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1. STIM2 is involved in the regulation of apoptosis and the cell cycle in normal and malignant monocytic cells

Author

Stefan Djordjevic, Raphaël Itzykson, Frédéric Hague, Delphine Lebon, Julien Legrand, Hakim Ouled‐Haddou, Guillaume Jedraszak, Juliette Harbonnier, Louison Collet, Etienne Paubelle, Jean‐Pierre Marolleau, Loïc Garçon, and Thomas Boyer

Subjects
apoptosis, calcium, genomic stress, leukemia, monocytic cells, SOCE, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Calcium is a ubiquitous messenger that regulates a wide range of cellular functions, but its involvement in the pathophysiology of acute myeloid leukemia (AML) is not widely investigated. Here, we identified, from an analysis of The Cancer Genome Atlas and genotype‐tissue expression databases, stromal interaction molecule 2 (STIM2) as being highly expressed in AML with monocytic differentiation and negatively correlated with overall survival. This was confirmed on a validation cohort of 407 AML patients. We then investigated the role of STIM2 in cell proliferation, differentiation, and survival in two leukemic cell lines with monocytic potential and in normal hematopoietic stem cells. STIM2 expression increased at the RNA and protein levels upon monocyte differentiation. Phenotypically, STIM2 knockdown drastically inhibited cell proliferation and induced genomic stress with DNA double‐strand breaks, as shown by increased levels of phosphorylate histone H2AXγ (p‐H2AXγ), followed by activation of the cellular tumor antigen p53 pathway, decreased expression of cell cycle regulators such as cyclin‐dependent kinase 1 (CDK1)–cyclin B1 and M‐phase inducer phosphatase 3 (CDC25c), and a decreased apoptosis threshold with a low antiapoptotic/proapoptotic protein ratio. Our study reports STIM2 as a new actor regulating genomic stability and p53 response in terms of cell cycle and apoptosis of human normal and malignant monocytic cells.

Published
2024
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3. Myeloid-Derived Suppressor Cells in Bladder Cancer: An Emerging Target

Author

Clément Klein, Samy Mebroukine, Mathilde Madéry, Alexandra Moisand, Thomas Boyer, Nicolas Larmonier, Grégoire Robert, and Charlotte Domblides

Subjects
myeloid-derived suppressor cells, bladder cancer, tumor microenvironment, immune inhibition, biomarker, immunotherapy, Cytology, QH573-671
Abstract

Bladder cancer remains a prevalent and challenging malignancy. Myeloid-derived suppressor cells (MDSCs) have emerged as key contributors to the immunosuppressive tumor microenvironment, facilitating tumor progression, immune evasion, and resistance to therapies. This review explores the role of MDSC in bladder cancer, highlighting their involvement in immune regulation; tumor progression; and resistance to therapies such as bacillus Calmette–Guérin (BCG) therapy, chemotherapy, and immune checkpoint inhibitors (ICIs). We also discuss their potential as biomarkers and therapeutic targets, with current evidence suggesting that targeting MDSCs, either alone or in combination with existing treatments such as BCG and ICIs, may enhance anti-tumor immunity and improve clinical outcomes. However,, challenges remain, particularly regarding the identification and therapeutic modulation of MDSC subpopulations. Further research is warranted to fully elucidate their role in bladder cancer and to optimize MDSC-targeted therapies.

Published
2024
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4. THBS1+ myeloid cells expand in SLD hepatocellular carcinoma and contribute to immunosuppression and unfavorable prognosis through TREM1

Author

Julie Giraud, Domitille Chalopin, Eloïse Ramel, Thomas Boyer, Atika Zouine, Marie-Alix Derieppe, Nicolas Larmonier, Olivier Adotevi, Brigitte Le Bail, Jean-Frédéric Blanc, Christophe Laurent, Laurence Chiche, Marc Derive, Macha Nikolski, and Maya Saleh

Subjects
CP: Cancer, Biology (General), QH301-705.5
Abstract

Summary: Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral or non-viral etiologies including steatotic liver diseases (SLDs). Expansion of immunosuppressive myeloid cells is a hallmark of inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance. Here, we present a high-resolution atlas of innate immune cells from patients with HCC that unravels an SLD-associated contexture characterized by influx of inflammatory and immunosuppressive myeloid cells, including a discrete population of THBS1+ regulatory myeloid (Mreg) cells expressing monocyte- and neutrophil-affiliated genes. THBS1+ Mreg cells expand in SLD-associated HCC, populate fibrotic lesions, and are associated with poor prognosis. THBS1+ Mreg cells are CD163+ but distinguished from macrophages by high expression of triggering receptor expressed on myeloid cells 1 (TREM1), which contributes to their immunosuppressive activity and promotes HCC tumor growth in vivo. Our data support myeloid subset-targeted immunotherapies to treat HCC.

Published
2024
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6. Artificial intelligence to empower diagnosis of myelodysplastic syndromes by multiparametric flow cytometry

Author

Valentin Clichet, Delphine Lebon, Nicolas Chapuis, Jaja Zhu, Valérie Bardet, Jean-Pierre Marolleau, Loïc Garçon, Alexis Caulier, and Thomas Boyer

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

The diagnosis of myelodysplastic syndromes (MDS) might be challenging and relies on the convergence of cytological, cytogenetic, and molecular factors. Multiparametric flow cytometry (MFC) helps diagnose MDS, especially when other features do not contribute to the decision-making process, but its usefulness remains underestimated, mostly due to a lack of standardization of cytometers. We present here an innovative model integrating artificial intelligence (AI) with MFC to improve the diagnosis and the classification of MDS. We develop a machine learning model through an elasticnet algorithm directed on a cohort of 191 patients, only based on flow cytometry parameters selected by the Boruta algorithm, to build a simple but reliable prediction score with five parameters. Our AI-assisted MDS prediction score greatly improves the sensitivity of the Ogata score while keeping an excellent specificity validated on an external cohort of 89 patients with an Area Under the Curve of 0.935. This model allows the diagnosis of both high- and low-risk MDS with 91.8% sensitivity and 92.5% specificity. Interestingly, it highlights a progressive evolution of the score from clonal hematopoiesis of indeterminate potential (CHIP) to highrisk MDS, suggesting a linear evolution between these different stages. By significantly decreasing the overall misclassification of 52% for patients with MDS and of 31.3% for those without MDS (P=0.02), our AI-assisted prediction score outperforms the Ogata score and positions itself as a reliable tool to help diagnose MDS.

