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M Bentz

Publications and source records attributed to M Bentz.

At least 37 records · Page 2Linked to original sources
PubMed2000

Primary gastric apoptosis-rich T-cell lymphoma co-expressing CD4, CD8, and cytotoxic molecules.

In contrast to primary gastric lymphomas of B-cell type, little is known about primary gastric T-cell lymphomas. We describe three cases with remarkably similar features: diffuse growth, epitheliotropism, medium too large cell size, high apoptotic rates, and a CD3+, CD4+, CD8+, CD45RO+ immunophenotype. Clonal TCRgamma gene rearrangement was shown in two cases. Epstein-Barr virus infection was excluded in two cases. Taking advantage of fresh-frozen material, we analyzed two cases further, revealing CD5-, CD16+, CD56-, CD57-, CD25+, CD30+, CD103 (alphaEbeta7)+, bcl-2 protein+, CD95+, CD95 ligand(L)-. CD95L, however, was detected in histiocytic and fibroblastoid by stander cells. The lymphomas expressed granzyme B, perforin, and the TIA-1 antigen in various combinations. All three cases had a very unfavorable clinical course characterized by local recurrence and/or dissemination to other epithelial sites, leading to death within 6-12 months after the initial diagnosis despite surgery and aggressive antineoplastic treatment. These data suggest a novel variant of peripheral T-cell lymphoma operationally characterized as primary gastric, apoptosis-rich, CD103+, EBV-, T-cell lymphoma co-expressing CD4, CD8, CD16 and cytotoxic molecules.

Adult↗
PubMed2000

Comparative genomic hybridization: uses and limitations.

Comparative genomic hybridization (CGH) has contributed significantly to the current knowledge of genomic alterations in hematologic malignancies. Characteristic patterns of genomic imbalances not only have confirmed recent classification schemes in non-Hodgkin's lymphoma, but they provide a basis for the successful identification of genes with previously unrecognized pathogenic roles in the development of different lymphomas. Based on its technical limitations, there is little reason to apply CGH to chromosomes of metaphase cells in routine diagnostic settings. However, the new approach of CGH to DNA microarrays, a procedure termed matrix-CGH, overcomes most of the limitations and opens new approaches for diagnostics and identification of genetically defined leukemia and lymphoma subgroups. Current efforts to develop leukemia specific matrix-CGH DNA chips, which are designed to meet the clinical needs, are presented and discussed.

Hematologic Neoplasms↗
PubMed2000

BCL10 is not the gene inactivated by mutation in the 1p22 deletion region in mantle cell lymphoma.

The BCL10 gene has recently been cloned from the 1p22 breakpoint of the translocation t(1 ;14)(p22;q32) observed in mucosa-associated lymphoid tissue (MALT) lymphoma. BCL10 was shown to be a proapoptotic-signaling gene encoding a protein that contains an amino-terminal caspase recruitment domain (CARD). Mutations within the BCL10 coding region resulting in truncated BCL10 proteins with loss of their proapoptotic function and preservation of their NF-kappaB activating function were detected in MALT lymphoma. Based on these findings it was proposed that BCL10 might have tumor suppressor function. Deletions involving 1p22 are commonly observed in mantle cell lymphoma (MCL). To investigate its role in MCL we have analyzed a series of 15 MCL for deletion and mutation of BCL10. Monoallelic 1p22 deletions were detected by fluorescence in situ hybridization in five of the 15 cases and were shown to affect BCL10 in all cases. BCL10 was screened for mutations by DNA sequencing of RT-PCR amplified transcripts. In none of the 15 MCL cases studied were mutations found in the BCL10 coding region. A previously reported polymorphism exhibiting a silent 24C > G substitution was found in eight MCL cases and in four healthy probands. A missense mutation 13G >T resulting in a substitution of a serine by an alanine was seen in one of the controls. Our results strongly suggest that BCL10 is not the candidate tumor suppressor gene inactivated by deletion or mutation in band 1p22 in MCL.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Molecular analysis of the CDR3 encoding region of the immunoglobulin heavy chain locus in cerebrospinal fluid cells as a diagnostic tool in lymphomatous meningitis.

