66 research outputs found
BCR-associated factors driving chronic lymphocytic leukemia cells proliferation ex vivo
International audienceA chronic antigenic stimulation is believed to sustain the leukemogenic development of chronic lymphocytic leukemia (CLL) and most of lymphoproliferative malignancies developed from mature B cells. Reproducing a proliferative stimulation ex vivo is critical to decipher the mechanisms of leukemogenesis in these malignancies. However, functional studies of CLL cells remains limited since current ex vivo B cell receptor (BCR) stimulation protocols are not sufficient to induce the proliferation of these cells, pointing out the need of mandatory BCR co-factors in this process. Here, we investigated benefits of several BCR co-stimulatory molecules (IL-2, IL-4, IL-15, IL-21 and CD40 ligand) in multiple culture conditions. Our results demonstrated that BCR engagement (anti-IgM ligation) concomitant to CD40 ligand, IL-4 and IL-21 stimulation allowed CLL cells proliferation ex vivo. In addition, we established a proliferative advantage for ZAP70 positive CLL cells, associated to an increased phosphorylation of ZAP70/SYK and STAT6. Moreover, the use of a tri-dimensional matrix of methylcellulose and the addition of TLR9 agonists further increased this proliferative response. This ex vivo model of BCR stimulation with T-derived cytokines is a relevant and efficient model for functional studies of CLL as well as lymphoproliferative malignancies. Like in most mature lymphoproliferative malignancies, an antigenic stimulation is believed to drive the leukemo-genic process in chronic lymphocytic leukemia (CLL) 1-3. A restricted use of IGHV genes and the existence of ste-reotypic B cell receptor (BCR) on CLL cells 4-6 provides evidence in favor of antigenic stimulation where different microbial antigens, as well as auto-antigens, have been suspected as actors of this chronic stimulation 7. In addition , a chronic BCR self-activation has been shown in subtypes of CLL cells 8. Moreover, several signaling aberrations have been described downstream of the BCR, notably in aggressive CLL with unmutated IGHV (UM-CLL), in which the expression of ZAP70 reinforces BCR responsiveness 9-12. BCR activation, which is essential for the physiological development of lymphocytes 13 would also be indispensable for the survival and proliferation of CLL cells in vivo 2. Accordingly, withdrawal of this stimulation is believed to be responsible for the rapid spontaneous apoptosis of CLL cells ex vivo 14. The cellular consequences of this BCR activation has been extensively studied an
Deep-Learning Assessed Muscular Hypodensity Independently Predicts Mortality in DLBCL Patients Younger Than 60 Years.
[en] BACKGROUND: Muscle depletion (MD) assessed by computed tomography (CT) has been shown to be a predictive marker in solid tumors, but has not been assessed in non-Hodgkin's lymphomas. Despite software improvements, MD measurement remains highly time-consuming and cannot be used in clinical practice.
METHODS: This study reports the development of a Deep-Learning automatic segmentation algorithm (DLASA) to measure MD, and investigate its predictive value in a cohort of 656 diffuse large B cell lymphoma (DLBCL) patients included in the GAINED phase III prospective trial (NCT01659099).
RESULTS: After training on a series of 190 patients, the DLASA achieved a Dice coefficient of 0.97 ± 0.03. In the cohort, the median skeletal muscle index was 50.2 cm2/m2 and median muscle attenuation (MA) was 36.1 Hounsfield units (HU). No impact of sarcopenia was found on either progression free survival (PFS) or overall survival (OS). Muscular hypodensity, defined as MA below the tenth percentile according to sex, was associated with a lower OS and PFS, respectively (HR = 2.80 (95% CI 1.58-4.95), p < 0.001, and HR = 2.22 (95% CI 1.43-3.45), p < 0.001). Muscular hypodensity appears to be an independent risk factor for mortality in DLBCL and because of DLASA can be estimated in routine practice
SARS-CoV-2 Infection in Patients With Waldenström's Macroglobulinemia: A Multicenter International Cohort Study
The coronavirus disease 2019 (COVID-19) pandemic has represented a huge challenge for vulnerable patients affected with hematological malignancies.1,2 So far, heterogeneous series on patients with lymphoma and COVID-19 have been published with mortality rates ranging from 25% to 40%,3â8 with only limited information about specific neoplasms.Peer reviewe
A French multicentric prospective prognostic cohort with epidemiological, clinical, biological and treatment information to improve knowledge on lymphoma patients: study protocol of the "REal world dAta in LYmphoma and survival in adults" (REALYSA) cohort.