Published
2023
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7. Hormone Receptor Signaling and Breast Cancer Resistance to Anti-Tumor Immunity

Author

Alexandra Moisand, Mathilde Madéry, Thomas Boyer, Charlotte Domblides, Céline Blaye, and Nicolas Larmonier

Subjects
hormone receptors, estrogen receptors, hormone signaling, breast cancers, cancer immunity, immunotherapies, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Breast cancers regroup many heterogeneous diseases unevenly responding to currently available therapies. Approximately 70–80% of breast cancers express hormone (estrogen or progesterone) receptors. Patients with these hormone-dependent breast malignancies benefit from therapies targeting endocrine pathways. Nevertheless, metastatic disease remains a major challenge despite available treatments, and relapses frequently ensue. By improving patient survival and quality of life, cancer immunotherapies have sparked considerable enthusiasm and hope in the last decade but have led to only limited success in breast cancers. In addition, only patients with hormone-independent breast cancers seem to benefit from these immune-based approaches. The present review examines and discusses the current literature related to the role of hormone receptor signaling (specifically, an estrogen receptor) and the impact of its modulation on the sensitivity of breast cancer cells to the effector mechanisms of anti-tumor immune responses and on the capability of breast cancers to escape from protective anti-cancer immunity. Future research prospects related to the possibility of promoting the efficacy of immune-based interventions using hormone therapy agents are considered.

Published
2023
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8. Combining imaging flow cytometry and machine learning for high-throughput schistocyte quantification: A SVM classifier development and external validation cohort

Author

Julien Demagny, Camille Roussel, Maïlys Le Guyader, Eric Guiheneuf, Véronique Harrivel, Thomas Boyer, Momar Diouf, Michaël Dussiot, Yohann Demont, and Loïc Garçon

Subjects
Schistocyte, Imaging flow cytometry, Machine learning, Thrombotic microangiopathy, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Schistocyte counts are a cornerstone of the diagnosis of thrombotic microangiopathy syndrome (TMA). Their manual quantification is complex and alternative automated methods suffer from pitfalls that limit their use. We report a method combining imaging flow cytometry (IFC) and artificial intelligence for the direct label-free and operator-independent quantification of schistocytes in whole blood. Methods: We used 135,045 IFC images from blood acquisition among 14 patients to extract 188 features with IDEAS® software and 128 features from a convolutional neural network (CNN) with Keras framework in order to train a support vector machine (SVM) blood elements’ classifier used for schistocytes quantification. Finding: Keras features showed better accuracy (94.03%, CI: 93.75-94.31%) than ideas features (91.54%, CI: 91.21-91.87%) in recognising whole-blood elements, and together they showed the best accuracy (95.64%, CI: 95.39-95.88%). We obtained an excellent correlation (0.93, CI: 0.90-0.96) between three haematologists and our method on a cohort of 102 patient samples. All patients with schistocytosis (>1% schistocytes) were detected with excellent specificity (91.3%, CI: 82.0-96.7%) and sensitivity (100%, CI: 89.4-100.0%). We confirmed these results with a similar specificity (91.1%, CI: 78.8-97.5%) and sensitivity (100%, CI: 88.1-100.0%) on a validation cohort (n=74) analysed in an independent healthcare centre. Simultaneous analysis of 16 samples in both study centres showed a very good correlation between the 2 imaging flow cytometers (Y=1.001x). Interpretation: We demonstrate that IFC can represent a reliable tool for operator-independent schistocyte quantification with no pre-analytical processing which is of most importance in emergency situations such as TMA. Funding: None.

Published
2022
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9. Beyond Immunosuppression: The Multifaceted Functions of Tumor-Promoting Myeloid Cells in Breast Cancers

Author

Céline Blaye, Thomas Boyer, Florent Peyraud, Charlotte Domblides, and Nicolas Larmonier

Subjects
breast cancer, tumor-promoting myeloid cells, immunosuppression, immunotherapies, tumor microenvironment, Immunologic diseases. Allergy, RC581-607
Abstract

Breast cancers are commonly associated with an immunosuppressive microenvironment responsible for tumor escape from anti-cancer immunity. Cells of the myeloid lineage account for a major part of this tumor-promoting landscape. These myeloid cells are composed of heterogeneous subsets at different stages of differentiation and have traditionally been described by their cardinal ability to suppress innate and adaptive anticancer immunity. However, evidence has accumulated that, beyond their immunosuppressive properties, breast cancer-induced myeloid cells are also equipped with a broad array of “non-immunological” tumor-promoting functions. They therefore represent major impediments for anticancer therapies, particularly for immune-based interventions. We herein analyze and discuss current literature related to the versatile properties of the different myeloid cell subsets engaged in breast cancer development. We critically assess persisting difficulties and challenges in unequivocally discriminate dedicated subsets, which has so far prevented both the selective targeting of these immunosuppressive cells and their use as potential biomarkers. In this context, we propose the concept of IMCGL, “pro-tumoral immunosuppressive myeloid cells of the granulocytic lineage”, to more accurately reflect the contentious nature and origin of granulocytic cells in the breast tumor microenvironment. Future research prospects related to the role of this myeloid landscape in breast cancer are further considered.

