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Article ; Online: An agent-based model of monocyte differentiation into tumour-associated macrophages in chronic lymphocytic leukemia

Nina Verstraete / Malvina Marku / Marcin Domagala / Hélène Arduin / Julie Bordenave / Jean-Jacques Fournié / Loïc Ysebaert / Mary Poupot / Vera Pancaldi

iScience, Vol 26, Iss 6, Pp 106897- (2023)

2023

Abstract: Summary: Monocyte-derived macrophages help maintain tissue homeostasis and defend the organism against pathogens. In tumors, recent studies have uncovered complex macrophage populations, including tumor-associated macrophages, which support tumorigenesis ...

Abstract	Summary: Monocyte-derived macrophages help maintain tissue homeostasis and defend the organism against pathogens. In tumors, recent studies have uncovered complex macrophage populations, including tumor-associated macrophages, which support tumorigenesis through cancer hallmarks such as immunosuppression, angiogenesis, or matrix remodeling. In the case of chronic lymphocytic leukemia, these macrophages are known as nurse-like cells (NLCs) and they protect leukemic cells from spontaneous apoptosis, contributing to their chemoresistance. We propose an agent-based model of monocyte differentiation into NLCs upon contact with leukemic B cells in vitro. We performed patient-specific model optimization using cultures of peripheral blood mononuclear cells from patients. Using our model, we were able to reproduce the temporal survival dynamics of cancer cells in a patient-specific manner and to identify patient groups related to distinct macrophage phenotypes. Our results show a potentially important role of phagocytosis in the polarization process of NLCs and in promoting cancer cells’ enhanced survival.
Keywords	Health sciences ; Immunology ; Computational bioinformatics ; Cancer ; Science ; Q
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Venetoclax with high‐dose methotrexate and rituximab seem effective and well‐tolerated in the treatment of central nervous system involvement of chronic lymphocytic leukemia

Guillaume Beziat / Martin Gauthier / Caroline Protin / Lucie Oberic / Fleur Lerebours / Jasmine Carlier / Loïc Ysebaert

Clinical Case Reports, Vol 8, Iss 2, Pp 269-

A case report

2020 Volume 273

Abstract: Abstract Venetoclax with high‐dose methotrexate and rituximab seem effective and safe to treat central nervous system involvement of chronic lymphocytic leukemia. ...

Abstract	Abstract Venetoclax with high‐dose methotrexate and rituximab seem effective and safe to treat central nervous system involvement of chronic lymphocytic leukemia.
Keywords	central nervous system involvement ; chronic lymphocytic leukemia ; venetoclax ; Medicine ; R ; Medicine (General) ; R5-920
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Limited Sampling Strategy for Determination of Ibrutinib Plasma Exposure

Félicien Le Louedec / Fanny Gallais / Fabienne Thomas / Mélanie White-Koning / Ben Allal / Caroline Protin / Loïc Ysebaert / Étienne Chatelut / Florent Puisset

Pharmaceuticals, Vol 14, Iss 2, p

Joint Analyses with Metabolite Data

2021 Volume 162

Abstract: Therapeutic drug monitoring of ibrutinib is based on the area under the curve of concentration vs. time (AUC IBRU ) instead of trough concentration (C min,ss ) because of a limited accumulation in plasma. Our objective was to identify a limited sampling ... ...

Abstract	Therapeutic drug monitoring of ibrutinib is based on the area under the curve of concentration vs. time (AUC IBRU ) instead of trough concentration (C min,ss ) because of a limited accumulation in plasma. Our objective was to identify a limited sampling strategy (LSS) to estimate AUC IBRU associated with Bayesian estimation. The actual AUC IBRU of 85 patients was determined by the Bayesian analysis of the full pharmacokinetic profile of ibrutinib concentrations (pre-dose T0 and 0.5, 1, 2, 4 and 6 h post-dose) and experimental AUC IBRU were derived considering combinations of one to four sampling times. The T0–1–2–4 design was the most accurate LSS (root-mean-square error RMSE = 11.0%), and three-point strategies removing the 1 h or 2 h points (RMSE = 22.7% and 14.5%, respectively) also showed good accuracy. The correlation between the actual AUC IBRU and C min,ss was poor ( r 2 = 0.25). The joint analysis of dihydrodiol-ibrutinib metabolite concentrations did not improve the predictive performance of AUC IBRU . These results were confirmed in a prospective validation cohort ( n = 27 patients). At least three samples, within the pre-dose and 4 h post-dose period, are necessary to estimate ibrutinib exposure accurately.
Keywords	ibrutinib ; metabolite ; therapeutic drug monitoring ; Bayesian analysis ; pharmacokinetics ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Subject code	333
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Spectrum of Kidney Disorders Associated with T-Cell Immunoclones

Alexis Piedrafita / François Vergez / Julie Belliere / Nais Prades / Magali Colombat / Antoine Huart / Jean-Baptiste Rieu / Stéphanie Lagarde / Arnaud Del Bello / Nassim Kamar / Dominique Chauveau / Camille Laurent / Lucie Oberic / Loïc Ysebaert / David Ribes / Stanislas Faguer

Journal of Clinical Medicine, Vol 11, Iss 604, p

2022 Volume 604

Abstract: Large granular T-cell leukemia is a clonal hematological condition often associated with autoimmune disorders. Whether small-sized T-cell clones that are otherwise asymptomatic can promote immune kidney disorders remains elusive. In this monocentric ... ...

