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B Van Camp

Publications and source records attributed to B Van Camp.

At least 19 recordsLinked to original sources
PubMed1996

Follow-up of bone lesions in an experimental multiple myeloma mouse model: description of an in vivo technique using radiography dedicated for mammography.

The evolution of bone lesions in transplantable C57BL/KaLwRjj 5T mouse myeloma (MM) has been followed in vivo. Mice were anaesthetised and a radiograph of the pelvis and hind legs was performed by a radiograph dedicated for mammography. This is the first description of an in vivo technique under experimental conditions whereby the development of bone lesions owing to the MM growth was demonstrated.

Animals↗
PubMed1996

Granulocytic sarcoma (chloroma): a report of two cases.

Granulocytic sarcoma or chloroma is defined as an extramedullary solid tumor, composed of granulocytic precursor cells at various levels of differentiation. Granulocytic sarcoma is mostly associated with acute and chronic leukemia, rarely with polycythemia vera and myelofibrosis. The use of special immuno-histochemical stains is mandatory, because this tumor is often misdiagnosed as malignant lymphoma. We report two cases of granulocytic sarcoma (tonsil and ovary) associated with chronic myelogenous leukemia. We describe the first reported association of atypical CML and granulocytic sarcoma.

Adult↗
PubMed1995

The clonogenic precursor cell in multiple myeloma.

Multiple myeloma is characterized by the monoclonal expansion of plasma cells in the bone marrow. Although the predominant cell type is the plasma cell, the initial oncogenic transformation is considered to take place in a more immature B cell. There is still much controversy about this precursor cell type. Phenotypic analysis of bone marrow and peripheral blood revealed that in multiple myeloma a great diversity exists in the phenotype of the cells considered to be involved. Because of the lack of a myeloma specific genetic lesion it is very difficult to trace back the cell in which the transforming event, leading to multiple myeloma, took place. The only real clonal marker is the idiotype of the immunoglobulin molecule expressed by the myeloma cells. With recombinant DNA technology it is now possible to produce clonal markers for each individual myeloma patient which recognize only the immunoglobulin genes expressed by the myeloma cell and its precursors. The sequences of these myeloma immunoglobulin genes do reveal a lot of information about the stage in the B-cell differentiation pathway in which the oncogenic event might have taken place. The presence of somatic mutations in a non-random fashion without intraclonal variation leads to the conclusion that the precursor myeloma cell could not possibly be a pre-B cell or stem cell but has to be a mature B cell that has been in contact with antigen and has past through the phase of somatic mutation, like a memory B cell or plasmablast.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗
PubMed1995

Homing mechanisms in the etiopathogenesis of multiple myeloma.

Although multiple myeloma (MM) is characterized by a monoclonal expansion of plasma cells, it has been assumed that the tumor clone also includes more immature B cells. We could demonstrate by DNA sequence analysis of the variable region in immunoglobulin (Ig) heavy chain genes, that myeloma patients have peripheral blood monoclonal B cells that have not switched their Ig isotype but are somatically hypermutated. This finding suggests that myeloma originates from a germinal center B cell of the lymph node, most probably a memory B cell or B lymphoblast. The identification of these cells in the peripheral blood circulation implies that they must be equipped with homing receptors that allow them to migrate from the lymph node to the marrow environment. Within the marrow compartment these precursors will receive the appropriate differentiation signals to become mature tumor cells. The growth and survival of these bone marrow (BM) plasma cells is believed to be regulated by a functional interplay with the surrounding marrow stroma involving different adhesive mechanisms and the action of several cytokines. We found that myeloma plasma cells express several adhesion molecules (ICAM-1, N-CAM, CD44, VLA-4). Myeloma cell lines can bind to purified fibronectin (FN) using mostly the VLA-4 receptor. However this interaction contributes only partially to binding with intact stromal layers. In contrast, the post-HDM aplasia was significantly shortened in two of the schedule B patients (3 to 10 days) and was followed by a 25- to 165-fold increase in CD34+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗
PubMed1994

Evidence that the clonogenic cell in multiple myeloma originates from a pre-switched but somatically mutated B cell.

