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B Drenou

Publications and source records attributed to B Drenou.

At least 19 recordsLinked to original sources
PubMed2006

Administration of rituximab during the first trimester of pregnancy without consequences for the newborn.

Rituximab, a chimeric mouse/human monoclonal antibody that binds to the CD20 antigen, is part of current treatment of many B-cell malignancies and several autoimmune diseases. Very few cases of rituximab administration during pregnancy have been described. We report here the case of rituximab administration during the first trimester of pregnancy in a woman with autoimmune hemolytic anemia. No significant effects were observed in B-cell counts or the immune status of the newborn.

Adrenal Cortex Hormones↗
PubMed2003

[Contribution to the detection of Melan-A/Mart-1 specific CD8+ T cells in surgery of melanoma. Preliminary study].

Melanoma treatment is based on surgery. In metastatic cases, vaccine therapy has been recently developed to overcome T cell or dendritic cell dysfunction. HLA tetramerbased assays are useful for immunologic monitoring of this trial and to quantitate CD8+ specific lymphocytes. In the present work, we used tetrameric technology to detect expanded populations of tumor specific CD8+ Tcells specific of Melan-A/Mart-1 Antigen have been quantified using flow cytometry. The feasibility of routinely detection of 0,1% +/- 0,03 of CD8 T cells has been demonstrated, without any difference the levels observed before and after (day 30) surgery. The value of experimentation of these cells should be determined in clinic and particularly to analyze surgical practice.

Adult↗
PubMed2002

High multidrug resistance protein activity in acute myeloid leukaemias is associated with poor response to chemotherapy and reduced patient survival.

Multidrug resistance protein (MRP) activity was investigated in 44 newly diagnosed acute myeloid leukaemia (AML) patients using a functional assay based on efflux of carboxy-2',7'-dichlorofluorescein, an anionic dye handled by both MRP1 and MRP2. Elevated MRP transport was detected in 29% of cases, but was not significantly correlated with sex, age, white blood cell count at diagnosis or karyotype. In contrast, it was associated with secondary AML (P = 0.002), CD34 positivity (P = 0.041) and P-glycoprotein activity (P = 0.01). There was a lower rate of complete remission in MRP-positive patients versus MRP-negative patients (23% versus 81%; P = 0.001); overall survival was also better for MRP-negative patients (P = 0.004). These data indicate a probable role for MRP activity in the clinical outcome of AML.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

Jumping translocation in acute leukemia of myelomonocytic lineage: a case report and review of the literature.

Jumping translocation (JT) is a very rare cytogenetic event, occurring especially in cancer. We describe a case of secondary acute monocytic leukemia (AML5b) with a JT involving the 3q13-3qter segment and leading to a partial trisomy 3. Each clone with JT was associated with trisomy 8 or tetrasomy 8. The literature of JT in AML cases is reviewed: only 13 cases of AML associated with JT have been previously described, seven of which are AML4/5 FAB subtype. Jumping translocation involvement in leukemogenesis is discussed. Leukemia (2000) 14, 119-122.

Adult↗
PubMed1999

HLA-G protein expression is not induced during malignant transformation.

To evaluate the biological relevance of HLA-G expression during tumoral transformation, we analyzed its expression in different malignant cells and immune effector cells infiltrating solid tumors. Our analysis of 33 tumor cell lines and 53 tumoral biopsies demonstrated that: i) six tumor cell lines display HLA-G transcription with differential alternative splicing patterns and only Jeg3 choriocarcinoma and MCF-7 breast adenocarcinoma cell lines express HLA-G translated products; and ii) HLA-G antigens are not expressed in malignantly transformed cells derived from lung (n=18), liver (n=5), colon (n=5), breast (n=10), kidney (n=5), ovary (n=5), and larynx (n=5) tissues ex vivo. The healthy tissues surrounding these tumor tissues do not express HLA-G molecules either. On the other hand, surprisingly, HLA-G products were detected in activated macrophages and dendritic cells localized in tumoral biopsies of 5 out of 18 different lung carcinomas. No HLA-G labelling was observed in resident mononuclear phagocytes of surrounding healthy tissues. Our observations clearly demonstrate that HLA-G is not a marker of malignant cells but appears as a gene expressed in tumor-associated macrophages and dendritic cells, preferentially in those recruited in lung carcinomas. Our findings suggest that specific environmental factors around lung tumors could be involved in the induction of HLA-G protein expression.

Cell Movement↗
PubMed1999

Use of the anionic dye carboxy-2',7'-dichlorofluorescein for sensitive flow cytometric detection of multidrug resistance-associated protein activity.

