Alain Bernadou

Splenic marginal zone lymphoma with or without plasmacytic differentiation

We report a series of 31 cases of splenic marginal zone lymphomas with an enlarged spleen and a multimicronodular macroscopic pattern. Two groups, A and B, were distinguished based on the presence (A) or absence (B) of a lymphoplasmacytic component with monoclonal immunoglobulin expression in the cytoplasm. There were no differences between the groups as far as age, sex, spleen weight, and progression. The only difference was the presence in group A of a monoclonal serum component and autoimmune disorders, particularly autoimmune hemolytic anemia. In most cases in which a liver and/or bone marrow biopsy was performed, lymphomatous infiltration was detected. Seven cases had a seric monoclonal IgM of 5 g/L or more and liver or bone marrow infiltration, corresponding to the definition of Waldenströms macroglobulinemia. Lymphoma cells had a monocytoid, centrocytoid and, in group A, lymphoplasmacytic morphology. The lymphomatous cells were positive for CD20, CD45 RA, and bcl-2. They expressed IgD in 9 cases, partially in 6, and were negative for IgD in 9 of the 24 cases studied. Progression seems to be slow, with a long survival. Three patients presented with transformation into a large B-cell lymphoma, which was responsible for death in two patients.

A new set of monoclonal antibodies against acute lymphoblastic leukemia

Six monoclonal antibodies produced by immunization of Balb/c mice with common acute lymphoblastic leukemia (cALL) cells were tested against various types of normal and malignant tissues. ALB1 and ALB2 are directed to the cALL antigen (CALLA gp100); ALB6 recognizes a determinant of p24; ALB7, ALB8 and ALB9 have a pattern of reactivity similar to Ba1. None of these antibodies specifically identify cALL but they should be useful tools for diagnosis or depletion of bone marrow in autologous therapy in transplantation. In addition, the example of ALB6 which acts as a platelet aggregating agent, suggests that the study of other cell systems expressing the antigens associated with cALL may shed light on the function of these antigens and subsequently on the physiopathology of the leukemic cells.

Conformational change in fibrinogen induced by adsorption to a surface

Abstract It is of great interest to know whether proteins adsorbed on a solid surface are conformationally altered, particularly for the problem of blood-foreign surface interaction. With this aim in mind, we tested the reactivities of immobilized or soluble fibrinogen against monoclonal antibodies obtained by mouse immunization with fibrin derivatives. Using an immunoenzymological assay with a monoclonal antibody that revealed an epitope present in the D domain of the molecule but not exposed on soluble undegraded fibrinogen, we found that the binding of fibrinogen to polystyrene rendered the epitope accessible to the monoclonal antibody. We speculate with these results that a conformational alteration of fibrinogen occurred by adsorption to the solid phase. Such results may have important applications in the testing of artificial surfaces that are designed to come in contact with the circulation.

D‐dimer and CA 125 levels in patients with ovarian cancer during antineoplastic therapy prognostic significance for the success of anti‐cancer treatment

In patients with ovarian cancer before they receive chemotherapy, the level of fibrin degradation products (D‐dimer), is correlated with the tumor load. In this study, the evolution of D‐dimer was compared in patients receiving antineoplastic therapy with the evolution of the disease. The patients could be classified into three groups. In Group 1 (nine patients), both plasma CA 125 (a tumor‐associated antigen) and D‐dimer remained elevated; the prognosis was always poor. In Group 2 (eight patients), CA 125 and D‐dimer decreased simultaneously, complete remission was observed in two patients, and significant residual tumor was observed in the others. In Group 3 (nine patients), despite an important decrease in CA 125, D‐dimer remained elevated during therapy. In this group, complete remission was observed in six patients, and three others showed a large decrease in their tumor load. The combination of a decrease in CA 125 levels with a continuous enhanced level of D‐dimer during chemotherapy identified a subgroup of patients with a favorable prognosis.

A rapid method for detection of membrane antigens by immunofluorescence and its application to screening hybridoma antibodies.

Abstract Immunofluorescence is a laborious method of studying membrane antigens if a large number of tests has to be performed; but it does have the advantage of allowing analysis at the single cell level. Since washing and resuspending cells is time consuming, we have developed an accelerated technique. A simple device facilitates washing unfixed viable cells in microplates and can be used for all types of binding studies. We describe its application to screening hybridoma antibodies against human leukemic cells.