Published
2022
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10. Stem Cells in Myelodysplastic Syndromes and Acute Myeloid Leukemia: First Cousins or Unrelated Entities?

Author

Romane Joudinaud and Thomas Boyer

Subjects
myelodysplastic syndromes, acute myeloid leukemia, leukemic stem cell, whole genome sequencing, single cell, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Myelodysplastic syndromes (MDSs) are associated with a significant risk of transformation to acute myeloid leukemia (AML), supported by alterations affecting malignant stem cells. This review focuses on the metabolic, phenotypic and genetic characteristics underlying this dynamic evolution, from myelodysplastic stem cells (MDS-SCs) to leukemic stem cells (LSCs). MDS-SCs are more likely to be derived from healthy hematopoietic stem cells (HSCs), whereas LSCs may originate from healthy progenitors, mostly LMPP (lymphoid-primed multipotential progenitors). Moreover, overexpression of CD123 and CLL1 markers by LSCs and MDS-SCs in high risk-MDS [HR-MDS] has led to exciting therapeutic applications. Single-cell sequencing has suggested that clonal evolution in the stem cell compartment was non-linear during MDS initiation and progression to AML, with pre-MDS-SC acquiring distinct additional mutations in parallel, that drive either MDS blast production or AML transformation. In AML and HR-MDS, common metabolic alterations have been identified in malignant stem cells, including activation of the protein machinery and dependence on oxidative phosphorylation. Targeting these metabolic abnormalities could prevent HR-MDS from progressing to AML. Strikingly, in low risk-MDS-SC, the expression of ribosomal proteins is decreased, which may be accompanied by a reduction in protein synthesis.

Published
2021
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12. Acute myeloid leukemia synchronous with multiple myeloma successfully treated by azacytidine/lenalidomide and daratumumab without a decrease in myeloid clone size

Author

Celine Berthon, Morgane Nudel, Eileen M. Boyle, Laure Goursaud, Thomas Boyer, Alice Marceau, and Bruno Quesnel

Subjects
Myeloma, AML, CMML, Azacytidine, Lenalidomide, Daratumumab, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Synchronous diagnosis of acute myeloid leukemia (AML) and symptomatic multiple myeloma (MM) is a rare situation that poses serious therapeutic difficulties. We report the case of a 68-year-old male which evolved simultaneously to symptomatic MM and AML. Both diseases first responded to treatment for 40 months after 7+3 induction and maintenance therapy of azacytidine + lenalidomide. MM relapsed first and was treated with azacytidine + daratumumab, which led an additional 15 months of progression-free survival. Little myeloid clonal size reduction over time was seen. This case shows that AML and MM can be effectively treated simultaneously using appropriate combinations.

Published
2020
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13. Influence of the Metabolism on Myeloid Cell Functions in Cancers: Clinical Perspectives

Author

Thomas Boyer, Céline Blaye, Nicolas Larmonier, and Charlotte Domblides

Subjects
metabolism, myeloid cells, macrophages, myeloid-derived suppressive cells, cancer, immunotherapy, Cytology, QH573-671
Abstract

Tumor metabolism plays a crucial role in sustaining tumorigenesis. There have been increasing reports regarding the role of tumor metabolism in the control of immune cell functions, generating a potent immunosuppressive contexture that can lead to immune escape. The metabolic reprogramming of tumor cells and the immune escape are two major hallmarks of cancer, with several instances of crosstalk between them. In this paper, we review the effects of tumor metabolism on immune cells, focusing on myeloid cells due to their important role in tumorigenesis and immunosuppression from the early stages of the disease. We also discuss ways to target this specific crosstalk in cancer patients.

Published
2022
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14. Biomarkers of Gemtuzumab Ozogamicin Response for Acute Myeloid Leukemia Treatment

Author

Laurène Fenwarth, Elise Fournier, Meyling Cheok, Thomas Boyer, Fanny Gonzales, Sylvie Castaigne, Nicolas Boissel, Juliette Lambert, Hervé Dombret, Claude Preudhomme, and Nicolas Duployez

Subjects
acute myeloid leukemia, gemtuzumab ozogamicin, biomarkers, CD33, FLT3, therapy, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Gemtuzumab ozogamicin (GO, Mylotarg®) consists of a humanized CD33-targeted antibody-drug conjugated to a calicheamicin derivative. Growing evidence of GO efficacy in acute myeloid leukemia (AML), demonstrated by improved outcomes in CD33-positive AML patients across phase I to III clinical trials, led to the Food and Drug Administration (FDA) approval on 1 September 2017 in CD33-positive AML patients aged 2 years and older. Discrepancies in GO recipients outcome have raised significant efforts to characterize biomarkers predictive of GO response and have refined the subset of patients that may strongly benefit from GO. Among them, CD33 expression levels, favorable cytogenetics (t(8;21), inv(16)/t(16;16), t(15;17)) and molecular alterations, such as NPM1, FLT3-internal tandem duplications and other signaling mutations, represent well-known candidates. Additionally, in depth analyses including minimal residual disease monitoring, stemness expression (LSC17 score), mutations or single nucleotide polymorphisms in GO pathway genes (CD33, ABCB1) and molecular-derived scores, such as the recently set up CD33_PGx6_Score, represent promising markers to enhance GO response prediction and improve patient management.