The diagnosis of leptomeningeal B-cell lymphoma is based on the identification of malignant B cells in the cerebrospinal fluid (CSF). Frequently, cytology does not allow clear distinction between neoplastic lymphoid cells and reactively transformed mononuclear cells. Individual B-cell clones can be identified on the basis of DNA sequences that encode the highly diverse complementarity-determining region (CDR3) of the immunoglobulin heavy chain locus (IgH). We studied CSF samples from 5 patients with B-cell malignancies and cytological evidence of leptomeningeal involvement, using polymerase chain reaction (PCR)-based high-resolution capillary electrophoresis and automated fluorescence analysis to detect PCR fragments. As controls, we assessed CSF specimens from 7 patients with inflammatory neurological diseases and three samples without pathological findings. In all patients with B-cell malignancies, a single PCR product was generated, indicating that CDR3-specific fragments were derived from monoclonal cell populations. CSF samples from patients with inflammatory diseases yielded multiple CDR3 amplicons, suggesting the presence of a polyclonal B-cell activation. No PCR product could be amplified in normal CSF samples. Automated fluorescence detection of CDR3 fragments is a highly sensitive and rapid method to distinguish neoplastic monoclonal and reactive polyclonal B-cell populations in the CSF.

Base Sequence↗
PubMed2000

t(11;14)-positive mantle cell lymphomas exhibit complex karyotypes and share similarities with B-cell chronic lymphocytic leukemia.

Until now, few data on additional chromosomal aberrations in t(11;14)-positive mantle cell lymphomas (MCLs) have been published. We analyzed 39 t(11;14)-positive MCLs by either comparative genomic hybridization (CGH; n = 8), fluorescence in situ hybridization (FISH) with a set of DNA probes detecting the most frequent aberrations in B-cell neoplasms (n = 12), or both techniques (n = 19). The t(11;14) was present in all cases. In 37 of 39 cases, chromosomal imbalances were found. In 27 cases, complex karyotypes, i.e., >/= 3 aberrations, were identified. The most frequent aberrations were losses of 13q14-21 or 13q32-34 (27 cases), 9p21 (16 cases), and 11q22-23 (12 cases) and gains of 3q26-29 (19 cases), 8q22-24 (11 cases), and 18q21-22 (9 cases). In 26% of cases (7 of 27) analyzed by CGH, a total of 10 high-level DNA amplifications were identified. Although in comparison with B-cell chronic lymphopcytic leukemia (B-CLL) MCL is characterized by a much higher complexity of chromosomal aberrations, there are striking similarities: 13q14 deletions were identified in more than 50% of both MCL and B-CLL cases. In contrast, in our CGH database containing 293 B-cell lymphomas, this aberration was found in only 11% of other nodal lymphomas. Even more strikingly, 11q deletions, which are present in 20%-30 % of MCL and B-CLL, were found very rarely in other nodal B-cell lymphomas (CGH: 1 of 208 cases; FISH: 1 of 69 cases). These data show that MCL is characterized by specific secondary aberrations and that there may be similarities in the pathogenesis of MCL and B-CLL. Genes Chromosomes Cancer 27:285-294, 2000.

Aged↗
PubMed2000

The ATM gene in the pathogenesis of mantle-cell lymphoma.

BACKGROUND: Mantle-cell lymphoma (MCL) is genetically characterized by the translocation t(11;14)(q13;q32) leading to an overexpression of cyclin-D1, but additional chromosomal abnormalities appear to be required for MCL pathogenesis. PATIENTS AND METHODS: Deletions involving chromosome 11q, which were recently found as recurrent aberrations in MCL, were analyzed at the molecular level in a series of 81 MCL by fluorescence in situ hybridization (FISH) with probes from a contiguous set of yeast artificial chromosomes (YACs) spanning bands 11q14-q24. RESULTS AND CONCLUSIONS: Loss of chromosome 11 material was observed in 37 of the 81 MCL cases (46%). The consensus deletion comprised YAC 801e11 containing the ATM gene. The minimal region of loss was further narrowed with P1-derived artificial chromosome (PAC) probes. This allowed the identification of a deletion confined to the genomic region of ATM, which, together with intragenic mutations found in the coding sequence, suggests a role of ATM as a tumor suppressor gene in MCL.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1999

Molecular characterization of 11q deletions points to a pathogenic role of the ATM gene in mantle cell lymphoma.

Deletions involving the long arm of chromosome 11 (11q) have been recently found as recurrent chromosome aberrations in mantle cell lymphoma (MCL). In the current study, the incidence and molecular extent of 11q deletions were analyzed in a series of 81 MCL by fluorescence in situ hybridization with probes from a contiguous set of yeast artificial chromosomes (YACs). Loss of chromosome 11 material was observed in 37 of 81 cases (46%). The minimally deleted segment comprised YAC 801e11 containing the ATM gene. To further narrow the minimal region of loss, P1-derived artificial chromosomes mapping to the critical region were isolated and used as probes in cases without aberrations detectable with YACs. This allowed the identification of an ATM deletion that was beyond the resolution of YAC probes. The identification of a minimally deleted segment affecting ATM suggests a pathogenic role of ATM as a tumor suppressor gene in MCL.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1999

IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn's disease: expression and localization in intestinal mucosal cells.

