المؤلفون: Iat, Alexandre, Loschi, Michael, Benachour, Sami, Calleja, Anne, Chiche, Edmond, Sudaka, Isabelle, Aquaronne, Danièle, Ferrero, Corinne, Fenwarth, Laurène, Marceau, Alice, Fournier, Elise, Dadone‐Montaudie, Berengere, Cluzeau, Thomas

المصدر: Cancer Medicine ; volume 13, issue 6 ; ISSN 2045-7634 2045-7634

الوصف: Background of the study AML classification tools have been developed to stratify the risk at AML diagnosis. There is a need to evaluate these tools in the current therapeutic era. Cohort characteristics In this retrospective study, we compared five classifiers: ELN 2017, ELN 2022, ALFA classifier, Papaemmanuil et al. classifier, and Lindsley et al. classifier, in a real‐life cohort of 281 patients newly diagnosed for AML in Nice University Hospital. In our cohort median age was 68 years old, sex ratio was M/F 56%/44%, performance status was lower than 2 in 73.1% of patients, AML subtype was “De novo” in 71.5%, “secondary” in 22.4%, and “therapy‐related” in 6.0% of patients. Intensive chemotherapy was used in 53.0% of patients, and non‐intensive chemotherapy in 40.6% of patients. Molecular analysis was available in a large majority of patients and the main mutations found were NPM1 (22.7%), DNMT3A (17.4%), TP53 (13.1%), TET2 (12.4%), and FLT3‐ITD (12.4%). Results In our findings, the comparison of overall survival between the three prognostic groups in the global cohort was statistically significant in all classifiers: ELN 2017 p < 0.0001, ELN 2022 p < 0.0001, ALFA classifier p < 0.0001, Papaemmanuil classifier p < 0.0001, Lindsley classifier p = 0.001. ELN 2017, ELN 2022, ALFA classifier, Papaemmanuil classifier, and Lindsley classifier were calculated respectively in 99%, 99%, 89%, 90%, and 89% of patients. Conclusions Using Akaike’s information criteria (AIC) to compare all five classifiers, ELN 2022 is the best classifier into younger and older patients and for prognosis.

الإتاحة: https://doi.org/10.1002/cam4.7103Test

المؤلفون: Marceau, Alice

مرشدي الرسالة: Lille 2, Preudhomme, Claude

مصطلحات موضوعية: Leucémie aiguë myeloïde, Biologie moléculaire, Séquençage haut débit, Pronostic, Myeloid leukemia, Molecular biology, High flow sequencing, Prognostic

الوصف: Malgré une amélioration de la prise en charge thérapeutique au cours des dernières années, les leucémies aiguës myéloïdes (LAM) pédiatriques sont des hémopathies graves, avec des taux de rechute pouvant atteindre 30% et des taux de survie inférieurs à 75%. Une meilleure description des anomalies moléculaires chez les enfants atteints de LAM est nécessaire pour affiner le pronostic de ces patients. En utilisant le séquençage haut débit ciblé sur 36 gènes et la technique de LD (ligation-dependent) RT-PCR, ce travail décrit le profil moléculaire ainsi que sa signification pronostique chez 385 enfants atteints de LAM de novo inclus dans l’essai clinique prospectif ELAM02. 76 % des patients présentent au moins une mutation parmi les gènes étudiés. Les mutations les plus fréquentes concernent les gènes contrôlant les voies de signalisation des tyrosine kinases (61 %), suivis par les facteurs de transcription (16 %), les suppresseurs de tumeurs (14 %), les modificateurs de la chromatine (9 %), la méthylation de l'ADN (8 %), la cohésine (5 %) et le spliceosome (3 %). De plus, un transcrit de fusion est détecté dans près de la moitié des cas. Au final, les réarrangements impliquant le CBF, les mutations de NPM1 et double-mutations de CEBPA (CEBPA-dm) représentent 37% de la cohorte et définissent un sous-groupe moléculaire au pronostic favorable (survie globale à 3 ans: 92,1%) alors que les fusions impliquant NUP98, les mutations WT1, RUNX1 et PHF6 (15% de la cohorte) constituent un sous-groupe moléculaire au pronostic péjoratif (survie globale à 3 ans: 46,1%). Les réarrangements de KMT2A (21 % de la cohorte) sont associés à un risque intermédiaire. Malgré quelques similitudes, le profil moléculaire et sa signification pronostique diffèrent entre les LAM de l’enfant et de l’adulte. Ces résultats contribuent à affiner la stratification du risque pronostique des LAM pédiatriques et ainsi améliorer leur prise en charge thérapeutique. Cette classification moléculaire reste à valider dans d’autres cohortes pédiatriques indépendantes.
Despite major treatment improvements over the past decades, pediatric acute myeloid leukemia (AML) is still a life-threatening malignancy with relapse rates up to 30% and survival rates below 75%. A better description of the pattern of molecular aberrations in childhood AML is needed to refine prognostication in such patients. We report here the comprehensive molecular landscape using both high-throughput sequencing focused on 36 genes and ligation-dependent RT-PCR in 385 children with de novo AML enrolled in the prospective ELAM02 trial and we evaluated their prognostic significance. 76% of patients had at least one mutation among the genes we screened. The most common class of mutations involved genes that control kinase signaling (61%) followed by transcription factors (16%), tumor suppressors (14%), chromatin modifiers (9%), DNA methylation controllers (8%), cohesin genes (5%) and spliceosome (3%). Moreover, a recurrent transcript fusion was detected in about a half of pediatric patients. Overall, CBF rearrangements, NPM1 and double CEBPA mutations represented 37% of the cohort and defined a favorable molecular subgroup (3-years overall survival: 92.1%) while NUP98 fusions, WT1, RUNX1 and PHF6 mutations (15% of the cohort) segregated into a poor molecular subgroup (3-years overall survival: 46.1%). KMT2A-rearrangements (21% of the cohort) were associated with an intermediate risk. Despite some overlaps, the spectrum of molecular aberrations and their prognostic significance differ between childhood and adult AML. These data have important implications to contribute in refining risk stratification of pediatric AML and show the need for further validations in independent pediatric cohorts.

