Laboratoire dHematologie

Dreuil-lès-Amiens, France

Laboratoire dHematologie

Dreuil-lès-Amiens, France
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Morel P.,Service Route | Morel P.,University of Lille Nord de France | Duhamel A.,University of Lille Nord de France | Hivert B.,Service Route | And 4 more authors.
Blood | Year: 2010

The median survival of patients with primary myelofibrosis ranges from 3.5 to 5.5 years, and most patients die from cause related to the disease, including blast phase (BP, in 5%-30% of cases). Because identification of high-risk patients might use information collected during the clinical course, we assessed the prognostic value of time-dependent covariates for 2 competing risks (death and BP) in a series of 172 patients. Significant (P < .01) adverse time-dependent prognostic factors for the risk of death were the time to onset of anemia (hemoglobin < 100 g/L [10 g/dL]), leukocytosis (leukocyte count > 30 × 109/L), thrombocytopenia (platelet count < 150 × 109/L), presence of circulating blasts, intermediate-high or high International Working Group for Myelofibrosis Research and Treatment score, and time to splenectomy. The first 3 dependent covariates and the time to chemotherapy initiation (P = .05) were prognostic factors for the risk of BP. The prognostic effect of onset of leukocytosis was significantly more pronounced for BP than for death. Thus, occurrence during the follow-up of characteristics associated with an adverse prognostic value at diagnosis also influenced the risks of death and BP. Patients with leukocytosis should be closely monitored. These data might efficiently help to evaluate the severity of the disease before treatment decision during the clinical course. © 2010 by The American Society of Hematology.

Donadieu J.,Service dHemato Oncologie Pediatrique Registre des Neutropenies Congenitales | Fenneteau O.,Laboratoire dHematologie | Beaupain B.,Service dHemato Oncologie Pediatrique Registre des Neutropenies Congenitales | Chantelot C.B.,University Pierre and Marie Curie
Orphanet Journal of Rare Diseases | Year: 2011

The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe (<0.5 G/l) or mild (between 0.5-1.5 G/l), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections, acute gingivostomatitis and chronic parodontal disease, and each successive infection may leave permanent sequelae. The risk of infection is roughly inversely proportional to the circulating polymorphonuclear neutrophil count and is particularly high at counts below 0.2 G/l. When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia) and congenital forms that may either be isolated or part of a complex genetic disease. Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant. About half the forms of congenital neutropenia with no extra-hematopoetic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE) mutations. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia. Congenital neutropenia may also be associated with a wide range of organ dysfunctions, as for example in Shwachman-Diamond syndrome (associated with pancreatic insufficiency) and glycogen storage disease type Ib (associated with a glycogen storage syndrome). So far, the molecular bases of 12 neutropenic disorders have been identified. Treatment of severe chronic neutropenia should focus on prevention of infections. It includes antimicrobial prophylaxis, generally with trimethoprim-sulfamethoxazole, and also granulocyte-colony-stimulating factor (G-CSF). G-CSF has considerably improved these patients' outlook. It is usually well tolerated, but potential adverse effects include thrombocytopenia, glomerulonephritis, vasculitis and osteoporosis. Long-term treatment with G-CSF, especially at high doses, augments the spontaneous risk of leukemia in patients with congenital neutropenia. © 2011 Donadieu et al; licensee BioMed Central Ltd.

Itzykson R.,University of Paris 13 | Kosmider O.,Service dHematologie Biologique | Cluzeau T.,Nice University Hospital Center | Mansat-De Mas V.,Toulouse University Hospital Center | And 10 more authors.
Leukemia | Year: 2011

