Philippe JEAN-PIERRE

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• Type de publi. : Article dans une revue
• Date de publi. : 03/01/2022
• Auteurs : Auriane BidautErwan FlécherNicolas NesselerKarl BounaderAndré VincentelliMouhammed MoussaClément DelmasJean PorterieKarine NubretMathieu PernotMichel KindoClément SchneiderPhilippe GaudardPhilippe RouvièreMagali MichelThomas SénageAude BoignardOlivier ChavanonConstance VerdonkMarylou ParaBaptiste MailleVlad GariboldiMatteo PozziElisabeth Hugon-ValletPierre-Yves LitzlerFrédéric AnselmeKatrien BlanchartGerard BabatasiMarie BielefeldSandrine GrosjeanCostin RaduDavid HamonThierry BourguignonThibaud GenetRomain EschalierNicolas D’ostrevyHélène NougueAnne Cécile MartinFabrice VanhuyseHugues BlangyChristophe LeclercqRaphaël P MartinsVincent Galand
• Organismes : Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011
• Publié dans Critical Care Medicine le 31/10/2020

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Résumé : OBJECTIVES: Temporary circulatory support (TCS) as a bridge-to-left ventricular assist device (BTL) in cardiogenic shock patients has been increasing, but limited data exists on this BTL strategy. We aimed at analyzing the outcome of BTL patients in a population of cardiogenic shock patients compared with those without TCS at the time of the left ventricular assist device (LVAD) surgery and identify predictors of postoperative mortality in this specific population. DESIGN: A multicenter retrospective observational study conducted in 19 centers from 2006 to 2016. SETTING: Nineteen French centers. PATIENTS: A total of 329 cardiogenic shock patients at the time of LVAD implantation were analyzed. Patients were divided in three groups: those under TCS at the time of LVAD implantation ( n = 173), those with TCS removal before LVAD surgery ( n = 24), and those who did not undergo a bridging strategy ( n = 152). Primary endpoint was 30-day mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the BTL group, 68 (39.3%), 18 (10.4%), and 15 (8.7%) patients were under venoarterial extracorporeal membrane oxygenation, Impella, and IABP support alone, and 72 patients (20.6%) were under multiple TCS support. BTL patients presented similar 30 days survival compared with the TCS removal and non-BTL groups. However, BTL group had a significantly longer ICU duration stay, with two-fold duration of mechanical ventilation time, but the three groups experienced similar postoperative complications. Multivariate analysis identified three independent predictors of mortality in the BTL group: combined surgery with LVAD, body mass index (BMI), and heart failure (HF) duration. BTL strategy was not an independent predictor of mortality in cardiogenic shock patients who underwent LVAD. CONCLUSIONS: BTL strategy is not associated with a lower survival among cardiogenic shock patients with LVAD implantation. Predictors of mortality are combined surgery with LVAD, higher BMI, and HF duration.

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• Type de publi. : Article dans une revue
• Date de publi. : 02/01/2022
• Auteurs : Noura ZahirPierre MagriWen LuoJean-Jacques GaumetPhilippe Pierrat
• Organismes : Laboratoire Lorrain de Chimie Moléculaire Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes Wuhan University of Technology Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes Laboratoire Lorrain de Chimie Moléculaire
• Publié dans ENERGY & ENVIRONMENTAL MATERIALS le 26/10/2020