Published
2020
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17. Linezolid induces ring sideroblasts

Author

Christophe Willekens, Florent Dumezy, Thomas Boyer, Aline Renneville, Julien Rossignol, Céline Berthon, Angélique Cotteau-Leroy, Lotfi Mehiaoui, Bruno Quesnel, and Claude Preudhomme

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2013
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18. Interpréter une théorie physique

Author

Thomas Boyer and Anouk Barberousse

Subjects
interpretation, meaning, physical theory, quantum mechanics, symbols, context, Philology. Linguistics, P1-1091
Abstract

Physical theories are nowadays very mathematized, and what scientists manipulate so as to describe, predict and control the phenomena, are (in part) equations, which consist in many mathematical symbols. These mathematical objects don't have any physical signification by themselves: they don't “speak” about the phenomena. An interpretation is required. In this article, we are interested in the interpretation which a physical theory needs so as to fulfill its role. We start by making explicit a traditional distinction: the “lean” interpretation (a simple instrument which allows the symbols of the theory to receive a physical meaning, strictly limited to the experimental results) differs from the “rich” interpretation (which makes up an image of the world compatible with the way the theory mathematically describes the experimental results). Our aim in this article is to show that this distinction should be amended. We rely on the example of Quantum Mechanics, but the distinction intends to be general, for any physical theory.

Published
2013
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20. Sustainable Aging in Aix-Marseille-Provence Metropolis: Assessment Indicators and Interactive Visualizations for Policy Making

Author

Perez, Joan, Alessandro, Araldi, Thomas, Boyer, Sébastien, Bridier, Fabrice, Decoupiny, Giovanni, Fusco, Vincent, Laperrière, Marie-Laure, Trémélo, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Gervasi, Osvaldo, editor, Murgante, Beniamino, editor, Rocha, Ana Maria A. C., editor, Garau, Chiara, editor, Scorza, Francesco, editor, Karaca, Yeliz, editor, and Torre, Carmelo M., editor

Published
2023
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24. Assisted Authoring of Model-Based Systems Engineering Documents

Author

Gomes, Ivan, Karban, Robert, Regalia, Blake, and Chammard, Thomas Boyer

Abstract

In systems engineering practices system design and analysis have historically been performed using a document-centric approach where stakeholders produce a number of documents that represent their views on a system under development. Given the ad-hoc, disparate, and informal nature of natural language documents, these views become quickly inconsistent. Rigor in engineering work is also lost in the transition from model based engineering design and analysis to engineering documents. Once the documents are delivered, the engineering portion of the work is disconnected. In the Open Model Based Engineering Environment (OpenMBEE), Cross-References (aka transclusions) synthesize data for engineering when the information is not simply hyperlinked, but referenced in place in a document, upgrading a document-based process with model-based engineering technology. Those Cross-References are nowadays partially created manually, putting a burden on the engineer who is authoring the document.This paper presents an approach which can assist the engineer by providing machine-generated suggestions for Cross-References using language processing, graph analysis, and clustering technologies on model data managed by the OpenMBEE infrastructure.

Published
2020

25. Supplementary Figure 3 from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience

Author

Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset

Abstract

Waffle chart (%) of patients addressed for cytopenia exploration after OC exposed to a PARPi treatment from cytopenia diagnosis (A) and cytopenia diagnosis based on NGS results (B). Dot plots (C) showing the median WBC, hemoglobin, and platelet counts from patients referred for cytopenia exploration after OC exposed to a PARPi treatment according to t-MN diagnosis (“t-MN”) or not (“Cytopenia”).

Published
2023

26. Supplementary Figure 2 from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience

Author

Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset

Abstract

Blood smear and bone marrow aspiration of patient referred for cytopenia post PARPi.

Published
2023

27. Supplementary Figure 4 from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience

Author

Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset

Abstract

Commutation plot visualizing the mutated genes in t-MN after OC according to PARPi treatment.

Published
2023

28. Supplementary Table 3 from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience

Author

Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset

Abstract

Univariate analysis for overall survival from t-MN diagnosis of patients from the national cohort.

Published
2023

29. Supplementary Figure 1 from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience

Author

Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset

Abstract

Flow chart of the study displaying the three cohorts.

Published
2023

30. Supplementary Table 2 from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience

Author

Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset

Abstract

TP53 mutations characteristics among t-MN PARPi national cohort.

Published
2023

31. Supplementary Table 1 from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience

Author

Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset

Abstract

Univariate analysis for overall survival from t-MN diagnosis of patients diagnosed with t-MN after OC according to PARPi exposure.

Published
2023

32. Data from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience

Author

Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset

Abstract

Purpose:To provide insights into the diagnosis and management of therapy-related myeloid neoplasms (t-MN) following PARP inhibitors (PARPi).Experimental Design:In a French cancer center, we identified and described the profiles of 13 t-MN diagnosed among 37 patients with ovarian cancer referred to hematology consultation for cytopenia under PARPi. Next, we described these 13 t-MN post-PARPi among 37 t-MN post ovarian cancer according to PARPi exposure. Finally, we described 69 t-MN post-PARPi in a national cohort.Results:From 2016 to 2021, cumulative incidence of t-MN was 3.5% (13/373) among patients with ovarian cancer treated with PARPi. At time of hematologic consultation, patients with t-MN had a longer PARPi exposure (9 vs. 3 months, P = 0.01), lower platelet count (74 vs. 173 G/L, P = 0.0005), and more cytopenias (2 vs. 1, P = 0.0005). Compared with t-MN not exposed to PARPi, patients with t-MN-PARPi had more BRCA1/2 germline mutation (61.5% vs. 0%, P = 0.03) but similar overall survival (OS). In the national cohort, most t-MN post-PARPi had a complex karyotype (61%) associated with a high rate of TP53 mutation (71%). Median OS was 9.6 months (interquartile range, 4–14.6). In multivariate analysis, a longer time between end of PARPi and t-MN (HR, 1.046; P = 0.02), olaparib compared with other PARPi (HR, 5.82; P = 0.003) and acute myeloid leukemia (HR, 2.485; P = 0.01) were associated with shorter OS.Conclusions:In a large series, we described a high incidence of t-MN post-PARPi associated with unfavorable cytogenetic and molecular abnormalities leading to poor OS. Early detection is crucial, particularly in cases of delayed cytopenia.