Multidrug resistance-associated protein (MRP) and P-glycoprotein are drug efflux pumps conferring multidrug resistance to tumor cells and sharing numerous substrates. In order to determine a flow cytometric assay allowing to analyse MRP activity in cancerous cells in a sensitive and specific manner, cellular accumulation and efflux of the anionic fluorescent dye carboxy-2',7'-dichlorofluorescein (CDF) were studied by flow cytometry using mainly MRP-overexpressing lung GLC4/Sb30 cells and parental GLC4 cells. GLC4/Sb30 cells were found to display reduced accumulation and enhanced efflux of the dye when compared to their parental counterparts. Probenecid, a well known blocker of MRP, strongly enhanced CDF accumulation in GLC4/Sb30 cells through inhibiting efflux of the dye; it also increased CDF levels in GLC4 cells, although to a lesser extent, which may likely be linked to the low, but detectable, expression of MRP in these cells. Comparison of CDF retention with that of calcein demonstrated that the former dye was the most efficiently effluxed by GLC4/Sb30 cells. In contrast to MRP overexpression, that of P-glycoprotein was not found to alter cellular CDF labelling whereas it strongly impaired calcein staining. These results indicate that CDF is a substrate for MRP, but not for P-gp, which may likely be useful for sensitive and specific flow cytometric determination of MRP activity in clinical samples.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Multidrug resistance analysis in lymphoproliferative disease of large granular lymphocytes.

Multi-drug resistance (MDR) phenotype contributes to the ineffectiveness of chemotherapy. P-glycoprotein (PgP) and lung resistance protein (LRP) are proteins implicated in chemoresistance. We analysed the expression of PgP and LRP respectively in 17 and 15 cases of lymphoproliferative disease of granular lymphocytes (LDGL) including 10 cases of clonal large granular lymphocytic (LGL) leukaemia, six cases of oligoclonal (n = 5) and polyclonal (n = 1) CD3+ lymphoproliferation and one case of CD3- NK lymphocytosis. Functional PgP activity, as determined by Rh123 dye efflux assay, was found in all the patients. The mean percentage of effluxing cells was 47 +/- 22%, compared to 35 +/- 8% on normal lymphocytes (P<0.04). The efflux was blocked in the presence of verapamil, a PgP revertant agent. A high proportion of CD57+ cells (66 +/- 10%) from these patients expelled Rh123. Functional PgP activity was associated with expression of MDR1 mRNA. By using immunocytochemistry, LRP expression was detected in 11/15 patients (73%). 7/10 LGL leukaemia patients presented a LRP+/Efflux+ phenotype and 5/7 had LRP+/Efflux+/MDR1 mRNA+ phenotype. These findings suggest that the PgP+/LRP+ phenotype is frequently observed in LDGL. Its clinical relevance in aggressive cases remains to be determined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Loss of HLA molecules in B lymphomas is associated with an aggressive clinical course.

Major histocompatibility complex class I molecule expression is reduced in some malignant tumours permitting escape from immune surveillance and is therefore associated with a poor prognosis. Seven cases of non-Hodgkin lymphomas out of 300 cases of malignant lymphoproliferative disorders totally lacked expression of class I molecules as determined by flow cytometry. Clinical data confirmed a particular aggressiveness of these cases with frequent extra-nodal involvement, a poor international prognostic index, a histological high grade and a poor outcome leading to early death in five of the seven cases. A previous diagnosis of follicular lymphoma characterized by bcl-2 rearrangements was made in four of these cases. HLA-G (class Ib gene), which is reported to bind killer inhibitory receptors on NK cells, was absent from the cell surface. However, it was detected in three out of four cases at the mRNA level with transcripts encoding soluble forms. Additional analysis revealed other abnormalities: class II was negative in four out of the seven NHL cases and decreased expression of beta2 microglobulin was observed in all cases. Peptide transporter proteins (TAP1) were detected in various degrees by immunocytochemistry. These observations showed that total lack of class I or class II molecules is a rare event in NHL and is associated with a poor prognosis. This could support a role for specific autologous T cells in immune surveillance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Differential expression and activity of P-glycoprotein and multidrug resistance-associated protein in CD34-positive KG1a leukemic cells.

CD34+ acute myeloid leukemias generally respond poorly to chemotherapy when compared to CD34- myeloid leukemias. In order to contribute to the analysis of the mechanisms involved in this drug resistance, expression and activity of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP), two drug efflux pumps conferring multidrug resistance, have been investigated in the CD34+ KG1a leukemic myeloid cell line and in two CD34- K562 and HL60 leukemic myeloid cell lines. Reverse transcription-polymerase chain reaction and dye efflux assays revealed that KG1a cells express P-gp but not MRP whereas neither P-gp nor MRP were detected in K562 and HL60 cells. In addition, KG1a cells were demonstrated to display resistance to anticancer drug substrates for P-gp such as vincristine and daunorubicin and to poorly accumulate vincristine. These results indicated that P-gp, in contrast to MRP, is expressed and functional in the drug-resistant CD34+ KG1a cell line, that may constitute a useful cellular model to analyze the constitutive chemoresistance of CD34+ acute myeloid leukemias.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Inapparent polycythemia vera: an unrecognized diagnosis.