Relationship of histological subtypes to prognosis in early stage Hodgkin's disease: a review of 312 cases in a controlled clinical trial

To assess the prognostic significance of a newer histologic classification of Hodgkins disease (HD), microscope slides from the time of diagnosis of 312 clinical stage IA or B, IIA or B and IIIA patients were reviewed in 1987, 6-10 years after their participation in a radiochemotherapeutic trial (1976-1982). Overall, the diagnostic reproducibility of the Rye classification by the same pathologist was confirmed. However, a new analysis showed an improvement in the differential diagnosis between HD and non-Hodgkins lymphomas (NHL) by the identification of 24 NHL (8%) amongst the patients originally diagnosed as HD. Most of the NHL identified on review had been classified originally as mixed cellularity. On review, none of the new histological subtypes of HD was significant for prognosis of relapse-free survival or overall survival. Only identification of NHL was shown to have an independent prognostic value on relapse rate (P = 0.012) and on overall survival (P = 0.10). It is concluded that diagnosis of HD by itself remains, in 1988, the sole histologic factor influencing the prognosis of these patients.

Atypical T‐cell leukemia terminating Hodgkin's disease

A case of Hodgkins disease is described which developed into a terminal illness characterized by a malignant proliferation of T‐cells. The leukemic cells, after optical and ultrastructural analysis, were distinct from those of myelomonocytic, acute lymphoblastic, chronic lymphocytic as well as pro‐lymphocytic leukemia. Their relationship with the T‐cell lineage seemed to be confirmed by a highly positive E‐rosette test and by cytochemistry which showed focal positivity of acid phosphatase. The importance of this T‐cell malignant proliferation is discussed, especially with regard to cellular interactions in Hodgkins disease.

Defective cell migration in an ovarian cancer cell line is associated with impaired urokinase‐induced tyrosine phosphorylation

The urokinase receptor (u‐PAR), a protein anchored to cell membrane by a glycosyl phosphatidylinositol, plays a central role in cancer cell invasion and metastasis by binding urokinase plasminogen activator (u‐PA), thereby facilitating plasminogen activation. Plasmin can promote cell migration either directly or by activating metalloproteinases that degrade some of the components of the extra cellular matrix. However, the IGR‐OV1‐Adria cell line contains the u‐PAR but does not migrate even in the presence of exogenous u‐PA, although the parental IGR‐OV1 cell line migrates normally in the presence of u‐PA. We therefore investigated the role of cell signalling for u‐PA induced cell locomotion. We show that cell migration induced by u‐PA–u‐PAR complex is always associated with tyrosine kinase activation for the following reasons: (1) the blockade of the u‐PAR by a chimeric molecule (albumin‐ATF) inhibits not only the u‐PA‐induced cell migration, but also the signalling in IGR‐OV1 line; (2) the binding of u‐PA to u‐PAR on non‐migrating IGR‐OV1‐Adria cells was not associated with tyrosine kinase activation; (3) the inhibition of tyrosine kinase also blocked cell migration of IGR‐OV1. Therefore tyrosine kinase activation seems to be essential for the u‐PA‐induced cell locomotion possibly by the formation of a complex u‐PAR–u‐PA with a protein whose transmembrane domain can ensure cell signalling. Thus, IGR‐OV1 and IGR‐OV1‐Adria cell lines represent a good model for the analysis of the mechanism of u‐PA–u‐PAR‐induced cell locomotion.

Peripheral-T-Cell Lymphoma with Hemophagocytic Histiocytosis Localised to the Bone Marrow Associated with Inappropriate Secretion of Antidiuretic Hormone

A patient with high fever, loss of weight and profound pancytopenia is reported. Peripheral T-cell lymphoma with hemophagocytosis was diagnosed. Bone marrow was the only localisation of the lymphoma. At presentation there were (i) a coagulopathy consistent with hemophagocytic histiocytosis (ii) the features of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). These different abnormalities disappeared after chemotherapy and reappeared during each of the 2 periods of disease progression. The patient died 6 months after diagnosis without ever achieving complete remission. As far as we are aware this is the first case report of T-cell lymphoma with hemophagocytic syndrome localised to the bone marrow and associated with SIADH.

Lymphoblastic lymphoma/leukemia with convoluted nuclei. The question of its relation to the t-cell lineage studied in 13 patients

This work is devoted to the analysis of the nature of lymphoblastic lymphoma/leukemia with convoluted nuclei which were initially described by Barcos and Lukes. Ultrastructural, cytochemical, and immunologic features of tumor cells were investigated in patients chosen according to known morphologic criteria. Through results of the E rosette test, the patients were divided into two groups (E+ and E−). In the E+ group, the predominant features were sex (only men), the mediastinal localization, and the focal positivity of the acid phosphatase reaction. Cytotoxicity tests with rabbit antihuman T‐lymphocyte anti‐serum confirmed the results of the E rosette test in the 3 patients of the E+ group who were tested and were also positive in 2 patients from the E− group (1 of these 2 patients had the characteristics found in the E+ group and can thus be related to this group; the other patient had none of these characteristics). This raises the question of a leukemia arising from a less differentiated T‐cell but this interpretation is limited by the specificity of the anti‐T‐serum. Ultrastructural study defines more precisely the convoluted aspect but does not at present allow a distinction between the two groups.