebellar degeneration, 2 with amyotrophic lateral sclerosis, 3 with progressive supranuclear palsy and 3 with corticobasal degeneration and 12 patients with cerebral infarction (CI), 6 with vascular parkinsonism and 6 without it. Early and delayed images of the anterior view were obtained 15 min and 4 h after injection of 123I-MIBG, respectively. MIBG uptake was quantified by calculating a heart-to-mediastinum count (H/M) ratio. RESULTS: The H/M ratio was markedly reduced in the patients with Parkinson's disease (II to V on the Hoehn and Yahr scale) compared with the control subjects. None of the subjects with neurodegenerative diseases showed a marked decrease in myocardial MIBG uptake nor did any subject with CI. CONCLUSION: Our findings indicate that, in Parkinson's disease, a reduction in myocardial MIBG uptake is a very common, specific phenomenon that can be used to detect cardiac autonomic dysfunction to diagnose Parkinson's disease, particularly in patients without typical signs and symptoms.

3-Iodobenzylguanidine↗

PubMed1999

Molecular cytogenetic delineation of the breakpoint at 18q21.1 in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue.

Extranodal malignant non-Hodgkin lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma) represents a subtype of B-cell lymphoid malignancies with distinct clinicopathological features and is often associated with a favorable prognosis. Recent cytogenetic studies have revealed that t(11;18)(q21;q21) is a characteristic chromosomal aberration in low-grade B-cell MALT-type lymphoma. In the present study, we employed florescence in situ hybridization analysis using contiguous YAC clones mapped to the 18q21.1 region to identify a YAC clone, y789F3, encompassing the breakpoint of t(11;18)(q21;q21) in a MALT lymphoma. PI artificial chromosome (PAC) contigs constructed on this YAC clone were used to analyze the breakpoint region. PAC clone 264m4 was observed on normal chromosome 18 and on der(18), and PAC clone 879n 10 on normal chromosome 18 and on der(II), confirming that the breakpoint is located between these two PAC clones. We also found that a region of approximately 500 kb between the two PAC clones was deleted. These results indicate that the locus between PAC clones 264m4 and 879n 10 at 18q21.1 involved in t(11;18) translocation or associated deletion plays an important role in the development of MALT lymphoma.

Chromosome Mapping↗

PubMed1999

[Primary pulmonary cryptococcosis diagnosed by medical examinations in 12 patients].

Primary pulmonary cryptococcosis is thought to be relatively less common than other lung mycoses, but recently there has been an increase in reports of patients with this disease. Our report covers 12 cases of primary pulmonary cryptococcosis in which the diagnosis was based on medical examinations. The patients consisted of 11 men and 1 woman, aged 27 to 58 years. Only 3 exhibited subjective symptoms. Roentgenograms showed cavitating tumor shadows in the lungs of 2 of the patients with subjective symptoms, and nodular shadows with diameters of 1.0 to 2.8 cm in all patients without subjective symptoms, indicating the possibility of lung cancer. The disease was diagnosed in 3 patients on the basis of transbronchial biopsy findings, and in 9 on the basis of needle aspiration biopsy findings. One patient was diabetic, but the others did not exhibit malignancies or other immunocompromised states. Antifungal drugs significantly reduced or eliminated the nodular shadows in 10 patients. Because patients with primary pulmonary cryptococcosis frequently lack subjective symptoms, prompt diagnosis is critical, particularly in view of the need to distinguish the disease from lung cancer.

Adult↗

PubMed1999

Cytotoxic large T-cell lymphoma with fulminant clinical course, CD8+ and CD56- phenotype, and its relation to Epstein-Barr virus: a report of two cases.

Currently, the immunohistochemical evaluation of cytotoxic granule-associated proteins such as TIA-1 and granzyme B can be carried out on paraffin sections. This procedure has broadened our knowledge of cytotoxic lymphoid neoplasms. Their detection is now regarded as a useful adjunctive in some characterizations of cytotoxic T- or natural killer (NK)-cell lymphoma, mostly in lymphoma of extranodal origin. We report two cases of nodal cytotoxic large T-cell lymphoma with identical biologic properties. Both cases presented with systemic lymphadenopathy, lymphomatous bone marrow involvement, and thrombocytopenia. The clinical course was fulminant, and both patients died within 1 week of presentation. The cells had a characteristic immunophenotype of CD2+, CD3+, CD4-, CD5-, CD8+, CD30 -/+, CD56-, CD57-, TCR alpha/beta+, and TCR gamma/delta-. They also expressed the cytotoxic granule-associated proteins of TIA-1 and granzyme B, and exhibited clonal rearrangements of the T-cell receptor beta chain gene. Monoclonal integration of Epstein-Barr virus was also detected. The present cases exhibited clinicopathological features that were distinct from other types of malignant lymphoma expressing cytotoxic granule-associated proteins.