PURPOSE: The Polycythemia Vera Study Group (PVSG) has established useful criteria for the diagnosis of polycythemia vera. In some circumstances, an increase of plasma volume (PV) masks that of red cell mass (RCM), with hemoglobin (Hb) and hematocrit (Ht) remaining normal. This defines the concept of inapparent polycythemia. PATIENTS AND METHODS: One hundred and three patients seen in the hematology unit with the diagnosis of polycythemia vera were studied. There were 55 males and 48 females with a median age of 59 years. Ninety-five patients fulfilled the PVSG criteria. Spontaneous erythroid colonies and low serum erythropoietin level confirmed the diagnosis in the 8 other cases. Patients were classified according to Hb and Ht level. RESULTS: Group A consisted of 85 patients with increased Hb and Ht defined, respectively, by Hb > 18 g/dl, Ht > 0.52 in males and Hb > 16 g/dL, Ht>0.47 in females. Group B included 18 patients (17%) with inapparent polycythemia vera (IPV) defined by a normal Hb and Ht value at diagnosis. In this group, the reasons to perform RCM were as follows: splenomegaly associated with increased platelets and/or leucocytes counts (n = 8), portal vein thrombosis (n = 5), increased platelets or leucocytes counts without splenomegaly (n = 3), and isolated splenomegaly (n = 2). The two groups were balanced in terms of age, sex, leucocyte, serum iron, and platelet level. Hemoglobin and Ht levels were significantly different between the two groups. The difference between the PV was indeed highly significant. The mean PV increase was + 9.5% (nL < +20%) in group A versus + 36.3% in group B (P < 0.00005). Red cell mass was not different between the two groups. CONCLUSIONS: Increased Hb or Ht should constitute the sole criteria for RCM determination. In the context of portal vein thrombosis, isolated hyperleucocytosis, thrombocytosis, or splenomegaly, a RCM should be performed. The frequency of IPV remains to be specified but the diagnosis of polycythemia vera is probably underestimated.

Adult↗
PubMed1997

Multicentric evaluation of the MDR phenotype in leukemia. French Network of the Drug Resistance Intergroup, and Drug Resistance Network of Assistance Publique-Hôpitaux de Paris.

The wide discrepancies in the frequency of 'positive' samples for multidrug resistance (MDR) phenotype within the same type of tumor observed in the literature justified the need for the definition of consensus recommendations. To define standard techniques of MDR phenotype measurement, we ran a large multicentric evaluation of the different methods available. Thirty-six French centers participated in the study, and 742 samples of 2-10 x 10(6) viable cells were sent by overnight express mail between December 1993 and February 1996. The same batches of MRK16, 4E3 and UIC2 were used. Nineteen samples of leukemia (12 AML, 1 ALL, 6 lymphoproliferative syndromes) and six leukemic cell lines with different levels of MDR expression were tested. Five meetings reached agreement concerning the guidelines for each technique, except immunocytochemistry. The 19 fresh samples were tested by each center using one to four techniques among cytofluorometry, immunocytochemistry, functional tests and RT-PCR. Five samples were diagnosed as 'negative' according to local criteria, with few discordant results (0 to 16% of 'positive' results). For all the 14 remaining samples, large discrepancies were observed from center to center, and from one technique to another. No correlations could be found between techniques. Flow cytometric analysis of cells already exposed to MRK16 or control IgG2A, fixed in paraformaldehyde and sent to centers did not reduce the discrepancies between centers in two of the four samples with moderate expression, emphasizing the role of histogram interpretation. The use of alternative monoclonal antibodies (4E3 and UIC2) did not reduce the discrepancies observed. In a second step, the K562 parental cell line, a low resistant subline (K562/HHT100, x7 resistance index to DNR) and a high resistant subline (K562/HHT300, x125 resistance index to DNR) were sent blindly three times, with an increasing level of recommendations for flow cytometry. Dramatic improvements were observed in cytometric results when the result was expressed as the ratio of arithmetic mean of fluorescence of antibody (10 microg of MRK16)/arithmetic mean of fluorescence of control (10 microg IgG2A): the proportion of expected results increased from 61 to 100% for K562, and from 37 to 85% for K562/HHT100. For uptake and drug efflux measurements, the use of 1 h uptake of 0.1 microM of rhodamine, followed by 1 h efflux +/-10 microM of verapamil, permitted an increased reproducibility of the technique from 71 to 100% for K562 and K562/HHT100. Whatever the technique used, concordant results were obtained for K562/HHT300. The immunocytochemistry, using several antibodies (MRK16, JSB1 and C219) gave many non-interpretable results (44%), due to a frequent high background and discordant results between antibodies in the same centers, and discordant conclusions between centers. The group does not recommend this technique for circulating tumoral cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

CpG methylation patterns in the 5' part of the nonclassical HLA-G gene in peripheral blood CD34+ cells and CD2+ lymphocytes.