Published
2023

34. Machine learning identifies the independent role of dysplasia in the prediction of response to chemotherapy in AML

Author

Nicolas Freynet, Hervé Dombret, Daniel Lusina, Emmanuel Benayoun, Xavier Thomas, Estelle Guérin, Raphael Itzykson, Pascal Turlure, Claude Preudhomme, Laurène Fenwarth, Christine Terré, Aline Renneville, Elise Fournier, Thomas Boyer, Bouchra Badaoui, Isabel Garcia, Cécile Pautas, Thomas Cluzeau, Claude Gardin, Orianne Wagner-Ballon, Matthieu Duchmann, Juliette Lambert, Pierre Fenaux, Meyling Cheok, and Bruno Quesnel

Subjects
Adult, Male, Cancer Research, NPM1, medicine.medical_treatment, Antineoplastic Agents, Machine learning, computer.software_genre, Logistic regression, Machine Learning, medicine, Humans, Complete response, Aged, Chromosome 7 (human), Chemotherapy, business.industry, Myeloid leukemia, Hematology, Middle Aged, Prognosis, medicine.disease, Clinical trial, Leukemia, Myeloid, Acute, Treatment Outcome, Oncology, Dysplasia, Cytogenetic Analysis, Female, Artificial intelligence, business, Megakaryocytes, computer
Abstract

The independent prognostic impact of specific dysplastic features in acute myeloid leukemia (AML) remains controversial and may vary between genomic subtypes. We apply a machine learning framework to dissect the relative contribution of centrally reviewed dysplastic features and oncogenetics in 190 patients with de novo AML treated in ALFA clinical trials. One hundred and thirty-five (71%) patients achieved complete response after the first induction course (CR). Dysgranulopoiesis, dyserythropoiesis and dysmegakaryopoiesis were assessable in 84%, 83% and 63% patients, respectively. Multi-lineage dysplasia was present in 27% of assessable patients. Micromegakaryocytes (q = 0.01), hypolobulated megakaryocytes (q = 0.08) and hyposegmented granulocytes (q = 0.08) were associated with higher ELN-2017 risk. Using a supervised learning algorithm, the relative importance of morphological variables (34%) for the prediction of CR was higher than demographic (5%), clinical (2%), cytogenetic (25%), molecular (29%), and treatment (5%) variables. Though dysplasias had limited predictive impact on survival, a multivariate logistic regression identified the presence of hypolobulated megakaryocytes (p = 0.014) and micromegakaryocytes (p = 0.035) as predicting lower CR rates, independently of monosomy 7 (p = 0.013), TP53 (p = 0.004), and NPM1 mutations (p = 0.025). Assessment of these specific dysmegakarypoiesis traits, for which we identify a transcriptomic signature, may thus guide treatment allocation in AML.

Published
2021

35. TREM1+regulatory myeloid cells expand in steatohepatitis-HCC and associate with poor prognosis and therapeutic resistance to immune checkpoint blockade

Author

Julie Giraud, Domitille Chalopin, Eloïse Ramel, Thomas Boyer, Atika Zouine, Marie-Alix Derieppe, Nicolas Larmonier, Olivier Adotevi, Brigitte Le Bail, Jean-Frédéric Blanc, Laurence Chiche, Macha Nikolski, and Maya Saleh

Abstract

Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral and non-viral etiologies. Immune checkpoint blockade primarily benefits patients with viral HCC. Expansion of suppressive myeloid cells is a hallmark of chronic inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance in the steatohepatitis setting. Here, we present a high resolution atlas of hepatic innate immune cells from patients with HCC that unravels a steatohepatitis contexture characterized by the emergence of high entropy myeloid cell states and myeloid-biased NK cell differentiation. We identify a discrete population of tumor-infiltrating myeloid cells, predominant in the steatohepatitis setting, that expresses a variety of myeloid lineage-affiliated genes, including granulocyte, macrophage and dendritic cell features, and can be identified in HCC tumors based on selective dual expression ofTREM1andCD163. Functional characterization reveals that TREM1+CD163+myeloid cells highly express TGFβ and IL-13RA, localize to HCC fibrotic lesions, and potently suppress T cell effector functionsex vivo, a function further potentiated by TREM1 engagement. We refer to this population as TREM1+CD163+regulatory myeloid cells (TREM1+CD163+Mreg). Deconvolution analyses in large cohorts of patients with HCC and other solid tumors reveals that the density of TREM1+CD163+Mregincreases in advanced stages, associates with poor prognosis, and therapeutic resistance to PD-1 blockade. Our data support myeloid subset-targeted immunotherapies to treat HCC and identify TREM1 as a therapeutic target.HIGHLIGHTSAtlas of hepatic innate immune cells (100,000 transcriptomes) from patients with HCCCore signatures to identify, discriminate and localize innate lymphoid and myeloid cellsA population of TREM1+CD163+myeloid cells, referred to as TREM1+CD163+Mreg, expands in steatohepatitis HCCTREM1+CD163+Mregexpress granulocyte- and macrophage/dendritic cell-lineage genesTREM1+CD163+Mregpotently suppress T cell effector functions, which is potentiated by TREM1 engagement by cognate ligandsTREM1+CD163+Mregproduce high levels of TGFβ and populate fibrotic lesionsThe density of TREM1+CD163+Mregincreases in advanced HCC and associate with poor patient survivalThe density of TREM1+CD163+Mregassociates with resistance to immune checkpoint blockade in other solid tumors

