Hematologie biologique

Paris, France

Hematologie biologique

Paris, France

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Nguyen-Khac F.,Hematologie biologique | Nguyen-Khac F.,University Pierre and Marie Curie | Lesty C.,Hematologie biologique | Eclache V.,University of Paris 13 | And 18 more authors.
Genes Chromosomes and Cancer | Year: 2010

Evolution to myelofibrosis (MF), acute myeloid leukemia or myelodysplastic syndrome (AML/MDS) may occur over time in myeloproliferative neoplasms (MPN) patients most likely due to the acquisition of additional mutations. The Groupe Francophone de cytogenetique hematologique (GFCH) has collected and reviewed 82 patients with transformation of MPN (66 AML/MDS and 16 MF). JAK2V617F and TET2 mutations were searched for in 40 and 32 patients, respectively. Significantly more 7/del(7q) (P = 0.004) and 5/del(5q) (P = 0.03) were found in AML/MDS with a higher incidence of dup1q (P = 0.01) in MF. Some specific chromosomal abnormalities occurred together, for example 5/del(5q) and 17/del(17p) (P = 0.0007). In multivariate analysis, two factors were independently associated with an inferior overall survival (OS); AML/MDS transformation (P < 0.0001) and 5/del(5q) abnormality (P = 0.02). Although both giving rise to loss of 7q, der(1;7) differed from other 7q deletions in terms of distribution (lower frequency of AML/MDS, P = 0.02), association with chromosomal abnormalities (absence of 5/del(5q), P = 0.003; increased del(20q), P = 0.05), and longer OS (P = 0.0007). We detected 24/40 (60%) JAK2V617F and 8/25 (32%) TET2 mutations in samples following transformation, ranging from wild-type to mutated forms of both genes. The mutated and wild-type forms of the genes were not found to be associated with a specific chromosomal abnormality. There was no evidence that JAK2 or TET2 mutations were associated with the type of MPN transformation, whereas the type of cytogenetic abnormalities were strongly linked, perhaps indicating that they play a specific role in the transformation process. © 2010 Wiley-Liss, Inc.


Cuccuini W.,Hematologie Biologique | Cuccuini W.,Institut Universitaire de France | Briere J.,Institut Universitaire de France | Briere J.,French Institute of Health and Medical Research | And 16 more authors.
Blood | Year: 2012

Approximately 5-10% of diffuse large Bcell lymphomas (DLBCL) harbor a 8q24/MYC rearrangement (MYC +). We determined the prognostic significance of MYC rearrangement in patients with relapsed/refractory DLBCL prospectively treated by R-ICE or R-DHAP followed by highdose therapy and autologous stem cell transplantation. Twenty-eight (17%) of the 161 patients analyzed presented a MYC +rearrangement, targeted as either simple hit (25%) or complex hits (n=75%) including MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6. Results were statistically highly concordant in matched primary and relapsed biopsies (n = 45). Compared to the MYC - DLBCL patients, the MYC - DLBCL patients presented with a more elevated lactico- deshydrogenase level (P = .0006) and a more advanced age adjusted international prognostic index (P = .0039). The 4-year PFS and OS were significantly lower in the MYC +DLBCL patients than those in the MYC -DLBCL patients, with rates of 18% vs 42% (P = .0322), and of 29% vs 62% (P = .0113), respectively. Type of treatment, R-DHAP or R-ICE, had no impact on survivals, with 4-year PFS rates of 17% vs 19% and 4-year OS rates of 26% vs 31%. In conclusion, MYC rearrangement is an early event in DLBCL. MYC + DLBCL patients have a significant inferior prognosis than MYC - DLBCL patients. Their outcome was not influenced by the proposed salvage therapy. © 2012 by The American Society of Hematology.


Manceau S.,University of Paris Descartes | Manceau S.,Groupe Hospitalier Cochin Saint Vincent Of Paul | Giraud C.,University of Paris Descartes | Giraud C.,Groupe Hospitalier Cochin Saint Vincent Of Paul | And 11 more authors.
International Journal of Pharmaceutics | Year: 2010