A dominant goal of research focused on the nonclassical human leukocyte antigen G (HLA-G) gene is to understand the molecular mechanism involved in its limited expression. In the present report, we examined DNA methylation as a potential regulatory mechanism of HLA-G transcription in two cell types of the adult lymphomyeloid lineage: CD2+ lymphocytes express several mRNA isoforms while transcripts are undetectable in CD34+ hematopoietic cells. The methylation status of 63 CpG sites in the promoter and in the 5' CpG island was established using bisulfite-treated genomic DNA sequencing. Methylation was first analyzed by the direct sequencing of bisulfite-treated and amplified products. The general patterns of CpG methylation in the 5' part of the gene were found to be similar for CD34+ cells and CD2+ lymphocytes: the distribution of methylation was not uniform across the 63 CpG sites. In the promoter region, both CpG dinucleotides were partially or fully methylated whereas in the CpG island, several CpG sites were totally demethylated. Unexpectedly, in HLA-G positive CD2+ lymphocytes, a great number of CpG dinucleotides displayed a higher frequency of methylation relative to that found in CD34+ cells. However, the sequence analysis of cloned products revealed that the molecules have different methylation patterns which suggests that the HLA-G gene is differentially expressed in CD2+ cells. Our results suggest that methylation is not the sole mechanism that achieves the repression of HLA-G transcription in immature CD34+ cells.

Adult↗
PubMed1996

Inhibition of P-glycoprotein activity in human leukemic cells by mifepristone.

The antiprogestatin drug mifepristone has previously been shown to potentiate anti-cancer drug activity in rodent multidrug-resistant cell lines through inhibition of P-glycoprotein (P-gp) function. In order to characterize P-gp-mifepristone interactions in human tumoral cells, we have studied the effect of the antiprogestatin agent on P-gp activity in human CD34+ leukemic cells known to display high levels of P-gp-related drug efflux. P-gp-mediated transport of the fluorescent dye rhodamine 123 occurring in the CD34+ KG1a myeloid leukemia cell line was found to be strongly inhibited by mifepristone in a dose-dependent manner. Similarly to verapamil, a well-known chemosensitizer agent, the antiprogestatin drug increased doxorubicin cytotoxicity in KG1a cells. Mifepristone, when used at a 10 microM concentration thought to be achievable in vivo without major toxicity, was also able to markedly decrease cellular rhodamine 123 efflux occurring in CD34+ blast cells isolated from six patients suffering from myeloid acute leukemias. These results thus indicate that mifepristone can strongly inhibit P-gp activity in human cells, including tumoral cells freshly isolated from patients, therefore suggesting that the clinical use of this compound may contribute to down-modulate P-gp-mediated drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Internalization of human macrophage surface antigens induced by monoclonal antibodies.

Drugs intended to be endocytosed by macrophages may be transported by MAbs directed against these cells. Twenty MAbs were investigated for this purpose. The binding of these MAbs to macrophages obtained from a 7 day culture of blood monocytes showed that anti-CD11b and anti-CD14 recognized the highest number of cell surface antigen sites. Further assays determined that anti-CD63, Mo5 and anti-CD33 were the MAbs that induced the strongest modulation of the corresponding antigens, the highest rate being with anti-CD63. Endocytosis of antigen-antibody complexes was evidenced by the presence of MAbs in the cytoplasm. Anti-CD63 MAbs induced the highest internalization in this assay. For most MAbs, however, the density of antigen sites and the intensity of antigen modulation were not predictive of the amount of MAb detected in the cytoplasm.

Antibodies, Monoclonal↗
PubMed1995

Quantification and molecular analysis of plasmatic HLA-BCw molecules with a locus B and Cw HLA specific mAb (B1.23.2 mAb).

Plasmatic HLA class I molecules were analysed quantitatively and qualitatively with a B and Cw locus-specific mAb, B1.23.2. sHLA-BCw were detected among all individuals with a wide range of concentration. The HLA-A29(19) allele was significantly associated with an increased sHLA-BCw mean concentration. Three different isoforms of relative molecular weights of 44, 39 and 36kDa were detected. The 39 kDa class I heavy chain was not detected after immunoprecipitation with mAb B1.23.2 in 17% of tested plasma, but was immunoprecipitated with W6/32 mAb.

Alleles↗