Published
2022

37. HDAC6 regulates human erythroid differentiation through modulation of JAK2 signalling

Author

Pascal Vong, Kahia Messaoudi, Nicolas Jankovsky, Cathy Gomilla, Yohann Demont, Alexis Caulier, Guillaume Jedraszak, Julien Demagny, Stefan Djordjevic, Thomas Boyer, Jean Pierre Marolleau, Jacques Rochette, Hakim Ouled‐Haddou, and Loïc Garçon

Subjects
Molecular Medicine, Cell Biology
Abstract

Among histone deacetylases, HDAC6 is unusual in its cytoplasmic localization. Its inhibition leads to hyperacetylation of non-histone proteins, inhibiting cell cycle, proliferation and apoptosis. Ricolinostat (ACY-1215) is a selective inhibitor of the histone deacetylase HDAC6 with proven efficacy in the treatment of malignant diseases, but anaemia is one of the most frequent side effects. We investigated here the underlying mechanisms of this erythroid toxicity. We first confirmed that HDAC6 was strongly expressed at both RNA and protein levels in CD34

Published
2022

39. Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience

Author

Vincent Marmouset, Justine Decroocq, Sylvain Garciaz, Gabriel Etienne, Amine Belhabri, Sarah Bertoli, Lauris Gastaud, Celestine Simand, Sylvain Chantepie, Madalina Uzunov, Alexis Genthon, Celine Berthon, Edmond Chiche, Pierre-Yves Dumas, Jacques Vargaftig, Géraldine Salmeron, Emilie Lemasle, Emmanuelle Tavernier, Jeremy Delage, Marion Loirat, Nadine Morineau, Felix Blanc-Durand, Patricia Pautier, Veronique Vergé, Nathalie Auger, Myrtille Thomas, Laetitia Stefani, Marion Lepelley, Thomas Boyer, Sylvain Thepot, Marie-Pierre Gourin, Pascal Bourquard, Matthieu Duchmann, Pierre Morice, Mauricette Michallet, Lionel Ades, Pierre Fenaux, Christian Recher, Hervé Dombret, Arnaud Pages, Christophe Marzac, Alexandra Leary, Jean-Baptiste Micol, Université de Picardie Jules Verne (UPJV), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Aix Marseille Université (AMU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Bergonié [Bordeaux], UNICANCER, Centre Léon Bérard [Lyon], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], CHU Lille, Université Côte d'Azur - Faculté de Médecine (UCA Faculté Médecine), Université Côte d'Azur (UCA), BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique et Thérapie Cellulaire [CHU Bordeaux], Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CH de Saint-Nazaire, CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Ovarian Neoplasms, Cancer Research, Immunology, Neoplasms, Second Primary, Cell Biology, Hematology, Poly(ADP-ribose) Polymerase Inhibitors, Carcinoma, Ovarian Epithelial, Biochemistry, Oncology, Mutation, Humans, Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Germ-Line Mutation
Abstract

Purpose: To provide insights into the diagnosis and management of therapy-related myeloid neoplasms (t-MN) following PARP inhibitors (PARPi). Experimental Design: In a French cancer center, we identified and described the profiles of 13 t-MN diagnosed among 37 patients with ovarian cancer referred to hematology consultation for cytopenia under PARPi. Next, we described these 13 t-MN post-PARPi among 37 t-MN post ovarian cancer according to PARPi exposure. Finally, we described 69 t-MN post-PARPi in a national cohort. Results: From 2016 to 2021, cumulative incidence of t-MN was 3.5% (13/373) among patients with ovarian cancer treated with PARPi. At time of hematologic consultation, patients with t-MN had a longer PARPi exposure (9 vs. 3 months, P = 0.01), lower platelet count (74 vs. 173 G/L, P = 0.0005), and more cytopenias (2 vs. 1, P = 0.0005). Compared with t-MN not exposed to PARPi, patients with t-MN-PARPi had more BRCA1/2 germline mutation (61.5% vs. 0%, P = 0.03) but similar overall survival (OS). In the national cohort, most t-MN post-PARPi had a complex karyotype (61%) associated with a high rate of TP53 mutation (71%). Median OS was 9.6 months (interquartile range, 4–14.6). In multivariate analysis, a longer time between end of PARPi and t-MN (HR, 1.046; P = 0.02), olaparib compared with other PARPi (HR, 5.82; P = 0.003) and acute myeloid leukemia (HR, 2.485; P = 0.01) were associated with shorter OS. Conclusions: In a large series, we described a high incidence of t-MN post-PARPi associated with unfavorable cytogenetic and molecular abnormalities leading to poor OS. Early detection is crucial, particularly in cases of delayed cytopenia.