IL-18, a novel immunoregulatory cytokine with potent IFN-gamma-inducing activities, may play an important role in Th1-mediated chronic inflammatory disorders. The aim of the present study was to characterize the expression and localization of IL-18 in colonic specimens and isolated mucosal cell populations from patients with Crohn's disease (CD), a prototypic Th1-mediated disorder. Using a semiquantitative RT-PCR protocol, IL-18 mRNA transcripts were found to be increased in freshly isolated intestinal epithelial cells (IEC) and lamina propria mononuclear cells (LPMC) from CD compared with ulcerative colitis (UC) and noninflamed control (cont) patients, and were more abundant in IEC compared with LPMC. Immunohistochemical analysis of surgically resected colonic tissues localized IL-18 to both LPMC (specifically, macrophages and dendritic cells) as well as IEC. Staining was more intense in CD compared with UC and cont, and in involved (inv) vs noninvolved (n inv) areas. Western blot analysis revealed that an 18. 3-kDa band, consistent with both recombinant and mature human IL-18 protein, was found predominantly in CD vs UC intestinal mucosal biopsies; a second band of 24 kDa, consistent with the inactive IL-18 precursor, was detected in n inv areas from both CD and UC biopsies and was the sole form found in noninflamed cont. To our knowledge, this report is the first describing increased expression of IL-18 in a human Th1-mediated chronic inflammatory disease. In addition, our studies further support the concept that IEC and dendritic cells may possess important immunoregulatory functions in both normal, as well as pathological, mucosal immunity.

Adjuvants, Immunologic↗
PubMed1999

Deletions below 10 megabasepairs are detected in comparative genomic hybridization by standard reference intervals.

Comparative genomic hybridization (CGH) is a widely used technique for studying chromosomal imbalances. The sensitivity of the technique is, however, relatively low. Deletions down to a size of 10-12 Mbp have been detected by the use of fixed diagnostic thresholds. In this study, we applied standard reference intervals as detection criteria on a number of deletions in the range of 3 Mbp to 14-18 Mbp. All deletions were detected. Thus, detection by standard reference intervals confers a considerably higher sensitivity to CGH analysis compared to fixed diagnostic thresholds. Genes Chromosomes Cancer 25:410-413, 1999.

Chromosome Aberrations↗
PubMed1999

Chromosome aberrations in B-cell chronic lymphocytic leukemia: reassessment based on molecular cytogenetic analysis.

In B-cell chronic lymphocytic leukemia (B-CLL) clonal chromosome aberrations are detected in approximately 40-50% of tumors when using conventional chromosome banding analysis. Most studies find trisomy 12 to be the most frequent chromosome aberration, followed by structural aberrations of the long arm of chromosomes 13 and 14. Trisomy 12 and the "14q+" marker are associated with shorter survival times, while the patients with 13q abnormalities have a favorable outcome, similar to those with a normal karyotype. The development of molecular cytogenetic techniques has greatly improved our ability to detect chromosome aberrations in tumor cells. Using fluorescence in situ hybridization, chromosome aberrations can be detected not only in dividing cells but also in interphase nuclei, an approach referred to as interphase cytogenetics. The prevalence of specific aberrations in B-CLL is currently being reassessed by interphase cytogenetics. By far the most frequent abnormality are deletions involving chromosome band 13q14, followed by deletions of the genomic region 11q22.3-q23.1, trisomy 12, deletions of 6q21-q23, and deletions/mutations of the TP53 tumor suppressor gene at 17p13. The evaluation of the true incidence of these aberrations now provides the basis for more accurate correlations with clinical characteristics and outcome. Deletions/mutations of the TP53 gene have been shown to be associated with resistance to treatment and to be an independent marker for poor survival. 11q deletions have been associated with extensive nodal involvement, rapid disease progression, and short survival times. Whether trisomy 12, 13q14, and 6q deletions have a prognostic impact awaits further study. The application of these molecular cytogenetic techniques will also contribute to the identification of the pathogenetically relevant genes that are affected by the chromosome aberrations in B-CLL.

Animals↗
PubMed1999

Incidence and clinical significance of 6q deletions in B cell chronic lymphocytic leukemia.