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Résumé : Graphene quantum dots (GQDs) which are nano‐fragments of graphene with an average size between 2 to 50 nm have attracted much attention due to their outstanding properties such as high conductivity, high surface area and good solubility in various solvents. GQDs combine the quantum confinement and edges effects and the properties of graphene. Therefore, GQDs offers a broad range of applications in various fields (medicine, energy conversion and energy storage devices). This review will present the recent research based on the introduction of GQDs in batteries, supercapacitors and micro‐supercapacitors as electrodes materials or mixed with an active material as an auxiliary agent. Tables, discussed on selected examples, summarize the electrochemical performances and finally, challenges and perspectives are recalled for the subsequent optimization strategy of electrode materials. This review is expected to appeal a broad interest on functional GQDs materials and promote the further development of high‐performance energy storage device.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2022
• Auteurs : Françoise SchmittAurélien ScalabrePierre-Yves MureClaude BorrioneJean-Louis LemelleDyuti SharmaStéphan de NapoliSabine IrtanGuillaume LevardFrançois BecmeurPhilippe BuissonLaurent FourcadeAlexis ArnaudPhiline de VriesSophie BranchereauCynthia GarignonFrédérique SauvatN. KalfaHubert LardySandy Jochault-RitzEmmanuel SapinHélène CoridonMarc MargaryanMyriam PouzacLuana CarfagnaMarie-Laurence PolimerolFrançois VarletSabine SarnackiCélia CrétolleGuillaume Podevin
• Organismes : Centre Hospitalier Universitaire d'Angers Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Hôpital Femme Mère Enfant [CHU - HCL] Hospices Civils de Lyon Hôpital de la Timone [CHU - APHM] Centre Hospitalier Régional Universitaire de Nancy Centre Hospitalier Régional Universitaire [CHU Lille] Evaluation des technologies de santé et des pratiques médicales - ULR 2694 Centre Hospitalier Universitaire de Nantes = Nantes University Hospital CHU Trousseau [APHP] Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Centre Hospitalier Universitaire [Strasbourg] CHU Amiens-Picardie Service de Pédiatrie médicale [CHU Limoges] Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Centre Hospitalier Régional Universitaire de Brest Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre] Centre hospitalier de Saint-Brieuc [Hôpital Yves Le Foll] Hôpital Necker - Enfants Malades [AP-HP] Centre Hospitalier Régional Universitaire [Montpellier] Département Chirurgie Pédiatrique [CHRU Montpellier] Institut Desbrest d'Epidémiologie et de Santé Publique CHU Trousseau [Tours] CH Colmar Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique] Centre Hospitalier Le Mans (CH Le Mans) Centre Hospitalier Regional d'Orléans Centre Hospitalier Universitaire de Toulouse Hôpital universitaire Robert Debré [Reims] Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Hôpital Necker - Enfants Malades [AP-HP] Imagine - Institut des maladies génétiques (IHU) Hôpital Necker - Enfants Malades [AP-HP] Centre Hospitalier Universitaire d'Angers Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques
• Publié dans Journal of Pediatric Gastroenterology and Nutrition le 25/10/2020

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Résumé : Objectives: The present study aimed to assess long-term functional outcomes of children with anorectal malformations (ARMs) across a network of expert centers in France. Methods: Retrospective cross-sectional study of patients ages 6-30 years that had been surgically treated for ARM. Patient and ARM characteristics (eg, level, surgical approach) and functional outcomes were assessed in the different age groups. Results: Among 367 patients, there were 155 females (42.2%) and 212 males (57.8%), 188 (51.2%) cases with, and 179 (48.8%) higher forms without, perineal fistula. Univariate and multivariate statistical analyses with logistic regression showed correlation between the level of the rectal blind pouch and voluntary bowel movements (odds ratio [OR] = 1.84 [1.31-2.57], P < 0.001), or soiling (OR = 1.72 [1.31-2.25], P < 0.001), which was also associated with the inability to discriminate between stool and gas (OR = 2.45 [1.28-4.67], P = 0.007) and the presence of constipation (OR = 2.97 [1.74-5.08], P < 0.001). Risk factors for constipation were sacral abnormalities [OR = 2.26 [1.23-4.25], P = 0.01) and surgical procedures without an abdominal approach (OR = 2.98 [1.29-6.87], P = 0.01). Only the holding of voluntary bowel movements and soiling rates improved with age. Conclusion: This cross-sectional study confirms a strong association between anatomical status and functional outcomes in patients surgically treated for ARM. It specifically highlights the need for long-term follow-up of all patients to help them with supportive care.