The efficacy of drugs acting within lymphocytes depends on their intracellular concentrations, which could be modulated by membrane efflux transporters including P-glycoprotein (P-gp), encoded by the MDR1 gene. In particular, P-gp induction may compromise the efficacy of its substrates. Rifampicin and phenobarbital have been shown to induce P-gp in hepatic and intestinal cells through the activation of the nuclear receptors PXR and CAR. However, controversial data exist in human lymphocytes. We investigated the effect of these drugs on P-gp activity and expression in lymphocytes in vitro and ex vivo. CCRF-CEM cells and peripheral blood mononuclear cells (PBMCs) from healthy volunteers were incubated in the presence of rifampicin, phenobarbital, or without any drug. P-gp activity was measured by flow cytometry using DiOC6 efflux. MDR1, PXR and CAR mRNA expression were measured by quantitative RT-PCR. Neither P-gp activity nor MDR1 mRNA expression were modified by rifampicin or phenobarbital both in CCRF-CEM cells and PBMCs. Moreover, P-gp protein expression at the membrane was neither detectable nor induced. The very weak PXR and CAR mRNA expression levels in these cells could partly explain these results. Therefore, P-gp induction by rifampicin and phenobarbital may play a negligible role in drug interactions occurring within lymphocytes. © 2010 Elsevier B.V.


Ciesla M.,Jagiellonian University | Wypasek E.,Jagiellonian University | Corral J.,University of Murcia | Alhenc-Gelas M.,Hematologie Biologique | Undas A.,Jagiellonian University
Blood Coagulation and Fibrinolysis | Year: 2015

Type I antithrombin deficiency is an autosomal dominant disorder associated with thromboembolic complications mainly related to single-point mutations in SERPINC1, the gene encoding antithrombin. Chromosomal rearrangements have been found in up to 10% of cases with type I antithrombin deficiency. We report here the first heterozygous deletion of SERPINC1 exon 1 identified in a 44-year-old man with type I deficiency who developed deep vein thrombosis of the left leg complicated by pulmonary embolism. This study demonstrates that the search for large gene rearrangements in SERPINC1 can be a useful diagnostic approach, particularly in patients with type I antithrombin deficiency without mutations in SERPINC1. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Wypasek E.,Jagiellonian University | Potaczek D.P.,Jagiellonian University | Alhenc-Gelas M.,Hematologie Biologique | Undas A.,Jagiellonian University
Blood Coagulation and Fibrinolysis | Year: 2014

Protein S is one of the major natural anticoagulants. A missense serine 501 to proline (S501P) Heerlen polymorphism is associated with reduced levels of free protein S. Heerlen polymorphism, especially when combined with other thrombophilia risk factors, can lead to thromboembolic complications. To our knowledge, we report here the first Polish case associated with heterozygous Heerlen polymorphism resulting in type III protein S deficiency, detected in a 50-year-old man with several thrombotic episodes of deep and superficial veins and a highly positive thrombotic family history. The patient also had factor V Leiden mutation and persistently elevated anticardiolipin antibodies. It seems that increased risk of thrombotic complications could be explained in the patient by a synergy between the effects of Heerlen polymorphism, factor V Leiden heterozygous status and antiphospholipid syndrome. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Alhenc-Gelas M.,Hematologie biologique | Alhenc-Gelas M.,French Institute of Health and Medical Research | Canonico M.,French Institute of Health and Medical Research | Morange P.E.,French Institute of Health and Medical Research | And 2 more authors.
Journal of Thrombosis and Haemostasis | Year: 2010

Background:-Only a few mutations associated with qualitative protein S deficiency have already been described. Sensitivity and specificity for type II PROS1 mutations of commercially available reagents for measuring Protein S (PS) activity are not well established. Whether these mutations are significant risk factors for thrombosis remains an unresolved question. Methods:-In order to address the first point, we present and discuss the results of PROS1 analysis performed in the 30 probands with type II PS-inherited deficiency suspicion and 35 relatives, studied in our laboratory between 2000 and 2008. In order to investigate the influence of type II mutations on the coagulability level, thrombin generation tests were performed on plasma from 102 PROS1 type II, type I/III or PS Herleen mutation heterozygous carriers and controls. Results:-Mutations (12 novel, six already described) which probably explain the qualitative phenotype, were found in 27 (90%) out of the 30 probands studied. In relatives, 78% of heterozygotes presented with a type II phenotype. An APC resistance phenotype was documented in type II and type I/III defects heterozygous carriers; however, the effect of type II was milder than the effect of type I/III PS mutations. Conclusions: A PS functional assay (Staclot PS, Stago) was efficient in screening for PROS1 type II defects, particularly in probands. A significant positive influence of type II mutations on ex vivo thrombin generation was demonstrated. However, whether these mutations increase the risk of venous thromboembolism requires further investigation. © 2010 International Society on Thrombosis and Haemostasis.


