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J P Meijerink

Publications and source records attributed to J P Meijerink.

14 recordsLinked to original sources
PubMed2001

Lack of correlation between numbers of circulating t(14;18)-positive cells and response to first-line treatment in follicular lymphoma.

In follicular lymphoma, the t(14;18) status of the peripheral blood and bone marrow analyzed by polymerase chain reaction (PCR) is assumed to correlate with disease activity in patients with relapsed disease. The clinical significance of quantitating circulating lymphoma cells by real-time PCR is reported in patients on first-line treatment. Thirty-four consecutive patients with previously untreated follicular lymphoma and detectable t(14;18)-positive cells in pretreatment peripheral blood samples were monitored. All patients were treated with standard chemotherapy in combination with interferon alfa-2b. Before and after induction therapy, blood samples were taken for quantitative analysis of t(14;18). At presentation, a median of 262 t(14;18)-positive cells per 75,000 normal cells was found (range, 1-75 000). Patients with lower numbers of circulating tumor cells more frequently had bulky disease (P =.02). Seventy-nine percent of the patients responded clinically to treatment. In 22 of 28 patients, including 4 patients in whom treatment had failed clinically, the number of circulating t(14;18)-positive cells decreased to undetectable or low levels after therapy. In the remaining responding patients, circulating tumor cells persisted after therapy. These quantitative data on circulating t(14;18)-positive cells call into question the usefulness of molecular monitoring of the blood in a group of patients with follicular lymphoma uniformly treated with a noncurative first-line regimen. T(14;18)-positive cells decreased in peripheral blood after treatment, irrespective of the clinical response. Therefore, the significance of so-called molecular remission should be reconsidered in follicular lymphoma. (Blood. 2001;98:940-944)

Adult↗
PubMed1999

Frequent allelic imbalance but infrequent microsatellite instability in gastric lymphoma.

Specific defects in DNA repair pathways are reflected by DNA microsatellite instability (MSI) and play an important role in carcinogenesis. Reported frequencies in gastric non-Hodgkin's lymphomas (NHL) vary from 14% to as high as 90%. Another form of genetic instability in tumours is allelic imbalance (AI) due to loss or gain of genetic material at a specific chromosomal region. This might point to the presence of a tumour suppressor gene or oncogene. We examined both MSI and AI in 26 gastric lymphomas (10 low-grade and 13 high-grade MALT lymphomas and three cases lacking MALT features and categorised as diffuse large B cell lymphoma (DLCL)). Tumour components and normal cells (epithelium, muscle) were microdissected from paraffin-embedded resection samples. Contrary to other studies we did not observe frequent MSI when investigating 18 different loci distributed over 12 chromosomes. Microsatellite instability of a single locus was found in 1/10 (10%) low-grade MALT lymphomas and 2/13 (15%) high-grade MALT lymphomas. These data indicate that DNA mismatch repair genes do not play a role in the pathogenesis of these lymphomas. Allelic imbalance was detected in 60% (6/10) of low-grade MALT lymphomas, in 62% (8/13) of high-grade MALT lymphoma and in 67% (2/3) of DLCL. In high-grade lymphomas more loci showed AI (one to seven loci, with a mean of 2.5 loci per case) than in the low-grade lymphomas (one to two loci, with a mean of 1.3 loci per case), possibly reflecting an increased genomic instability.

DNA Mutational Analysis↗
PubMed1998

Hematopoietic malignancies demonstrate loss-of-function mutations of BAX.

The BCL-2 gene family regulates the susceptibility to apoptotic cell death in many cell types during embryonic development and normal tissue homeostasis. Deregulated expression of anti-apoptotic BCL-2 can be a primary aberration that promotes malignancy and also confers resistance to chemotherapeutic agents. Recently, studies of Bax-deficient mice have indicated that the pro-apoptotic BAX molecule can function as a tumor suppressor. Consequently, we examined human hematopoietic malignancies and found that approximately 21% of lines possessed mutations in BAX, perhaps most commonly in the acute lymphoblastic leukemia subset. Approximately half were nucleotide insertions or deletions within a deoxyguanosine (G8) tract, resulting in a proximal frame shift and loss of immunodetectable BAX protein. Other BAX mutants bore single amino acid substitutions within BH1 or BH3 domains, demonstrated altered patterns of protein dimerization, and had lost death-promoting activity. Thus, mutations in the pro-apoptotic molecule BAX that confer resistance to apoptosis are also found in malignancies.