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Fichiers liés : PMID 35849503.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2022
• Auteurs : Krystel AouadPhilippe GaudinOlivier VittecoqJacques MorelJean-Marie BerthelotEric SenbelThierry SchaeverbekeFrédéric LiotéRené-Marc FlipoAlexandrine PintaF. GuilleminBruno Fautrel
• Organismes : CHU Pitié-Salpêtrière [AP-HP] Service de Rhumatologie [CHU Rouen] Université de Rouen Normandie Centre Hospitalier Régional Universitaire [Montpellier] Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Service de Rhumatologie [CHU Sainte Marguerite] Centre Hospitalier Universitaire de Bordeaux Assistance publique - Hôpitaux de Paris (AP-HP) Laboratoire Roche [Boulogne-Billancourt] Centre d'investigation clinique [Nancy] CHU Pitié-Salpêtrière [AP-HP] Institut Pierre Louis d'Epidémiologie et de Santé Publique
• Publié dans Rheumatology le 29/10/2020

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Résumé : Objective The Flare Assessment in RA (FLARE-RA) self-administered questionnaire aims to identify patients who had flare in the interval between two consultations. This study aimed to establish a threshold for FLARE-RA score to identify RA flare. Methods The Tocilizumab SubCutAneous study evaluated the efficacy and safety of s.c. tocilizumab (TCZ) to patients with active RA. Disease activity was assessed with the DAS28ESR at baseline and at week 2 (W2), W4, W12 and W24. The FLARE-RA questionnaire was administered at W12 and W24. Patient satisfaction, assessed at baseline and W24 with the Patient Acceptable Symptom State (PASS), was used as a surrogate marker of no flare. A correlation was sought between the FLARE-RA score at W12 and W24 and the area under the receiver operating characteristic (ROC) curve (AUC) for monthly DAS28ESR. The optimal FLARE-RA cut-off below which patient satisfaction reached the PASS was explored with an ROC curve. Results A total of 139 patients were included (mean age 57.3 ± 13.8 years, 74.1% women, mean RA duration 10.8 ± 9.2 years, mean DAS28ESR 5.8 ± 1.1). The correlation between the FLARE-RA score and DAS28ESR AUC was moderate at all times: ρ = 0.41 at W12 (P < 0.0001) and 0.51 at W24 (P < 0.0001). The optimal cut-off for the FLARE-RA score to identify absence of flare (i.e. an acceptable situation based on the PASS) was 2.3 with an AUC of 0.81. Conclusion FLARE-RA and DAS28ESR assessment differ; we propose a FLARE-RA cut-off of 2.3, below which the situation (i.e. without flare) is acceptable for patients.

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Fichiers liés : 2021 Aouad et al., Cut.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2022
• Auteurs : Emmanuel EstèveDavid BuobFrédéric JammeChantal JouanneauSlavka KascakovaJean-Philippe HaymannEmmanuel LetavernierLouise GalmichePierre RoncoMichel DaudonDominique BazinMatthieu Réfrégiers
• Organismes : CoRaKiD - Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée CHU Tenon [AP-HP] CoRaKiD - Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée CHU Tenon [AP-HP] Synchrotron SOLEIL CoRaKiD - Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée Synchrotron SOLEIL Departement Hospitalo-Universitaire Hepatinov [Hôpital Paul Brousse - APHP] CoRaKiD - Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée CHU Tenon [AP-HP] CoRaKiD - Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée CHU Tenon [AP-HP] Service d'anatomie pathologique [CHU Necker] CoRaKiD - Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée CoRaKiD - Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée CHU Tenon [AP-HP] Institut de Chimie Physique Laboratoire de Physique des Solides Centre de biophysique moléculaire Synchrotron SOLEIL
• Publié dans Journal of Synchrotron Radiation le 26/10/2020

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Résumé : Renal oxalosis is a rare cause of renal failure whose diagnosis can be challenging. Synchrotron deep ultraviolet (UV) fluorescence was assayed to improve oxalosis detection on kidney biopsies spatial resolution and sensitivity compared with the Fourier transform infrared microspectroscopy gold standard. The fluorescence spectrum of synthetic mono-, di-and tri-hydrated calcium oxalate was investigated using a microspectrometer coupled to the synchrotron UV beamline DISCO, Synchrotron SOLEIL, France. The obtained spectra were used to detect oxalocalcic crystals in a case control study of 42 human kidney biopsies including 19 renal oxalosis due to primary (PHO, n = 11) and secondary hyperoxaluria (SHO, n = 8), seven samples from PHO patients who received combined kidney and liver transplants, and 16 controls. For all oxalocalcic hydrates samples, a fluorescence signal is detected at 420 nm. These spectra were used to identify standard oxalocalcic crystals in patients with PHO or SHO. They also revealed micrometric crystallites as well as non-aggregated oxalate accumulation in tubular cells. A nine-points histological score was established for the diagnosis of renal oxalosis with 100% specificity (76-100) and a 73% sensitivity (43-90). Oxalate tubular accumulation and higher histological score were correlated to lower estimated glomerular filtration rate and higher urinary oxalate over creatinine ratio.