Published
2022

41. Disease escape with the selective loss of the Philadelphia chromosome after tyrosine kinase inhibitor exposure in Ph-positive acute lymphoblastic leukemia

Author

Nicolas Gazeau, Catherine Roche-Lestienne, Valérie Coiteux, Nicolas Duployez, Coralie Derrieux, Bruno Quesnel, Céline Berthon, Claude Preudhomme, Laure Goursaud, Thomas Boyer, Florent Dumezy, Nathalie Grardel, and Olivier Nibourel

Subjects
Cancer Research, medicine.medical_specialty, business.industry, medicine.drug_class, Cytogenetics, Hematology, Disease, Philadelphia chromosome, medicine.disease, Tyrosine-kinase inhibitor, Oncology, Ph-positive acute lymphoblastic leukemia, medicine, Cancer research, Acute lymphocytic leukaemia, business
Published
2020

43. Familial myeloid malignancies with germline TET2 mutation

Author

Laure Goursaud, Bruno Quesnel, Céline Berthon, David Beauvais, Catherine Roche-Lestienne, Laurène Fenwarth, Nicolas Duployez, Guillemette Huet, Nathalie Cambier, Claude Preudhomme, Claire Bories, Olivier Nibourel, Elise Fournier, Thomas Boyer, and Alice Marceau-Renaut

Subjects
Cancer Research, Myeloid, business.industry, medicine.medical_treatment, Hematology, Hematopoietic stem cell transplantation, medicine.disease, Germline, Lymphoma, Frameshift mutation, Leukemia, medicine.anatomical_structure, Germline mutation, Oncology, Mutation (genetic algorithm), medicine, Cancer research, business
Published
2019

44. Influence of the Metabolism on Myeloid Cell Functions in Cancers: Clinical Perspectives

Author

Thomas Boyer, Céline Blaye, Nicolas Larmonier, and Charlotte Domblides

Subjects
QH301-705.5, Neoplasms, Tumor Microenvironment, cancer, Humans, myeloid-derived suppressive cells, Myeloid Cells, General Medicine, Immunotherapy, Biology (General), metabolism, macrophages
Abstract

Tumor metabolism plays a crucial role in sustaining tumorigenesis. There have been increasing reports regarding the role of tumor metabolism in the control of immune cell functions, generating a potent immunosuppressive contexture that can lead to immune escape. The metabolic reprogramming of tumor cells and the immune escape are two major hallmarks of cancer, with several instances of crosstalk between them. In this paper, we review the effects of tumor metabolism on immune cells, focusing on myeloid cells due to their important role in tumorigenesis and immunosuppression from the early stages of the disease. We also discuss ways to target this specific crosstalk in cancer patients.

Published
2021

45. Beyond Immunosuppression: The Multifaceted Functions of Tumor-Promoting Myeloid Cells in Breast Cancers

Author

Céline Blaye, Thomas Boyer, Florent Peyraud, Charlotte Domblides, and Nicolas Larmonier

Subjects
Immunosuppression Therapy, Immunology, Immunologic Deficiency Syndromes, Tumor Microenvironment, Immunology and Allergy, Humans, Breast Neoplasms, Female, Myeloid Cells, Tumor Escape, Immunotherapy
Abstract

Breast cancers are commonly associated with an immunosuppressive microenvironment responsible for tumor escape from anti-cancer immunity. Cells of the myeloid lineage account for a major part of this tumor-promoting landscape. These myeloid cells are composed of heterogeneous subsets at different stages of differentiation and have traditionally been described by their cardinal ability to suppress innate and adaptive anticancer immunity. However, evidence has accumulated that, beyond their immunosuppressive properties, breast cancer-induced myeloid cells are also equipped with a broad array of “non-immunological” tumor-promoting functions. They therefore represent major impediments for anticancer therapies, particularly for immune-based interventions. We herein analyze and discuss current literature related to the versatile properties of the different myeloid cell subsets engaged in breast cancer development. We critically assess persisting difficulties and challenges in unequivocally discriminate dedicated subsets, which has so far prevented both the selective targeting of these immunosuppressive cells and their use as potential biomarkers. In this context, we propose the concept of IMCGL, “pro-tumoral immunosuppressive myeloid cells of the granulocytic lineage”, to more accurately reflect the contentious nature and origin of granulocytic cells in the breast tumor microenvironment. Future research prospects related to the role of this myeloid landscape in breast cancer are further considered.

Published
2021

46. Accurate classification of plasma cell dyscrasias is achieved by combining artificial intelligence and flow cytometry

Author

Loïc Garçon, Delphine Lebon, Véronique Harrivel, Murielle Gautier, François Vergez, Deborah Assouan, Pierre Morel, Valentin Clichet, Thomas Matthes, Marie Beaumont, Thomas Boyer, Caroline Delette, Jean-Pierre Marolleau, Eric Guiheneuf, Alexis Caulier, and Lavinia Merlusca

Subjects
Male, Paraproteinemias, Plasma cell, Monoclonal Gammopathy of Undetermined Significance, Flow cytometry, Unknown Significance, immune system diseases, Artificial Intelligence, hemic and lymphatic diseases, medicine, Humans, Diagnosis, Computer-Assisted, Multiple myeloma, Aged, Retrospective Studies, medicine.diagnostic_test, Cluster of differentiation, business.industry, Hematology, medicine.disease, Flow Cytometry, Monoclonal gammopathy, medicine.anatomical_structure, Female, Artificial intelligence, medicine.symptom, business, Multiple Myeloma, Monoclonal gammopathy of undetermined significance
Abstract

Monoclonal gammopathy of unknown significance (MGUS), smouldering multiple myeloma (SMM), and multiple myeloma (MM) are very common neoplasms. However, it is often difficult to distinguish between these entities. In the present study, we aimed to classify the most powerful markers that could improve diagnosis by multiparametric flow cytometry (MFC). The present study included 348 patients based on two independent cohorts. We first assessed how representative the data were in the discovery cohort (123 MM, 97 MGUS) and then analysed their respective plasma cell (PC) phenotype in order to obtain a set of correlations with a hypersphere visualisation. Cluster of differentiation (CD)27 and CD38 were differentially expressed in MGUS and MM (P < 0·001). We found by a gradient boosting machine method that the percentage of abnormal PCs and the ratio PC/CD117 positive precursors were the most influential parameters at diagnosis to distinguish MGUS and MM. Finally, we designed a decisional algorithm allowing a predictive classification ≥95% when PC dyscrasias were suspected, without any misclassification between MGUS and SMM. We validated this algorithm in an independent cohort of PC dyscrasias (n = 87 MM, n = 41 MGUS). This artificial intelligence model is freely available online as a diagnostic tool application website for all MFC centers worldwide (https://aihematology.shinyapps.io/PCdyscrasiasToolDg/).