Animals↗
PubMed1997

t(14;18), a journey to eternity.

The t(14;18) is the most frequent chromosomal aberration observed in follicular non-Hodgkin's lymphoma (NHL), and less frequently in diffuse large cell lymphoma (DLCL). The t(14;18) does not affect overall survival in follicular NHL or DLCL. It provides a unique lymphoma-specific marker that can be used to quantify residual disease during treatment, and may forward evaluation of new treatment protocols. The t(14;18) results in the deregulation of bcl-2, a proto-oncogene that protects against induction of programmed cell death (PCD). Nowadays, a whole family of bcl-2-related genes has been identified and consist of members which can either protect or promote induction of PCD. The family members form protein dimers, and the relative abundance of specific dimers regulates the cellular sensitivity to death signals (the rheostat model). Aberrant expression of different family members in several types of malignancies alter the cellular rheostat and thereby promote cellular resistance to chemotherapy.

Amino Acid Sequence↗
PubMed1995

Parasitic apicomplexans harbor a chlorophyll a-D1 complex, the potential target for therapeutic triazines.

Ultrastructural evidence is presented for the presence of plastid-like organelles in Toxoplasma gondii, Sarcocystis muris, Babesia ovis, and Plasmodium falciparum. In addition, it was shown that merozoites of T. gondii contain protochlorophyllidae a and traces of chlorophyll a bound to the photosynthetic reaction centers I PS I and PS II. A psbA gene was isolated from merozoites of S. muris by the polymerase chain reaction (PCR). Partial sequencing of the PCR product revealed that the herbicide-binding region is highly conserved. Therefore, it is likely that the sensitivity of apicomplexans to the herbicide toltrazuril depends on the interaction of the herbicide with the D1 protein of the photosynthetic reaction center of the parasite's organelles.

Amino Acid Sequence↗
PubMed1995

New type of t(14;18) in a non-Hodgkin's lymphoma provides insight in molecular events in early B-cell differentiation.

In this report a follicular non-Hodgkin's lymphoma (NHL) carrying an unusual t(14;18) is described. This translocation most likely occurred during the VH to D-JH rearrangement process of the IgH locus. From the data combined with data from the literature we conclude that the chance for development of a t(14;18) decreases during progression of the immunoglobulin rearrangement process in the pre-B-cell ontogeny. This is probably due to decreased accessibility of the bcl-2 locus by reduced transcription. We analysed the somatic mutation pattern of the productively rearranged IgH gene. Like other follicular lymphomas, somatic mutations were present in this gene and indicated positive selection, probably for an antigen. We found no evidence for ongoing induction of somatic mutations during lymphoma development. We conclude that bcl-2 gene deregulation, but not the precise moment at which this occurs during the pre-B-cell stage, influences the development of follicular NHL.

Adult↗
PubMed1995

Bax mutations in cell lines derived from hematological malignancies.

Many genes are involved in cell cycle control, DNA repair and induction of cell death. Alterations in these genes have been responsible for the development of cancer as well as for resistance to cancer therapy. Recently, an emerging family of bcl2-like genes has been identified that plays a role in the regulation of cell death. Its members are highly conserved in several domains which have been shown to be important for homodimerization or heterodimerization. The ratio between BAX/BCL2 heterodimers and BAX/BAX homodimers appears to be pivotal in deciding the life of death of a cell. We recently detected mutations in evolutionary highly conserved domains of the bax gene in cell lines derived from hematologic malignancies. Similar artificially generated mutations in other bcl2-like family members bcl2, bclxl, or ced9 have been shown to alter their function. This suggests a role for bax mutations in the multi-step pathogenesis of hematological malignancies.