There is still much controversy about the precursor cell type in multiple myeloma (MM). Some authors claim that it is a pre-B cell, others state that it is a memory B cell or plasmablast. We have recently shown that the VDJ region of the MM immunoglobulin heavy chain gene is somatically hypermutated and antigen selected, without intraclonal variation or evolution in time. By using a patient-specific PCR approach we have now obtained evidence that the premyeloma cell can be situated in the pre-switched B-cell compartment and that heavy chain switching can occur without further somatic mutation. Based on the MM immunoglobulin sequences derived from the bone marrow, patient-specific CDR2 and CDR3 oligonucleotides were designed. B lymphocytes were separated from plasma cells based on the expression of CD19 and HLA class II or surface bound IgM using immunomagnetic beads. The expressed Ig sequences were amplified by RT-PCR using patient specific CDR2 primers and isotype specific primers (C mu, C gamma, and C alpha). Myeloma-specific Ig sequences were detected by a myeloma-specific CDR3 probe and sequenced. In one out of five cases we found in the peripheral blood clonally related IgM and IgA sequences with the same somatic mutations as the MM-IgG sequence. In another case of an IgG MM we found in the bone marrow clonally related IgA sequences with the same somatic mutations. These findings, together with the fact that myeloma-Ig genes contain somatic mutations without intraclonal variation, suggest that the clonogenic cell in multiple myeloma can originate from a pre-switched but somatically mutated B cell.

Amino Acid Sequence↗
PubMed1994

Production of fibronectin and adherence to fibronectin by human myeloma cell lines.

In the present study we examined the production of fibronectin (FN) in 10 human myeloma cell lines (HMCL). By Northern blot analysis we could detect the presence of FN-mRNA in most of these lines. A majority of the cell lines (LP-1, OPM1, SKMM-2, EJM, JJN3 and ARH-77) hybridized with two probes recognizing total FN while the mRNA of one cell line (LB84-1) was shown to hybridize also with a probe recognizing the EDA segment of cellular FN. In one cell line (L363) FN-mRnA could only be detected after PCR amplification. Using an enzyme-linked immunosorbent assay, we could also demonstrate that HMCL secrete FN in their culture medium. Seven myeloma cell lines that produce FN showed a significant adherence to soluble FN. By blocking experiments, this adhesion was found to be mediated by the VLA-4 (alpha 4 beta 1) receptor. The production of fibronectin and the expression of a functional receptor for this protein may represent independent features of myeloma cells but may also be functionally linked. Since fibronectin has recently been identified as a crucial co-factor of IL6 in the regulation of the terminal B cell differentiation, the endogenous FN production may be part of an autocrine-line process mediating the autonomous growth of these cell lines. Alternatively, the FN production may also reflect a mechanism that myeloma cells use to communicate with their natural environment, i.e. the bone marrow stroma.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1993

The involvement of adhesion molecules in the biology of multiple myeloma.

Multiple myeloma represents a B cell malignancy characterized by a monoclonal proliferation of plasma cells. A striking feature of the disease is the tendency of the malignant plasma cells to affect mainly the bone marrow environment and to invade the peripheral blood only in the terminal stage. The growth of myeloma plasma cells is believed to be regulated by a functional interplay between the tumor cells and the bone marrow stroma, involving the action of various cytokines. This growth control is most probably mediated by close cellular contact of the myeloma cells and marrow stromal components. Therefore it can be assumed that myeloma plasma cells possess the ability to interact with the bone marrow stroma. Until now the adhesive mechanisms that may underlie this interaction, remain undetermined. We investigated the expression of several adhesion molecules on bone marrow plasma cells in myeloma patients and normal controls. Normal as well as malignant plasma cells were found to be strongly positive for the intercellular adhesion molecule ICAM-1, the fibronectin receptor VLA-4 and the lymphocyte homing receptor CD44. In addition, a much weaker expression of the second fibronectin receptor VLA-5, the laminin receptor VLA-6 and the vitronectin receptor CD51 was demonstrated. In contrast to normal plasma cells, myeloma cells can also express the neural cell adhesion molecule N-CAM. In this report we discuss the possible role of adhesion molecules in the pathogenesis and clinical evolution of multiple myeloma.