Published
2021

47. Poly(ADP‐ribose)polymerase inhibitors‐associated myeloid neoplasms: a retrospective study from the French Network of Pharmacovigilance centres

Author

Fanny Rocher, Marion Allouchery, Raoul Herbrecht, Danièle Aquaronne, Nathalie Massy, Hélène Peyrouzet, Julien Mahé, Martine Alt-Tebacher, Charles Dolladille, Kevin Bihan, Christine Le Beller, Louise Gaboriau, Brahim Azzouz, Basile Chrétien, Pierre-Marie Morice, Thomas Boyer, Anthony Sourisseau, Sylvain Chantepie, Marion Lepelley, Joachim Alexandre, Alexis Genthon, Laetitia Stefani, Célestine Simand, Ghada Miremont, Vieillissement, Fragilité (VIEFRA - EA 3797), and Université de Reims Champagne-Ardenne (URCA)

Subjects
Male, 2019-20 coronavirus outbreak, Myeloid, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Poly(ADP-ribose) Polymerase Inhibitors, Poly (ADP-Ribose) Polymerase Inhibitor, Pharmacovigilance, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, 030304 developmental biology, 0303 health sciences, Myeloproliferative Disorders, business.industry, Neoplasms, Second Primary, Retrospective cohort study, Hematology, Virology, 3. Good health, Cross-Sectional Studies, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, France, business
Abstract

International audience

Published
2021

48. Explaining Scientific Collaboration: A General Functional Account

Author

Thomas Boyer-Kassem, Cyrille Imbert, Archives Henri-Poincaré - Philosophie et Recherches sur les Sciences et les Technologies (AHP-PReST), Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Pazzaglia, Nicolas, Métaphysique allemande et philosophie pratique (MAPP), and Université de Poitiers

Subjects
History, [SHS.PHIL]Humanities and Social Sciences/Philosophy, Complex system, 06 humanities and the arts, Minor (academic), 0603 philosophy, ethics and religion, Epistemology, [SHS]Humanities and Social Sciences, [SHS.HISPHILSO]Humanities and Social Sciences/History, Philosophy and Sociology of Sciences, [SHS.PHIL] Humanities and Social Sciences/Philosophy, Philosophy, History and Philosophy of Science, [SHS.HISPHILSO] Humanities and Social Sciences/History, Philosophy and Sociology of Sciences, 060302 philosophy, Scientific Collaboration + Functional explanation, [SHS] Humanities and Social Sciences, Sociology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; Scientific collaboration has been increasing over the past two centuries, a fact for which various explanations have been proposed. We offer a novel functional explanation of this increase in collaboration, grounded in a sequential model of scientific research where the priority rule applies. Robust patterns concerning the differential successfulness of collaborative groups with respect to their competitors are derived, and it is argued that these patterns feed the development of collaboration. This general mechanism may trigger an 'arms race' and is compatible with a certain amount of decrease in the productivity of collaborative groups as well as some over-collaboration. The proposed explanation succeeds in integrating various factors usually associated with the rise of collaboration.

Published
2021

49. Hereditary Predisposition to Acute Myeloid Leukemia in Older Adults

Author

Claude Preudhomme, Delphine Lebon, Jean-Pierre Marolleau, Thomas Boyer, Elise Fournier, Laure Goursaud, Alice Marceau-Renaut, Laurène Fenwarth, Nicolas Duployez, Alexis Caulier, Céline Berthon, Emma Lachaier, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Picardie Jules Verne (UPJV), Etablissement français du sang [Rennes] (EFS Bretagne), Hôpital Claude Huriez [Lille], and DESSAIVRE, Louise

Subjects
Oncology, medicine.medical_specialty, business.industry, lcsh:RC633-647.5, [SDV]Life Sciences [q-bio], MEDLINE, Myeloid leukemia, Case Report, Hematology, lcsh:Diseases of the blood and blood-forming organs, [SDV] Life Sciences [q-bio], Text mining, Internal medicine, medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2021

50. A simple score (Biovid-19) based on biological parameters predicts transfer to intensive care units and death in COVID-19 patients

Author

Guillaume Couillez, Julien Maizel, Thomas Boyer, Jean-Luc Schmit, Ophélie Evrard, Etienne Brochot, Alexis Caulier, Catherine François, Rémy Nyga, Chloé Sauzay, Claire Andrejak, Sandrine Castelain, Loïc Garçon, Maïlys Le Guyader, DESSAIVRE, Louise, WEB Architecture x Semantic WEB x WEB of Data (WEB3), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Parasitologie-Mycologie [CHRU LIlle], Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Virologie [CHU Amiens], Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), and Laboratoire d'Hématologie [CHU Amiens]

Subjects
Adult, Male, Patient Transfer, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Risk Assessment, Severity of Illness Index, General Biochemistry, Genetics and Molecular Biology, Cohort Studies, Young Adult, Intensive care, Transfer (computing), Severity of illness, medicine, Humans, Hospital Mortality, Patient transfer, Letter to the Editor, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, business.industry, SARS-CoV-2, Sodium, COVID-19, Retrospective cohort study, General Medicine, Middle Aged, Prognosis, Triage, Death, [SDV] Life Sciences [q-bio], Intensive Care Units, Research Design, Emergency medicine, Potassium, Female, France, business, Biomarkers, Blood Chemical Analysis, Cohort study
Abstract

International audience; No abstract available

Published
2021

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