Base Sequence↗
PubMed1994

Quantitative analysis of DNA aberrations amplified by competitive polymerase chain reaction using capillary electrophoresis.

We compared the use of capillary electrophoresis (CE) in a polymer network with the use of slab gel electrophoresis for the quantitative analysis of polymerase chain reaction (PCR)-amplified DNA samples. We quantified residual lymphoma cells carrying a translocation between chromosomes 14 and 18, in consecutive patient peripheral blood samples that were amplified by competitive PCR. For CE analysis we used a 4% linear polyacrylamide network. Results show that the calculated number of translocations in patient samples using both analyses were comparable. We conclude that CE is a sensitive, non-radioactive, fast and accurate method for quantitation of competitive PCR products.

Autoradiography↗
PubMed1994

Quantitation of follicular non-Hodgkin's lymphoma cells carrying t(14;18) in a patient before and after allogeneic bone marrow transplantation.

BACKGROUND: A competitive PCR method was developed, enabling accurate quantitation of residual lymphoma cells carrying the t(14;18) in blood and bone marrow samples of follicular non-Hodgkin's lymphoma (NHL) patients during treatment. PATIENTS AND METHODS: A patient with residual lymphoma cells received an allogeneic bone marrow transplantation (BMT). Since BMT, the patient has been in continuing clinical complete remission. RESULTS: Using the competitive PCR and two-step PCR method, we were able to demonstrate a gradual decline in the number of lymphoma cells within consecutive patient blood and bone marrow samples after BMT. CONCLUSIONS: The competitive PCR is a suitable method for the detection of minimal residual disease. Further research might reveal the clinical relevance of data obtained by this method.

Adult↗
PubMed1993

Quantitation of follicular non-Hodgkin's lymphoma cells carrying t(14;18) by competitive polymerase chain reaction.

A competitive polymerase chain reaction (PCR) technique was developed to quantify residual malignant cells in the peripheral blood and bone marrow of patients with low-grade follicular non-Hodgkin's lymphoma carrying a translocation between chromosomes 14 and 18. Artificial segments were constructed imitating a translocation between chromosome 14 and 18. These artificial translocation segments were used as competitor molecules in the quantitative PCR. Serial dilutions of a known amount of patient-derived translocation segments were coamplified with a fixed number of competitor molecules, and a patient specific calibration curve was constructed. Several patient samples were coamplified with an equal number of competitor molecules and the number of t(14;18) translocations within the samples was calculated by comparison with the calibration curve. The method was demonstrated on samples of four follicular non-Hodgkin's lymphoma (NHL) patients. In a patient transplanted with allogeneic bone marrow declining numbers of residual lymphoma cells were observed. We conclude that the method is accurate, relatively fast and the general principle of this method can be applied to all malignancies with characteristic abnormalities on DNA or RNA level that are detectable by PCR.

Base Sequence↗
PubMed1993

Sporadic mutations of the p53 gene in multiple myeloma and no evidence for germline mutations in three familial multiple myeloma pedigrees.

The recent finding that eight out of 10 multiple myeloma cell lines have p53 gene mutations prompted us to examine the p53 tumour suppressor gene in 25 non-related multiple myeloma patients. None of 19 patient bone marrow samples available for Southern blot analysis showed rearrangements in the p53 gene and only one patient showed loss of the p53 locus. DNA encompassing exons 5, 7, and 8, where p53 mutations commonly cluster, was amplified by PCR. Single-strand conformation polymorphisms of the PCR-amplified exon 5 region were detected in two patients. Direct sequencing of the mutant band revealed that one patient had a C to T transition at codon 138 (Ala to Val) and one patient had a G to C transversion at codon 139 (Lys to Asn). p53 mutations in germline cells in hereditary cancer syndromes predispose the family members to the development of malignancies. We therefore searched for p53 germline mutations in exons 5, 7, and 8 in the affected individuals from three families each with two multiple myeloma patients (these patients include three individuals from the non-related group mentioned above). Using Southern blotting, polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing, no germline mutations were found. These results indicate that mutations in exons 5, 7, and 8 of the p53 gene are infrequent in multiple myeloma.

Adult↗