The impact of ten-eleven-translocation 2 (TET2) mutations on response to azacitidine (AZA) in MDS has not been reported. We sequenced the TET2 gene in 86 MDS and acute myeloid leukemia (AML) with 20-30% blasts treated by AZA, that is disease categories wherein this drug is approved by Food and Drug Administration (FDA). Thirteen patients (15%) carried TET2 mutations. Patients with mutated and wild-type (WT) TET2 had mostly comparable pretreatment characteristics, except for lower hemoglobin, better cytogenetic risk and longer MDS duration before AZA in TET2 mutated patients (P0.03, P0.047 and P0.048, respectively). The response rate (including hematological improvement) was 82% in MUT versus 45% in WT patients (P0.007). Mutated TET2 (P0.04) and favorable cytogenetic risk (intermediate risk: P0.04, poor risk: P0.048 compared with good risk) independently predicted a higher response rate. Response duration and overall survival were, however, comparable in the MUT and WT groups. In higher risk MDS and AML with low blast count, TET2 status may be a genetic predictor of response to AZA, independently of karyotype. © 2011 Macmillan Publishers Limited All rights reserved.

Chien W.W.,University Claude Bernard Lyon 1 | Domenech C.,University Claude Bernard Lyon 1 | Catallo R.,University Claude Bernard Lyon 1 | Kaddar T.,University Claude Bernard Lyon 1 | And 5 more authors.
Oncogene | Year: 2011

The p16INK4a protein regulates cell cycle progression mainly by inhibiting the activity of G1-phase cyclin-dependent kinases (CDKs) 4 and 6, the subsequent retinoblastoma protein (pRb) phosphorylation and E2F transcription factor release. The p16INK4a protein can also repress the activity of other transcription factors, such as c-myc, nuclear factor-kappaB and c-Jun/AP1. Here, we report that, in two p16-/-, pRbWT and p53WT cell lines (MCF7 and U87), p16INK4a overexpression induces a dramatic decrease in CDK1 protein expression. In response to p16 INK4a, the decreased rate of CDK1 protein synthesis, its unchanged protein half-life, unreduced CDK1 mRNA steady-state levels and mRNA half-life allow us to hypothesize that p16 INK4a could regulate CDK1 expression at the post-transcriptional level. This CDK1 downregulation is mediated by the 3′-untranslated region (3′UTR) of CDK1 mRNA as shown by translational inhibition in luciferase assays and is associated with a modified expression balance of microRNAs (miRNAs) that potentially regulate CDK1, analyzed by TaqMan Human microRNA Array. The p16INK4a-induced expression of two miRNAs (miR-410 and miR-650 chosen as an example) in MCF7 cells is confirmed by individual reverse transcription-qPCR. Furthermore, we show the interaction of miR-410 or miR-650 with CDK1-3′UTR by luciferase assays. Endogenous CDK1 expression decreases upon both miRNA overexpression and increases with their simultaneous inhibition. The induction of miR-410, but not miR-650 could be related to the pRb/E2F pathway. These results demonstrate the post-transcriptional inhibition of CDK1 by p16INK4a. We suggest that p16INK4a may regulate gene expression by modifying the functional equilibrium of transcription factors and consequently the expression balance of miRNAs. © 2011 Macmillan Publishers Limited All rights reserved.

Gibot S.,Reanimation Medicale | Gibot S.,University of Lorraine | Bene M.C.,University of Lorraine | Noel R.,Reanimation Medicale | And 9 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2012

Rationale: Although the outcome of sepsis benefits from the prompt administration of appropriate antibiotics on correct diagnosis, the assessment of infection in critically ill patients is often a challenge for clinicians. In this setting, simple biomarkers, especially when used in combination, could prove useful. Objectives: To determine the usefulness of combination biomarkers to diagnose sepsis. Methods: Three hundred consecutive patients were enrolled to construct a biologic score that was next validated in an independent prospective cohort of 79 critically ill patients from another center. Measurement and Main Results: Plasma concentrations of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and procalcitonin (PCT) were assayed, and the expression of the high-affinity immunoglobulin-Fc fragment receptor I (FcgRI) CD64 on neutrophils (polymorphonuclear [PMN] CD64 index) in flow cytometry was measured. A "bioscore" combining these biomarkers was constructed. Serum concentrations of PCT and sTREM-1 and the PMN CD64 index were higher in patients with sepsis compared with all others (P < 0.001 for the three markers). These biomarkers were all independent predictors of infection, the best receiver-operating characteristic curve being obtained for the PMN CD64 index. The performance of the bioscore, better than that of each individual biomarker, was externally confirmed in the validation cohort. Conclusions: This prospective study, including inceptive and validation cohorts of unselected intensive care unit patients, demonstrates the high performance of a bioscore combining the PMNCD64 index together with PCT and sTREM-1 serum levels in diagnosing sepsis in the critically ill patient. Copyright © 2012 by the American Thoracic Society.