Adult↗

PubMed1998

HA1077, a protein kinase inhibitor, inhibits calponin phosphorylation on Ser175 in porcine coronary artery.

Calponin is a thin filament-associated protein which has been implicated in the modulation of the contractile state of smooth muscle via its interaction with actin and inhibition of the actin-activated myosin Mg-ATPase. This inhibitory effect is alleviated by phosphorylation of calponin at Ser175 in vitro by protein kinase C. The issue of calponin phosphorylation in intact smooth muscle in response to agonists that activate protein kinase C is controversial. We have produced a monoclonal antibody that specifically recognizes calponin phosphorylated at Ser175 and used it to analyze calponin phosphorylation in porcine coronary arterial smooth muscle stimulated with prostaglandin F2alpha or phorbol 12,13-dibutylate (PDB). Calponin phosphorylation increased rapidly in response to prostaglandin F2alpha concomitant with the increase in tension. Calponin was then dephosphorylated while force was maintained. Tension development in response to PDB was significantly slower, but again calponin phosphorylation paralleled force development. In this case, calponin dephosphorylation was very slow, consistent with prolonged activation of protein kinase C. The protein kinase inhibitors, HA1077 (1-5-(isoquinoline sulfonyl)-homopiperazine HCl) and HA1100 (1-hydroxy HA1077; 1-(hydroxy-5-isoquinoline sulfonyl-homopiperazine), inhibited tension development and calponin phosphorylation in a concentration-dependent manner with similar ED50 values in response to prostaglandin F2alpha and PDB. These results support physiological roles for calponin in force development in smooth muscle in response to agonists which trigger protein kinase C activation and in the latch state, i.e., force maintenance at low energy cost. Furthermore, the vasodilator effect of HA1077 and HA1100 is more likely due to inhibition of protein kinase C than of myosin light chain kinase.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1998

Delineation of the breakpoint at 18q21.1 in a cell line (Karpas1106) derived from mediastinal B-cell lymphoma by fluorescence in situ hybridization with multiple YAC clones.

The breakpoint of the 18q21 translocation of B-cell-non-Hodgkin's lymphoma (NHL) cell line Karpas1106P was delineated by fluorescence in situ hybridization (FISH). Karpas1106P was derived from mediastinal lymphoblastic B-cell lymphoma and exhibited the immunophenotype characteristic of marginal-zone B-cell lymphoma (MZL): smIg+, pan-B antigen+, CD5-, CD10- and CD23-. The original G-banded karyotype showed a complex translocation containing t(X;18;13)(q28;q21;q12.1). Double-color FISH (DCFISH) with whole-chromosome-painting (WCP) probes for chromosomes X, 13 and 18, and 18q-specific yeast artificial chromosome (YAC) clones defined t(X;18;13) as ider(X)t(X;18; 13)(q28;q 12.3q21.1;q12.1). The immunoglobulin-heavy-chain (IgH) gene was not involved in the chromosomal translocation as detected by DCFISH with VH and Cgamma probes. By using contiguous YAC clones mapped from 18q12.3 to q21.1, we identified a YAC clone y852H2 with its breakpoint at 18q21.1. In Karpas1106P, the distal part of chromosome 18 from the breakpoint (18q21.1-qter) was deleted, showing loss of heterozygosity of this region. In addition, the chromosomal segment 18q21.1 was duplicated and inserted to ider(X)t(X;18; 13) between Xq28 and 13q12.1 with maintaining its original orientation. The DNA sequence of the breakpoint region contained in y852H2 can serve as a candidate locus for further molecular dissection to identify the causative gene of MZL.

Chromosome Mapping↗

PubMed1998

Antisense oligodeoxyribonucleotide against the MLL-LTG19 chimeric transcript inhibits cell growth and induces apoptosis in cells of an infantile leukemia cell line carrying the t(11;19) chromosomal translocation.

To clarify the role of the multiple lineage leukemia gene-leukemia translocation gene of chromosome 19 (MLL-LTG19) protein in leukemogenesis, we synthesized antisense oligodeoxyribonucleotide (ODN) against the fused region of the MLL-LTG19 chimeric transcript and treated KOCL33 cells carrying the t(11;19) translocation with antisense ODN. The antisense ODN inhibited cell growth and induced apoptosis in KOCL33 cells but not in Daudi cells, which have no t(11;19). The levels of MLL-LTG19 mRNA and MLL-LTG19 protein in KOCL33 cells treated with antisense ODN were shown to decrease with time by reverse transcription-PCR and Western blot analysis. These results suggest that the MLL-LTG19 fusion protein contributes to cell proliferation and malignant transformation in infantile acute leukemia cells carrying the t(11;19) translocation.

Apoptosis↗