BACKGROUND: Age-adjusted lymphoma incidence rates continue to rise in France since the early 80's, although rates have slowed since 2010 and vary across subtypes. Recent improvements in patient survival in major lymphoma subtypes at population level raise new questions about patient outcomes (i.e. quality of life, long-term sequelae). Epidemiological studies have investigated factors related to lymphoma risk, but few have addressed the extent to which socioeconomic status, social institutional context (i.e. healthcare system), social relationships, environmental context (exposures), individual behaviours (lifestyle) or genetic determinants influence lymphoma outcomes, especially in the general population. Moreover, the knowledge of the disease behaviour mainly obtained from clinical trials data is partly biased because of patient selection. METHODS: The REALYSA ("REal world dAta in LYmphoma and Survival in Adults") study is a real-life multicentric cohort set up in French areas covered by population-based cancer registries to study the prognostic value of epidemiological, clinical and biological factors with a prospective 9-year follow-up. We aim to include 6000 patients over 4 to 5âyears. Adult patients without lymphoma history and newly diagnosed with one of the following 7 lymphoma subtypes (diffuse large B-cell, follicular, marginal zone, mantle cell, Burkitt, Hodgkin, mature T-cell) are invited to participate during a medical consultation with their hematologist. Exclusion criteria are: having already received anti-lymphoma treatment (except pre-phase) and having a documented HIV infection. Patients are treated according to the standard practice in their center. Clinical data, including treatment received, are extracted from patients' medical records. Patients' risk factors exposures and other epidemiological data are obtained at baseline by filling out a questionnaire during an interview led by a clinical research assistant. Biological samples are collected at baseline and during treatment. A virtual tumor biobank is constituted for baseline tumor samples. Follow-up data, both clinical and epidemiological, are collected every 6âmonths in the first 3âyears and every year thereafter. DISCUSSION: This cohort constitutes an innovative platform for clinical, biological, epidemiological and socio-economic research projects and provides an opportunity to improve knowledge on factors associated to outcome of lymphoma patients in real life. TRIAL REGISTRATION: 2018-A01332-53, ClinicalTrials.gov identifier: NCT03869619
Methodological developments in proteomic analysis for the discovery and validation of biomarkers in B-cells lymphoid malignancies in adults
Le dĂ©veloppement actuel trĂšs rapide des diffĂ©rentes approches « omiques » gĂ©nĂšre un grand nombre de biomarqueurs potentiels, en particulier dans le domaine de la cancĂ©rologie.Lâanalyse protĂ©omique par spectromĂ©trie de masse a particuliĂšrement bĂ©nĂ©ficiĂ© des progrĂšs technologiques rĂ©cents qui ont permis la mise au point de nouvelles approches quantitatives globales ou ciblĂ©es. NĂ©anmoins, peu de biomarqueurs potentiels finissent par ĂȘtre concrĂštement utilisĂ©s en pratique clinique, nĂ©cessitant lâoptimisation des diffĂ©rentes Ă©tapes de leur dĂ©veloppement.Dans la continuitĂ© des travaux ayant abouti Ă lâidentification de biomarqueurs diagnostiques dans les hĂ©mopathies lymphoĂŻdes B, ce travail de thĂšse a permis le dĂ©veloppement dâune mĂ©thode dâanalyse protĂ©omique ciblĂ©e pour la vĂ©rification et la validation de nouveaux biomarqueurs potentiels. La possibilitĂ© dâappliquer des stratĂ©gies quantitatives globales Ă un trĂšs grand nombre dâĂ©chantillons a pu ĂȘtre dĂ©montrĂ©e. Lâapplication de ces stratĂ©gies quantitatives globales Ă du tissu ganglionnaire provenant de lymphomes