Sarlon-Bartoli G.,Aix - Marseille University | Bennis Y.,Aix - Marseille University | Lacroix R.,Aix - Marseille University | Lacroix R.,Laboratoire DHematologie | And 14 more authors.
Journal of the American College of Cardiology | Year: 2013

Objectives This study sought to analyze whether the plasmatic level of leukocyte-derived microparticles (LMP) is associated with unstable plaques in patients with high-grade carotid stenosis. Background Preventive carotid surgery in asymptomatic patients is currently debated given the improvement of medical therapy. Therefore, noninvasive biomarkers that can predict plaque instability are needed. The LMPs, originating from activated or apoptotic leukocytes, are the major microparticle (MP) subset in human carotid plaque extracts. Methods Forty-two patients with >70% carotid stenosis were enrolled. Using a new standardized high-sensitivity flow cytometry assay, LMPs were measured before thromboendarterectomy. The removed plaques were characterized as stable or unstable using histological analysis according to the American Heart Association criteria. The LMP levels were analyzed according to the plaque morphology. Results The median LMP levels were significantly higher in patients with unstable plaque (n = 28; CD11bCD66b+ MP/μl 240 [25th to 75th percentile: 147 to 394], and CD15+ MP/μl 147 [60 to 335]) compared to patients with stable plaque (16 [0 to 234] and 55 [36 to 157]; p < 0.001 and p < 0.01, respectively). The increase in LMP levels was also significant when considering only the group of asymptomatic patients with unstable plaque (n = 10; CD11bCD66b+ MP/μl 199 [153 to 410] and CD15+ MP/μl 78 [56 to 258] compared with patients with stable plaque (n = 14; 20 [0 to 251] and 55 [34 to 102]; p < 0.05 and p < 0.05, respectively). After logistic regression, the neurologic symptoms (odds ratio: 48.7, 95% confidence interval: 3.0 to 788, p < 0.01) and the level of CD11bCD66b+ MPs (odds ratio: 24.4, 95% confidence interval: 2.4 to 245, p < 0.01) independently predicted plaque instability. Conclusions LMP constitute a promising biomarker associated with plaque vulnerability in patients with high-grade carotid stenosis. These data provide clues for identifying asymptomatic subjects that are most at risk of neurologic events. © 2013 by the American College of Cardiology Foundation Published by Elsevier Inc.

Lhermusier T.,University Paul Sabatier | Chap H.,University Paul Sabatier | Payrastre B.,University Paul Sabatier | Payrastre B.,Laboratoire dHematologie
Journal of Thrombosis and Haemostasis | Year: 2011

Like all eukaryotic cells, platelets maintain plasma membrane phospholipid asymmetry in normal blood circulation via lipid transporters, which control transbilayer movement. Upon platelet activation, the asymmetric orientation of membrane phospholipids is rapidly disrupted, resulting in a calcium-dependent exposure of the anionic phospholipid, phosphatidylserine (PS), at the outer platelet surface. This newly-exposed PS surface is a major component of normal hemostasis because it supports platelet procoagulant function. Binding of blood clotting enzyme complexes to this negatively-charged membrane surface allows a dramatic increase in the rate of conversion of zymogens to active serine proteases, which in turn produce a burst of thrombin leading to the formation of a fibrin clot and further platelet activation. Cells have the capacity to catalyze transbilayer phospholipid exchange via ATP-requiring translocase enzymes (flippases and floppases), which control unidirectional phospholipid transport against a concentration gradient. They also use an energy-independent, calcium-dependent scramblase activity to govern the bidirectional exchange of phospholipids between the two leaflets of the bilayer; this activity is essential for PS exposure during platelet activation. Scramblase activity, biochemically characterized in the 1980s, is deficient in patients with Scott syndrome, a rare inherited bleeding disorder with defective platelet procoagulant activity. Despite considerable efforts, the platelet scramblase protein remained elusive for years but a significant advance has recently been made with the identification of TMEM16F, a membrane protein essential for calcium-dependent PS exposure whose loss of function mutations are found in Scott syndrome. This review recalls historical aspects of platelet membrane asymmetry characterization, summarizes the mechanisms and roles of PS exposure following platelet activation and discusses the recent identification of TMEM16F and its significance in the scrambling process. © 2011 International Society on Thrombosis and Haemostasis.