B-Lymphocytes↗
PubMed1992

Evidence that multiple myeloma Ig heavy chain VDJ genes contain somatic mutations but show no intraclonal variation.

To investigate whether somatic hypermutation occurs in multiple myeloma (MM) Ig VH region genes, we have cloned and sequenced the expressed VH genes from five cases of MM. The sequences were obtained after polymerase chain reaction (PCR) on total RNA isolated from the bone marrow, using 5' VH family-specific leader and 3' C gamma- or C alpha-specific primers. MM-specific CDR3 oligonucleotides were produced to isolate VH genes expressed by the malignant plasma cells. In all five cases, the productive Ig gene used the VH3 family. Extensive sequence analysis of multiple independent M13 clones showed no intraclonal variation with no evidence for ongoing somatic hypermutation in MM VH region genes. We were able to identify possible germline counterparts of the expressed VH genes in two cases. Comparison of these genes shows that the MM VH region genes have somatic mutations characteristic for an antigen-driven process. In the other three cases, no close homology could be found with published VH3 sequences. These findings implicate that, in MM, clonal proliferation takes place in a cell type that has already passed through the phase of somatic hypermutation.

Adult↗
PubMed1992

Large granular lymphocyte proliferative disease: 21 Belgian cases and review of the literature.

We report the findings in 21 Belgian patients (12 males and 9 females, median age 61 years) with LGLPD. Symptoms at presentation included infection (n = 9), weight loss (n = 5), asthenia (n = 9), pruritus (n = 2) and arthralgia (n = 7). Four patients were asymptomatic. The main clinical findings were hepatomegaly (n = 5), splenomegaly (n = 8), lymph node enlargement (n = 3) and arthritis (n = 5). All patients had an increased LGL count associated with anemia (n = 12), neutropenia (n = 17), often less than 0.5.10(9)/L (n = 10) and thrombocytopenia (n = 6). Three patterns of lymphocyte surface markers were observed: CD3+CD4-8+ (14 patients), CD3+CD4-8+ (5 patients) and CD3+CD4+8- (1 patient). An abnormal karyotype was found in 2 patients. T-cell receptor gene was rearranged in all cases tested (9/9).

Adult↗
PubMed1992

Chemotherapy-induced acral erythema and acute graft-versus-host disease after allogeneic bone marrow transplantation.

Chemotherapy-induced acral erythema is a rare disorder characterized by a painful and intense erythema of the palms and the soles. In allogeneic bone marrow transplant patients, the differential diagnosis of acute graft-versus-host disease (AGVHD) may be difficult. We describe a case of concurrent acral erythema and AGVHD. The clinical features of both conditions as well as the histological findings on serial skin biopsy specimens are discussed.

Acute Disease↗
PubMed1991

Leukemia and lymphoma immunophenotyping in cell smears with immunogold-silver staining.

The potential of the immunogold-silver staining (IGSS) technique for immunophenotyping leukemia and lymphoma cells in cell smears was examined. Peripheral blood, bone marrow aspirates, lymph node biopsy specimens, fine-needle aspirates, and biologic fluids of 83 patients with acute or chronic leukemias, non-Hodgkin's lymphomas, or Hodgkin's disease were labeled. Cell smears, cytocentrifuge preparations, or imprints were fixed, incubated with the reagents, and counterstained with May-Grünwald-Giemsa. Stable immunostaining and good morphologic characteristics allowed accurate cell identification and rapid enumeration of the positive cells. The immunophenotypes obtained with the use of 35 monoclonal antibodies with different specificities were similar to those determined by flow cytometry or immunohistochemical studies on the same samples. This IGSS method was especially useful for the examination of poor samples or complex cell suspensions with rare malignant cells. It could be an alternative to the immunoenzyme methods that generally are used for this purpose.

Antibodies, Monoclonal↗
PubMed1991

Expression of cytoadhesion molecules (CD56, CD54, CD18 and CD29) by myeloma plasma cells.