PubMed | CHU Rouen, Hematologie biologique and Pharmacovigilance
Type: Case Reports | Journal: La Revue de medecine interne | Year: 2015

While in most countries warfarin is the preferred anti-vitaminK, fluindione, a molecule with a prolonged half-life remains largely prescribed in France. Some of its side effects, including immuno-allergic complications, remain poorly understood.A 77-year-old woman presented with a febrile severe neutropenia of immunoallergic mechanism with a favourable outcome associated with fluindione, introduced 25days earlier for the treatment of atrial fibrillation.This rare side effect is a reminder of the importance of biological monitoring in the first weeks following the introduction of fluindione and key diagnostic elements and therapeutic aspects of iatrogenic agranulocytosis.


PubMed | Hematologie biologique
Type: Journal Article | Journal: Journal of thrombosis and haemostasis : JTH | Year: 2010

Only a few mutations associated with qualitative protein S deficiency have already been described. Sensitivity and specificity for type II PROS1 mutations of commercially available reagents for measuring Protein S (PS) activity are not well established. Whether these mutations are significant risk factors for thrombosis remains an unresolved question.In order to address the first point, we present and discuss the results of PROS1 analysis performed in the 30 probands with type II PS-inherited deficiency suspicion and 35 relatives, studied in our laboratory between 2000 and 2008. In order to investigate the influence of type II mutations on the coagulability level, thrombin generation tests were performed on plasma from 102 PROS1 type II, type I/III or PS Herleen mutation heterozygous carriers and controls.Mutations (12 novel, six already described) which probably explain the qualitative phenotype, were found in 27 (90%) out of the 30 probands studied. In relatives, 78% of heterozygotes presented with a type II phenotype. An APC resistance phenotype was documented in type II and type I/III defects heterozygous carriers; however, the effect of type II was milder than the effect of type I/III PS mutations.A PS functional assay (Staclot PS, Stago) was efficient in screening for PROS1 type II defects, particularly in probands. A significant positive influence of type II mutations on ex vivo thrombin generation was demonstrated. However, whether these mutations increase the risk of venous thromboembolism requires further investigation.


Approximately 5-10% of diffuse large B-cell lymphomas (DLBCL) harbor a 8q24/MYC rearrangement (MYC(+)). We determined the prognostic significance of MYC rearrangement in patients with relapsed/refractory DLBCL prospectively treated by R-ICE or R-DHAP followed by high-dose therapy and autologous stem cell transplantation. Twenty-eight (17%) of the 161 patients analyzed presented a MYC(+) rearrangement, targeted as either simple hit (25%) or complex hits (n=75%) including MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6. Results were statistically highly concordant in matched primary and relapsed biopsies (n = 45). Compared to the MYC(-) DLBCL patients, the MYC(+) DLBCL patients presented with a more elevated lactico-deshydrogenase level (P = .0006) and a more advanced age adjusted international prognostic index (P = .0039). The 4-year PFS and OS were significantly lower in the MYC(+) DLBCL patients than those in the MYC(-) DLBCL patients, with rates of 18% vs 42% (P = .0322), and of 29% vs 62% (P = .0113), respectively. Type of treatment, R-DHAP or R-ICE, had no impact on survivals, with 4-year PFS rates of 17% vs 19% and 4-year OS rates of 26% vs 31%. In conclusion, MYC rearrangement is an early event in DLBCL. MYC(+) DLBCL patients have a significant inferior prognosis than MYC(-) DLBCL patients. Their outcome was not influenced by the proposed salvage therapy.


PubMed | Laboratoire hemato biologie, Caen University Hospital Center, Service dhematologie biologique, Toulouse University Hospital Center and 4 more.
Type: Journal Article | Journal: Annales de biologie clinique | Year: 2014

The full blood count (FBC) is the most prescribed laboratory test in France. Due to the lack of data, there is a great variability in reference values of the FBC, between medical laboratories. The aim of this work was to provide normal reference values for FBC in adults. These normal values were defined in a population of 33 258 healthy adults, 19 612 men and 13 646 women. These values were determined after excluding subjects having conditions in order to modify, either directly or indirectly, FBC parameters. For each parameter, we provide results for values of standard parameters, by sex and age, from 16 to 69 years. In addition, we present FBC values from a population of 339 subjects aged over 69 years with no comorbidities. These normal values are proposed to be used in everyday practice. They make it possible to distinguish, without ambiguity, a normal situation from a pathological situation. Moreover, they can be applied to the entire metropolitan France.

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