Abstract	Large granular T-cell leukemia is a clonal hematological condition often associated with autoimmune disorders. Whether small-sized T-cell clones that are otherwise asymptomatic can promote immune kidney disorders remains elusive. In this monocentric retrospective cohort in a tertiary referral center in France, we reviewed characteristics of 29 patients with T-cell clone proliferation and autoimmune kidney disorders. Next-generation sequencing of the T-cell receptor of circulating T-cells was performed in a subset of patients. The T-cell clones were detected owing to systematic screening (mean count 0.32 × 10 9 /L, range 0.13–3.7). Strikingly, a common phenotype of acute interstitial nephropathy was observed in 22 patients (median estimated glomerular filtration rate at presentation of 22 mL/min/1.73 m 2 (range 0–56)). Kidney biopsies showed polymorphic inflammatory cell infiltration (predominantly CD3 + T-cells, most of them demonstrating positive phospho- STAT3 staining) and non-necrotic granuloma in six cases. Immune-mediated glomerulopathy only or in combination with acute interstitial nephropathy was identified in eight patients. Next-generation sequencing ( n = 13) identified a major T-cell clone representing more than 1% of the T-cell population in all but two patients. None had a mutation of STAT3 . Twenty patients (69%) had two or more extra-kidney autoimmune diseases. Acute interstitial nephropathies were controlled with corticosteroids, cyclosporin A, or tofacitinib. Thus, we showed that small-sized T-cell clones (i.e., without lymphocytosis) undetectable without specific screening are associated with various immune kidney disorders, including a previously unrecognized phenotype characterized by severe inflammatory kidney fibrosis and lymphocytic JAK/STAT activation.
Keywords	immunoclones ; large granular lymphocytic leukemia ; renal fibrosis ; T-cell receptor ; STAT3 ; autoimmune disorders ; Medicine ; R
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cancer Stem Cells of Differentiated B-Cell Malignancies

Jean-Jacques Fournie / Anne Quillet-Mary / Loic Ysebaert / Emilie Gross / Guy Laurent

Cancers, Vol 3, Iss 2, Pp 1566-

Models and Consequences

2011 Volume 1579

Abstract: The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of ... ...

Abstract	The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a “top-to-bottom” clonal hierarchy from memory B-cells and a “bottom-to-top” model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity.
Keywords	cancer stem cell ; B-Lymphoma ; multiple myeloma ; B-CLL ; differentiated B malignancy ; memory B cell ; reprogramming ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2011-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A French multicentric prospective prognostic cohort with epidemiological, clinical, biological and treatment information to improve knowledge on lymphoma patients

Hervé Ghesquières / Cédric Rossi / Fanny Cherblanc / Sandra Le Guyader-Peyrou / Fontanet Bijou / Pierre Sujobert / Pascale Fabbro-Peray / Adeline Bernier / Aurélien Belot / Loic Chartier / Luc-Matthieu Fornecker / Isabelle Baldi / Krimo Bouabdallah / Camille Laurent / Lucie Oberic / Nadine Morineau / Steven Le Gouill / Franck Morschhauser / Corinne Haioun /

Gandhi Damaj / Stéphanie Guidez / Gaëlle Labouré / Olivier Fitoussi / Laure Lebras / Rémy Gressin / Gilles Salles / Loïc Ysebaert / Alain Monnereau

BMC Public Health, Vol 21, Iss 1, Pp 1-

study protocol of the “REal world dAta in LYmphoma and survival in adults” (REALYSA) cohort

2021 Volume 15

Abstract: Abstract 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 ... ...

Abstract	Abstract 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 5 years. 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 6 months in the first 3 years 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 .
Keywords	Cohort study ; Outcomes ; Lymphoma patients ; Real life ; France ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Antiviral Treatment of HCV-Infected Patients with B-Cell Non-Hodgkin Lymphoma

Laurent Alric / Caroline Besson / Nathanael Lapidus / Juliette Jeannel / Jean-Marie Michot / Patrice Cacoub / Danielle Canioni / Stanislas Pol / Frédéric Davi / Pascaline Rabiega / Loic Ysebaert / Delphine Bonnet / Olivier Hermine

PLoS ONE, Vol 11, Iss 10, p e

ANRS HC-13 Lympho-C Study.