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Fichiers liés : yn5078.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2022
• Auteurs : Enrica CavedoPhilippe TranUrielle ThoprakarnJean-Baptiste MartiniAntoine MovschinChristine DelmaireFlorent GarielDamien HeidelbergNadya PyatigorskayaSébastian StröerPierre Krolak-SalmonFrançois CottonClarisse Longo dos SantosDidier Dormont
• Organismes : Qynapse Algorithms, models and methods for images and signals of the human brain = Algorithmes, modèles et méthodes pour les images et les signaux du cerveau humain [ICM Paris] Qynapse Qynapse Qynapse Qynapse Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP] Hôpital Pellegrin Centre Hospitalier Lyon Sud [CHU - HCL] CHU Pitié-Salpêtrière [AP-HP] Institut du Cerveau = Paris Brain Institute CHU Pitié-Salpêtrière [AP-HP] Institut du Cerveau = Paris Brain Institute Centre Hospitalier Lyon Sud [CHU - HCL] Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center Centre Hospitalier Lyon Sud [CHU - HCL] Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé Qynapse Algorithms, models and methods for images and signals of the human brain = Algorithmes, modèles et méthodes pour les images et les signaux du cerveau humain [ICM Paris] Institut du Cerveau = Paris Brain Institute CHU Pitié-Salpêtrière [AP-HP]
• Publié dans European Radiology le 23/10/2020

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Résumé : Objectives QyScore® is an imaging analysis tool certified in Europe (CE marked) and the US (FDA cleared) for the automatic volumetry of grey and white matter (GM and WM respectively), hippocampus (HP), amygdala (AM), and white matter hyperintensity (WMH). Here we compare QyScore® performances with the consensus of expert neuroradiologists. Methods Dice similarity coefficient (DSC) and the relative volume difference (RVD) for GM, WM volumes were calculated on 50 3DT1 images. DSC and the F1 metrics were calculated for WMH on 130 3DT1 and FLAIR images. For each index, we identified thresholds of reliability based on current literature review results. We hypothesized that DSC/F1 scores obtained using QyScore® markers would be higher than the threshold. In contrast, RVD scores would be lower. Regression analysis and Bland–Altman plots were obtained to evaluate QyScore® performance in comparison to the consensus of three expert neuroradiologists. Results The lower bound of the DSC/F1 confidence intervals was higher than the threshold for the GM, WM, HP, AM, and WMH, and the higher bounds of the RVD confidence interval were below the threshold for the WM, GM, HP, and AM. QyScore®, compared with the consensus of three expert neuroradiologists, provides reliable performance for the automatic segmentation of the GM and WM volumes, and HP and AM volumes, as well as WMH volumes. Conclusions QyScore® represents a reliable medical device in comparison with the consensus of expert neuroradiologists. Therefore, QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases. Key Points • QyScore® provides reliable automatic segmentation of brain structures in comparison with the consensus of three expert neuroradiologists. • QyScore® automatic segmentation could be performed on MRI images using different vendors and protocols of acquisition. In addition, the fast segmentation process saves time over manual and semi-automatic methods. • QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases.

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Fichiers liés : Cavedo2022_Article_ValidationOfAnAutomaticToolFor.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2022
• Auteurs : Arnaud DelvalB. GirardL. LacanL. ChatonF. FlameinLaurent StormePhilippe DerambureSylvie Nguyen The TichM. D. LamblinNacim Betrouni
• Organismes : Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 Evaluation des technologies de santé et des pratiques médicales - ULR 2694 Lille Neurosciences & Cognition - U 1172 Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837
• Publié dans European Journal of Paediatric Neurology le 30/10/2020