agressifs a permis dâidentifier des biomarqueurs potentiellement associĂ©s Ă une rĂ©sistance au traitement. Enfin,le mode de prĂ©paration tube-gel, facilitant lâĂ©tude dâun grand nombre dâĂ©chantillons, a Ă©tĂ© validĂ© pour la rĂ©alisation dâanalyses protĂ©omiques diffĂ©rentielles.The current development of new « omics » technologies has led to the discovery of a large number of potential biomarkers, particularly in the field of oncology. Proteomics analysis bymass spectrometry have particularly benefited from these technological advances with the development of new global or targeted quantitative approaches. Nevertheless, only a few numbers of potential biomarkers are finally used in clinical practice, requiring further optimization of the development process. Following the initial identification of biomarkers in the diagnosis of lymphoid malignancies performed previously, this thesis has allowed the development of a targeted proteomics method that can be used for the validation of new potential biomarkers. The ability of analysing a large number of samples with a global quantitative approach has also been demonstrated. The application of these global quantitative strategies on lymph node tissue of aggressive lymphoma has permitted the identification of potential new biomarkers associated with chemorefractoriness. Lastly, a tube-gel protocol facilitating the analysis of a large number of samples has been validated for differential proteomics studies
Développements méthodologiques en analyse protéomique pour la découverte et la validation de biomarqueurs dans les hémopathies lymphoïdes B de l'adulte
The current development of new « omics » technologies has led to the discovery of a large number of potential biomarkers, particularly in the field of oncology. Proteomics analysis bymass spectrometry have particularly benefited from these technological advances with the development of new global or targeted quantitative approaches. Nevertheless, only a few numbers of potential biomarkers are finally used in clinical practice, requiring further optimization of the development process. Following the initial identification of biomarkers in the diagnosis of lymphoid malignancies performed previously, this thesis has allowed the development of a targeted proteomics method that can be used for the validation of new potential biomarkers. The ability of analysing a large number of samples with a global quantitative approach has also been demonstrated. The application of these global quantitative strategies on lymph node tissue of aggressive lymphoma has permitted the identification of potential new biomarkers associated with chemorefractoriness. Lastly, a tube-gel protocol facilitating the analysis of a large number of samples has been validated for differential proteomics studies.Le dĂ©veloppement actuel trĂšs rapide des diffĂ©rentes approches « omiques » gĂ©nĂšre un grand nombre de biomarqueurs potentiels, en particulier dans le domaine de la cancĂ©rologie.Lâanalyse protĂ©omique par spectromĂ©trie de masse a particuliĂšrement bĂ©nĂ©ficiĂ© des progrĂšs technologiques rĂ©cents qui ont permis la mise au point de nouvelles approches quantitatives globales ou ciblĂ©es. NĂ©anmoins, peu de biomarqueurs potentiels finissent par ĂȘtre concrĂštement utilisĂ©s en pratique clinique, nĂ©cessitant lâoptimisation des diffĂ©rentes Ă©tapes de leur dĂ©veloppement.Dans la continuitĂ© des travaux ayant abouti Ă lâidentification de biomarqueurs diagnostiques dans les hĂ©mopathies lymphoĂŻdes B, ce travail de thĂšse a permis le dĂ©veloppement dâune mĂ©thode dâanalyse protĂ©omique ciblĂ©e pour la vĂ©rification et la validation de nouveaux biomarqueurs potentiels. La possibilitĂ© dâappliquer des stratĂ©gies quantitatives globales Ă un trĂšs grand nombre dâĂ©chantillons a pu ĂȘtre dĂ©montrĂ©e. Lâapplication de ces stratĂ©gies quantitatives globales Ă du tissu ganglionnaire provenant de lymphomes agressifs a permis dâidentifier des biomarqueurs potentiellement associĂ©s Ă une rĂ©sistance au traitement. Enfin,le mode de prĂ©paration tube-gel, facilitant lâĂ©tude dâun grand nombre dâĂ©chantillons, a Ă©tĂ© validĂ© pour la rĂ©alisation dâanalyses protĂ©omiques diffĂ©rentielles