Guermazi S.,Laboratoire dhematologie | Znazen R.,Laboratoire dhematologie
Pathologie Biologie | Year: 2011

Activated protein C resistance (APCR) is a coagulation abnormality often linked to FV Leiden mutation, a single nucleotide G1691A substitution resulting in arginine 506 → glutamine missense factor V mutation. FV Leiden has a frequency of 20 to 30% in groups of patients with venous thrombosis while it is of 4 to 10% in normal subjects. FV Leiden is considered as a weak risk factor of thrombosis except in homozygote. FV Leiden is implicated in deep venous thrombosis occurrence. Duration of oral anticoagulant treatment is six months in patients developing a first venous thrombosis except in patients with combined defects or a clinical context suggesting a high risk of severe relapse. Detection of APCR by coagulation methods is often used in first intention with a high specificity if plasmas tested are diluted in factor V deficient plasma. Genotyping study is essential to establish the heterozygote or homozygote statute and certain teams perform it directly. Nevertheless, APCR not related to FV Leiden could be an independent thrombosis risk factor. APCR and FV Leiden are included in laboratory investigations of thrombophilic markers in patients less than 50 years with venous thrombosis. In arterial thrombosis, FV Leiden implication is weak or absent. FV Leiden increases the risk of thrombosis in other situations as in patients with cancer. An association with recurrent miscarriages and other vasculoplacental complications is also reported in many studies but the data concerning the efficacy of antithrombotic treatment to prevent recurrence are currently insufficient. © 2009 Elsevier Masson SAS.

Marion S.,Laboratoire dHematologie
Revue Francophone des Laboratoires | Year: 2010

Practical experience in accreditation in Haematology The prerequisite for successful accreditation is to promote staff awareness of a brand new "work culture". The operational implementation phase is based on the application of a European reference standard (NF IN ISO 15189) and contributes to the creation of a quality management system as well as the formalization of our work practices. As a result, it is necessary to reconsider the structures and to define everyone's tasks precisely. This involves an ongoing improvement process, which consists in defining quality objectives, monitoring the system through internal or external audits, and launching corrective and preventive actions. Concurrently, technical skills are assessed, and they rely on the good control of the materials and methods employed (method validation, internal and external controls, and metrology). The successful implementation of such a procedure relies on a qualified and motivated personnel on both quality and technical levels. © 2010 - Elsevier Masson SAS - Tous droits réservés.

Ben Lassoued A.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Nivaggioni V.,Laboratoire dHematologie | Gabert J.,Laboratoire Of Biochimie Et Of Biologie Moleculaire | Gabert J.,French Institute of Health and Medical Research
Expert Review of Molecular Diagnostics | Year: 2014

Minimal residual disease (MRD) assays are of a great value to assess treatment efficacy and may provide prognostic information. This is particularly relevant in the era of targeted therapy where the introduction of MRD monitoring has fundamentally transformed the way in which cancer patients are managed. While MRD guidelines are well-established for chronic myeloid leukemia, acute promyelocytic leukemia and acute lymphoblastic leukemia, areas for continuing development are available. High level of standardization and regular external quality control rounds and recommendations for data interpretation remain essential to improve MRD monitoring. In this review, we describe the different applications of MRD assays in most frequent hematologic malignancies and solid cancer and provide an overview of the strengths and potential weaknesses of each method. © 2014 Informa UK, Ltd.

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