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Résumé : ObjectivesOur objective was to evaluate the potential additional value of electroencephalogram (EEG) and evoked potentials in neonates with hypoxic-ischemic encephalopathy to predict their disability at 1 and 2 years old.Methods30 full-term infants after perinatal asphyxia who underwent therapeutic hypothermia were evaluated at 1 year and 2 years for disability using International Classification of Functioning, Disability and Health classification. Scores for EEG, sensory evoked potentials and brainstem auditory evoked potentials were evaluated after withdrawal of therapeutic hypothermia that lasted 72 h. A regression approach was investigated to build models allowing to distinguish neonates according to their disability at 1 and 2 years. Two models were built, the first by considering the clinical data and EEG before and after therapeutic hypothermia and the second by incorporating evoked potentials recording.ResultsAdding EEG and evoked potentials data after rewarming improved dramatically the accuracy of the model considering outcome at 1 and 2 years.InterpretationWe propose to record systematically EEG and evoked potentials following rewarming to predict the outcome of neonates with hypoxic ischemic encephalopathy. Combination of altered evoked potentials with no improvement of EEG after rewarming appeared to be a robust criterion for a poor outcome.

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Fichiers liés : S1090379821002038.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2022
• Auteurs : Damien LogeartEmmannuelle BerthelotNicolas BihryRomain EschalierMuriel SalvatPhilippe GarconJean-Christophe EicherAriel CohenJean-Michel TartiereAlireza SamadiErwan DonalPascal DegrooteNathan MewtonNicolas MansencalPierre RaphaelNachwan GhanemMarie-France SérondeChristophe ChavelasYann RosamelFlorence BeauvaisJean-Philippe KevorkianAbdourahmane DialloÉric VicautRichard Isnard
• Organismes : Hôpital Lariboisière-Fernand-Widal [APHP] Centre d'Investigation Clinique [CHU Clermont-Ferrand] Hôpital Michallon Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Laboratoire Traitement du Signal et de l'Image Hôpital Louis Pradel [CHU - HCL] Hôpital Ambroise Paré [AP-HP] Hôpital Lariboisière-Fernand-Widal [APHP] Hôpital Lariboisière-Fernand-Widal [APHP] Hôpital Lariboisière-Fernand-Widal [APHP] CHU Pitié-Salpêtrière [AP-HP]
• Publié dans European Journal of Heart Failure le 22/10/2020

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Résumé : Aims Hospitalization for acute heart failure (HF) is followed by a vulnerable time with increased risk of readmission or death, thus requiring particular attention after discharge. In this study, we examined the impact of intensive, early follow-up among patients at high readmission risk at discharge after treatment for acute HF. Methods and results Hospitalized acute HF patients were included with at least one of the following: previous acute HF < 6 months, systolic blood pressure <= 110 mmHg, creatininaemia >= 180 mu mol/L, or B-type natriuretic peptide >= 350 pg/mL or N-terminal pro B-type natriuretic peptide >= 2200 pg/mL. Patients were randomized to either optimized care and education with serial consultations with HF specialist and dietician during the first 2-3 weeks, or to standard post-discharge care according to guidelines. The primary endpoint was all-cause death or first unplanned hospitalization during 6-month follow-up. Among 482 randomized patients (median age 77 and median left ventricular ejection fraction 35%), 224 were hospitalized or died. In the intensive group, loop diuretics (46%), beta-blockers (49%), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (39%) and mineralocorticoid receptor antagonists (47%) were titrated. No difference was observed between groups for the primary endpoint (hazard ratio 0.97; 95% confidence interval 0.74-1.26), nor for mortality at 6 or 12 months or unplanned HF rehospitalization. Additionally, no difference between groups according to age, previous HF and left ventricular ejection fraction was found. Conclusions In high-risk HF, intensive follow-up early post-discharge did not improve outcomes. This vulnerable post-discharge time requires further studies to clarify useful transitional care services.