Deletions affecting the long arm of chromosome 6 (6q) are among the most commonly observed chromosomal aberrations in lymphoid malignancies and have been identified as adverse prognostic factor in subsets of tumors. Whereas at least two regions of minimal deletion have been established, one in 6q21-q23 and another in 6q25-q27, no tumor suppressor gene that might be involved in the pathogenesis of lymphoid malignancies has been so far identified from these segments. For B cell chronic lymphocytic leukemia (B-CLL) conflicting data have been reported regarding the incidence and prognostic significance of 6q deletions. In the current study we have used two YAC clones mapping to deletion regions in bands 6q21 and 6q27 as probes for fluorescence in situ hybridization (FISH) in a large series of B-CLL cases to analyze the incidence, localization and clinical significance of 6q aberrations. Among 285 patients with B-CLL studied we identified 21 cases (7%) with 6q deletions. All deletions were found with the probe mapping to 6q21 while the 6q27 region was deleted only in a third of these cases. Analysis of the clinical characteristics and laboratory parameters showed that the patients with 6q deletions had higher white blood cell counts and more extensive lymphadenopathy. However, the overall survival and the treatment-free intervals were similar in the two groups. We conclude that deletions in 6q21 occur in 7% of B-CLL and identify a subgroup of patients characterized by a larger tumor mass but no inferior outcome.

Chromosome Deletion↗
PubMed1999

Induction of neutrophil calcium mobilization by phosphatidic acid-enriched plasma membranes.

The purpose of this investigation was to determine if phosphatidic acid (PA) confined to biological membranes could induce physiological responses similar to those induced by exogenous PA. Plasma membranes were treated with phospholipase D (PLD) to increase concentrations of PA within the membranes. Membranes were also treated with other phospholipases including phospholipase A2 (PLA2), and phospholipase C (PLC), which degrade phospholipids without generating PA. A phosphatidylinositol (PI) 3'-kinase inhibitor, LY294002, strongly and selectively inhibited intracellular calcium mobilization induced by PLD-treated membranes. This study suggests that PA-enriched plasma membranes, which exert their effects by activating a unique signaling pathway mediated by PI 3'-kinase, are potent, physiologically relevant initiators of neutrophil activation.

Benzoquinones↗
PubMed1999

Subtotal maxillectomy for melanotic neuroectodermal tumor of infancy.

Melanotic neuroectodermal tumor of infancy is a rare pigmented neoplasm occurring in infants before 1 year of age. It is a rapidly growing tumor that most frequently affects the craniofacial skeleton. Although melanotic neuroectodermal tumor of infancy is benign in the vast majority of cases, inadequate excision, occasional multicentricity, and a small malignant potential result in a fairly high recurrence rate. On the basis of data obtained from the literature and our clinical experience, we advocate an aggressive surgical approach consisting of complete surgical excision when vital structures are not involved. Histopathologic confirmation of complete excision is mandatory to minimize the risk of recurrence and provide the patient with curative treatment and minimal morbidity.

Humans↗
PubMed1999

Chromosomal aberrations in lymphomas of the gastrointestinal tract.

B-cell lymphomas of the gastrointestinal (GI) tract have represented a field of extensive research ever since a close association was shown with chronic inflammatory processes such as Helicobacter pylori infection. Much evidence has accumulated to suggest that the mucosa-associated lymphoid tissue (MALT) induced by inflammation and autoimmune processes is the environment which gives rise to the small cell lymphomas of the GI tract (e.g. extranodal marginal B-cell lymphoma according to REAL). The small B-cell lymphoma may then progress to the large cell variants. Hence, B-cell lymphomas of the GI tract may present a model for lymphomagenesis and progression. In this review, recent cytogenetic data are discussed which yield new insights into the biology of gastrointestinal lymphomas.

Chromosome Aberrations↗
PubMed1998

Characteristic pattern of chromosomal gains and losses in primary large B-cell lymphomas of the gastrointestinal tract.

In contrast to low-grade B-cell lymphomas originating in the gastrointestinal (GI) tract, only few cytogenetic data are available for the large cell, highly malignant variants. We studied 31 large B-cell lymphomas of the GI tract by comparative genomic hybridization (CGH) and fluorescence in situ hybridization using specific DNA probes (FISH). The most frequent aberrations were gains of all or of parts of chromosomes 11 (11 cases), 12 (9 cases), 1q (4 cases), and 3q (4 cases). Losses of parts of chromosome 6q and of parts of the short arm of chromosome 17 (6 cases each) were found most frequently. In four cases a total of seven high-level DNA amplifications was detected. In two of these cases, involvement of specific protooncogenes (REL and MYC) was shown. Some genetic aberrations seemed to be associated with an inferior clinical course: patients with >/=2 aberrations had a significantly shorter median survival. Furthermore, all patients with gains of all or parts of chromosome arm 1q and with high-level DNA amplifications as well as seven of nine patients with gains of all or parts of chromosome 12 died of lymphoma. In conclusion, the pattern of chromosomal gains and losses in large B-cell lymphomas was different from data reported for low-grade (MALT) lymphomas of the stomach and bowel, especially with respect to the high incidence of partial gains of chromosome arm 11q and of all or parts of chromosome 12 and the low frequency of polysomy 3. In addition, our data suggest that chromosomal gains and losses detected by CGH and FISH may predict for the outcome of patients with this tumor entity.

Adult↗