Methodological developments in proteomic analysis for the discovery and validation of biomarkers in B-cells lymphoid malignancies in adults
Le dĂ©veloppement actuel trĂšs rapide des diffĂ©rentes approches « omiques » gĂ©nĂšre un grand nombre de biomarqueurs potentiels, en particulier dans le domaine de la cancĂ©rologie.Lâanalyse protĂ©omique par spectromĂ©trie de masse a particuliĂšrement bĂ©nĂ©ficiĂ© des progrĂšs technologiques rĂ©cents qui ont permis la mise au point de nouvelles approches quantitatives globales ou ciblĂ©es. NĂ©anmoins, peu de biomarqueurs potentiels finissent par ĂȘtre concrĂštement utilisĂ©s en pratique clinique, nĂ©cessitant lâoptimisation des diffĂ©rentes Ă©tapes de leur dĂ©veloppement.Dans la continuitĂ© des travaux ayant abouti Ă lâidentification de biomarqueurs diagnostiques dans les hĂ©mopathies lymphoĂŻdes B, ce travail de thĂšse a permis le dĂ©veloppement dâune mĂ©thode dâanalyse protĂ©omique ciblĂ©e pour la vĂ©rification et la validation de nouveaux biomarqueurs potentiels. La possibilitĂ© dâappliquer des stratĂ©gies quantitatives globales Ă un trĂšs grand nombre dâĂ©chantillons a pu ĂȘtre dĂ©montrĂ©e. Lâapplication de ces stratĂ©gies quantitatives globales Ă du tissu ganglionnaire provenant de lymphomes agressifs a permis dâidentifier des biomarqueurs potentiellement associĂ©s Ă une rĂ©sistance au traitement. Enfin,le mode de prĂ©paration tube-gel, facilitant lâĂ©tude dâun grand nombre dâĂ©chantillons, a Ă©tĂ© validĂ© pour la rĂ©alisation dâanalyses protĂ©omiques diffĂ©rentielles.The current development of new « omics » technologies has led to the discovery of a large number of potential biomarkers, particularly in the field of oncology. Proteomics analysis bymass spectrometry have particularly benefited from these technological advances with the development of new global or targeted quantitative approaches. Nevertheless, only a few numbers of potential biomarkers are finally used in clinical practice, requiring further optimization of the development process. Following the initial identification of biomarkers in the diagnosis of lymphoid malignancies performed previously, this thesis has allowed the development of a targeted proteomics method that can be used for the validation of new potential biomarkers. The ability of analysing a large number of samples with a global quantitative approach has also been demonstrated. The application of these global quantitative strategies on lymph node tissue of aggressive lymphoma has permitted the identification of potential new biomarkers associated with chemorefractoriness. Lastly, a tube-gel protocol facilitating the analysis of a large number of samples has been validated for differential proteomics studies
Valeur de l'allogreffe de cellules souches hématopoïétiques à conditionnement atténué en traitement de consolidation de la premiÚre rémission complÚte d'une leucémie aiguë myéloblastique (analyse des resultats du protocole LAM 2001 chez les patients ùgés de 51 à 60 ans avec un donneur familial HLA identique.)
STRASBOURG-Medecine (674822101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Efficacy of Serotherapy on an N501Y Variant of SARS-CoV-2 in a Patient With Chronic Lymphocytic Leukemia
Highâdose therapy with autologous stem cells transplantation in BingâNeel syndrome: A retrospective analysis of 14 cases
International audienc
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