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Fichiers liés : Logeart et al-2021-Early and short-term intensive management after discharge for patients.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2022
• Auteurs : Salim Si-MohamedJoel GreffierJade MiailhesSara BoccaliniPierre-Antoine RodeschAurélie VuillodNiels van der WerfDjamel DabliDamien RacineDavid RotzingerFabio BecceYoad YagilPhilippe CoulonAlain VlassenbroekL. BousselJean-Paul BeregiPhilippe Douek
• Organismes : Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé Modeling & analysis for medical imaging and Diagnosis Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé Modeling & analysis for medical imaging and Diagnosis
• Publié dans European Radiology le 23/10/2020

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2022
• Auteurs : Anne TrinhRaeeka KhamariQuentin FovezFrançois-Xavier MahonBéatrice TurcqDidier BouscaryPatrice MaboudouMarie JoncquelValérie CoiteuxNicolas GermainWilliam LaineSalim DekioukSandrine Jean-PierreVeronique Maguer-SattaBart GhesquiereThierry IdziorekBruno QuesnelJérôme KluzaPhilippe Marchetti
• Organismes : Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 Centre Hospitalier Régional Universitaire [CHU Lille] Institut pour la recherche sur le cancer de Lille [Lille] Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 Centre Hospitalier Régional Universitaire [CHU Lille] Institut pour la recherche sur le cancer de Lille [Lille] Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 Centre Hospitalier Régional Universitaire [CHU Lille] Institut pour la recherche sur le cancer de Lille [Lille] Actions for OnCogenesis understanding and Target Identification in ONcology Institut Bergonié [Bordeaux] Actions for OnCogenesis understanding and Target Identification in ONcology Institut Bergonié [Bordeaux] Centre National de la Recherche Scientifique Université de Bordeaux Institut Cochin Hôpital Cochin [AP-HP] Centre Hospitalier Régional Universitaire [CHU Lille] Centre Hospitalier Régional Universitaire [CHU Lille] Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 Centre Hospitalier Régional Universitaire [CHU Lille] Institut pour la recherche sur le cancer de Lille [Lille] Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 Centre Hospitalier Régional Universitaire [CHU Lille] Institut pour la recherche sur le cancer de Lille [Lille] Université de Lille Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 Centre Hospitalier Régional Universitaire [CHU Lille] Institut pour la recherche sur le cancer de Lille [Lille] Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 Centre Hospitalier Régional Universitaire [CHU Lille] Institut pour la recherche sur le cancer de Lille [Lille] Centre de Recherche en Cancérologie de Lyon Centre de Recherche en Cancérologie de Lyon Catholic University of Leuven = Katholieke Universiteit Leuven Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 Centre Hospitalier Régional Universitaire [CHU Lille] Institut pour la recherche sur le cancer de Lille [Lille] Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 Centre Hospitalier Régional Universitaire [CHU Lille] Institut pour la recherche sur le cancer de Lille [Lille] Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 Centre Hospitalier Régional Universitaire [CHU Lille] Institut pour la recherche sur le cancer de Lille [Lille] Institut National de la Santé et de la Recherche Médicale Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 Centre Hospitalier Régional Universitaire [CHU Lille] Institut pour la recherche sur le cancer de Lille [Lille]
• Publié dans Molecular metabolism le 26/10/2020

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Résumé : Long-term treatment with tyrosine kinase inhibitors (TKI) represents an effective treatment for chronic myeloid leukemia (CML) and discontinuation of TKI therapy is now proposed to patient with deep molecular responses. However, evidence demonstrating that TKI are unable to fully eradicate dormant leukemic stem cells indicate that new therapeutic strategies are needed to prevent molecular relapses. We investigated the metabolic pathways responsible for CML surviving to Imatinib exposure and its potential therapeutic utility to improve the efficiency of TKI against CML stem cells. Using complementary cell-based techniques, we demonstrated that TKI suppressed glycolysis in a large panel of BCR-ABL1 + cell lines as well as in primary CD34+ stem-like cells from CML patients. However, compensatory glutamine-dependent mitochondrial oxidation supported ATP synthesis and CML cell survival. Glutamine metabolism was inhibited by L-asparaginases such as Kidrolase without inducing predominant CML cell death. Clinically relevant concentrations of TKI render CML progenitors and stem cells susceptible to Kidrolase. The combination of TKI with L-asparaginase reactivated the intinsic apoptotic pathway leading to efficient CML cell death. Thus, targeting glutamine metabolism with the clinically-approved drug Kidrolase, in combination with TKI that suppress glycolysis represents an effective and widely applicable therapeutic strategy for eradicating CML stem cells.

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Fichiers liés : 1-s2.0-S2212877821002684-main.pdf

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