2016 Volume 0162965

Abstract: Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted.First, ... ...

Abstract	Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted.First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL. In a second series, interferon-free regimens using a newly optimal combination therapy with direct-acting antiviral drugs (DAAs) were evaluated in 10 patients with HCV and B-NHL.The main lymphoma type was diffuse large B-cell lymphoma (38%) followed by marginal zone lymphoma (31%). In the multivariate analysis, patients with B-NHL treated by Peg-IFN-based therapy exhibited a greater SVR rate compared with controls, 50.8% vs 30.8%, respectively, p<0.01, odds ratio (OR) = 11.2 [2.3, 52.8]. B-NHL response was better (p = 0.02) in patients with SVR (69%) than in patients without SVR (31%). Premature discontinuation of Peg-IFN-based therapy was significantly more frequent in the B-NHL group (19.6%) compared with the control group (6.3%), p<0.02. Overall, survival was significantly enhanced in the controls than in the B-NHL group (hazard ratio = 34.4 [3.9, 304.2], p< 0.01). Using DAAs, SVR was achieved in 9/10 patients (90%). DAAs were both well tolerated and markedly efficient.The virologic response of HCV-associated B-NHL is high. Our study provides a comprehensive evaluation of different strategies for the antiviral treatment of B-NHL associated with HCV infection.
Keywords	Medicine ; R ; Science ; Q
Subject code	610 ; 616
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ribavirin for Chronic Hepatitis Prevention among Patients with Hematologic Malignancies

Suzanne Tavitian / Jean-Marie Peron / Françoise Huguet / Nassim Kamar / Florence Abravanel / Odile Beyne-Rauzy / Lucie Oberic / Stanislas Faguer / Laurent Alric / Murielle Roussel / Clément Gaudin / Loïc Ysebaert / Anne Huynh / Christian Recher

Emerging Infectious Diseases, Vol 21, Iss 8, Pp 1466-

2015 Volume 1469

Abstract: Findings among a cohort of 26 patients who had hematologic malignancies and hepatitis E virus (HEV) infection support that HEV can induce chronic hepatitis. However, a 3-month course of ribavirin can induce a rapid viral clearance, reducing the risk for ... ...

Abstract	Findings among a cohort of 26 patients who had hematologic malignancies and hepatitis E virus (HEV) infection support that HEV can induce chronic hepatitis. However, a 3-month course of ribavirin can induce a rapid viral clearance, reducing the risk for chronic hepatitis and enabling continuation of cytotoxic treatments for underlying malignancies.
Keywords	Hepatitis E ; hematology ; malignancy ; chronic hepatitis ; cirrhosis ; ribavirin ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2015-08-01T00:00:00Z
Publisher	Centers for Disease Control and Prevention
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A New alpha5beta1 integrin-dependent survival pathway through GSK3beta activation in leukemic cells.

Fabienne De Toni-Costes / Mathieu Despeaux / Jessica Bertrand / Ezzeddine Bourogaa / Loïc Ysebaert / Bernard Payrastre / Claire Racaud-Sultan

PLoS ONE, Vol 5, Iss 3, p e

2010 Volume 9807

Abstract: Cell survival mediated by integrin engagement has been implicated in cell adhesion-mediated drug resistance. We have recently demonstrated that the activation of glycogen synthase kinase 3 beta (GSK3beta) is a new pathway supporting the chemoresistance ... ...

Abstract	Cell survival mediated by integrin engagement has been implicated in cell adhesion-mediated drug resistance. We have recently demonstrated that the activation of glycogen synthase kinase 3 beta (GSK3beta) is a new pathway supporting the chemoresistance of leukemic cells adhered to fibronectin.We show here that in conditions of serum starvation, the fibronectin receptor alpha(5)beta(1) integrin, but not alpha(4)beta(1), induced activation of GSK3beta through Ser-9 dephosphorylation in adherent U937 cells. The GSK3beta-dependent survival pathway occurred in adherent leukemic cells from patients but not in the HL-60 and KG1 cell lines. In adhesion, activated GSK3beta was found in the cytosol/plasma membrane compartment and was co-immunoprecipitated with alpha(5) integrin, the phosphatase PP2A and the scaffolding protein RACK1. PP2A and its regulatory subunit B' regulated the Ser-9 phosphorylation of GSK3beta. In adherent leukemic cells, alpha(5)beta(1) integrin but not alpha(4)beta(1) upregulated the resistance to TNFalpha-induced apoptosis. Both extrinsic and intrinsic apoptotic pathways were under the control of alpha(5)beta(1) and GSK3beta.Our data show that, upon serum starvation, alpha(5)beta(1) integrin engagement could regulate specific pro-survival functions through the activation of GSK3beta.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2010-03-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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