Recently we reported the expression of the human natural killer cell associated antigen CD56 (Leu 19/NKH1) in plasma cells of a majority of multiple myeloma (MM) patients. CD56 is known to be an isoform of the human neural adhesion molecule N-CAM which is involved in homotypic adhesive interactions. By immunophenotyping using four CD56 specific monoclonal antibodies and immunoprecipitation analysis we here confirm that the Leu 19 antigen expressed by myeloma plasma cells is identical to N-CAM and corresponds to the 145 kDa isoform. Because of the possible biological role of adhesion molecules on myeloma cells, we compared the expression of N-CAM with the intercellular adhesion molecule 1 (ICAM-1) and the beta 1 and beta 2 integrins. By immunogold-silver staining of cytospin preparations of mononuclear cell suspensions, bone marrow plasma cells of 17 MM patients were analysed. Plasma cells expressed N-CAM (CD56) in 14 patients. ICAM-1 (CD54) in 16 patients, and beta 2 integrins (CD18) in eight patients. beta 1 integrins (CD29) were expressed in all patients. The expression of beta 2 integrins was always very weak while N-CAM, ICAM-1 and the beta 1 integrins showed a moderate to strong positivity. The plasma cells of five haematological normal individuals lacked significant N-CAM expression but were positive for ICAM-1 and both integrin subgroups. One plasma cell leukaemia patient and two out of four end-stage MM patients showed no expression of N-CAM or beta 2 integrins on their circulating plasma cells. Among 11 previously established myeloma cell lines, surface expression of ICAM-1 and the integrins was detected in most cases, while N-CAM was present in only four lines. Most cell lines showed coexpression of the fibronectin receptors (VLA-4 and VLA-5) and the laminin receptor (VLA-6). The collagen receptor (VLA-2) was not expressed. The N-CAM negative cell lines included four cell lines that were derived from plasma cell leukaemia patients. These results indicate that the expression of adhesion molecules is an intrinsic part of the biology of multiple myeloma.

Antigens, CD↗
PubMed1990

Plasma cells in multiple myeloma express a natural killer cell-associated antigen: CD56 (NKH-1; Leu-19).

Bone marrow samples from 55 patients with multiple myeloma (MM) and 23 patients with monoclonal gammopathy of undertermined significance (MGUS) were evaluated with a broad panel of monoclonal antibodies. Plasma cells from 78% (43/55) of patients with MM strongly expressed the natural killer cell antigen CD56 (NKH-1, Leu-19). Of the 23 patients with MGUS, none showed strong CD56 reactivity, although three had weak reactivity in less than 20% of plasma cells. Myeloma cells expressing CD56 did not coexpress the CD57 or CD16 antigens. Patients with CD56-positive plasma cells had both indolent and aggressive disease. However, the 12 CD56-negative patients had predominantly aggressive disease with an unexpected preponderance of kappa Bence Jones only myeloma (5/10[50%] evaluable patients). Polyclonal plasma cells from non-neoplastic tissue sites (normal bone marrows, lymph nodes, tonsillar biopsies, and gut-mucosa biopsies) showed a near absence of CD56. We conclude that isolated, strong CD56 expression is common in MM, but not in MGUS or reactive plasma cells. The potential biologic importance of CD56 positivity in myeloma is reviewed.

ADP-ribosyl Cyclase↗
PubMed1990

Immunomagnetic purging of bone marrow grafts for autologous transplantation in neuroblastoma.

Bone marrow grafts of 5 patients with stage IV neuroblastoma and one patient with stage IV retinoblastoma were harvested during complete remission and in vitro processed for autologous transplantation. Because of the risk to reinfuse metastatic cells, the grafts were immunomagnetically purged. After preparation of the buffy coat fraction, mononuclear cells (mnc) and progenitor cells (CFU-GM) were enriched by density centrifugation and incubated successively with a cocktail of five tumour reacting monoclonal antibodies and magnetic microparticles. Target cells were removed by a set of samarium cobalt magnets. The purged grafts were stored in liquid nitrogen. After the complete procedure, an average of 16% nucleated cells of the initial harvest could be recovered. This corresponds with a mean number of 0.5 X 10(8) mnc and 2.4 X 10(4) CFU-GM per kg body weight being available for grafting. So far, 5 patients received their purged marrow graft and showed a sustained take.

Bone Marrow Cells↗