الإتاحة: http://www.theses.fr/2018LIL2S003/documentTest

المؤلفون: Le Corre, Brieg, Marceau, Alice, Pantzas, Konstantinos, Combrié, Sylvain, Talenti, Francesco Rinaldo, Harouri, Abdelmounaim, Gérard, Bruno, Beaudoin, Grégoire, Gratiet, Luc Le, Patriarche, Gilles, de Rossi, Alfredo, Léger, Yoan, Sagnes, Isabelle, Grisard, Arnaud

المساهمون: Centre de Nanosciences et de Nanotechnologies (C2N), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Thales Research and Technology Palaiseau, THALES France, Dipartimento di Ingegneria dell'Informazione, Elettronica e Telecomunicazioni Roma (DIET), Università degli Studi di Roma "La Sapienza" = Sapienza University Rome (UNIROMA), Alcatel-Thales III-V Lab (III-V Lab ), Institut des Fonctions Optiques pour les Technologies de l'informatiON (FOTON), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Nationale Supérieure des Sciences Appliquées et de Technologie (ENSSAT)-Centre National de la Recherche Scientifique (CNRS), ANR-17-CE24-0019,ORPHEUS,Phénomènes optiques du second ordre dans les microdisques de phosphure de gallium intégrés sur silicium(2017), ANR-22-PEEL-0005,OFCOC,Optical Frequency Combs On a Chip(2022), European Project: 814147

المصدر: Journées Nationales d'Optique Guidée (JNOG'40) ; https://hal.science/hal-04196334Test ; Journées Nationales d'Optique Guidée (JNOG'40), Jul 2023, Lyon, France

مصطلحات موضوعية: Guide d’onde suspendu, Phosphure de gallium, Optique non-linéaire, [PHYS]Physics [physics]

جغرافية الموضوع: Lyon, France

الوصف: International audience

العلاقة: info:eu-repo/grantAgreement//814147/EU/European Union’s Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie grant agreement No. 814147/; hal-04196334; https://hal.science/hal-04196334Test; https://hal.science/hal-04196334/documentTest; https://hal.science/hal-04196334/file/JNOG_OPGaP_BLC.pdfTest

الإتاحة: https://hal.science/hal-04196334Test
https://hal.science/hal-04196334/documentTest
https://hal.science/hal-04196334/file/JNOG_OPGaP_BLC.pdfTest

المؤلفون: Calleja, Anne, Loschi, Michael, Bailly, Laurent, Morisot, Adeline, Marceau, Alice, Mannone, Lionel, Robert, Guillaume, Auberger, Patrick, Preudhomme, Claude, Raynaud, Sophie, Subtil, Fabien, Sujobert, Pierre, Cluzeau, Thomas

المساهمون: Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service de Biostatistiques Lyon, Hospices Civils de Lyon (HCL)

المصدر: ISSN: 2045-7634.

مصطلحات موضوعية: [SDV]Life Sciences [q-bio]

الوصف: International audience

العلاقة: hal-04179587; https://hal.science/hal-04179587Test; https://hal.science/hal-04179587/documentTest; https://hal.science/hal-04179587/file/CAM4-12-5656.pdfTest; PUBMEDCENTRAL: PMC10028034

الإتاحة: https://doi.org/10.1002/cam4.5408Test
https://hal.science/hal-04179587Test
https://hal.science/hal-04179587/documentTest
https://hal.science/hal-04179587/file/CAM4-12-5656.pdfTest

المؤلفون: Calleja, Anne, Loschi, Michael, Bailly, Laurent, Morisot, Adeline, Marceau, Alice, Mannone, Lionel, Robert, Guillaume, Auberger, Patrick, Preudhomme, Claude, Raynaud, Sophie, Subtil, Fabien, Sujobert, Pierre, Cluzeau, Thomas

المصدر: Cancer Medicine ; volume 12, issue 5, page 5656-5660 ; ISSN 2045-7634 2045-7634

الوصف: Personalized medicine is a challenge for patients with acute myeloid leukemia (AML). The identification of several genetic mutations in several AML trials led to the creation of a personalized prognostic scoring algorithm known as the Knowledge Bank (KB). In this study, we assessed the prognostic value of this algorithm on a cohort of 167 real life AML patients. We compared KB predicted outcomes to real‐life outcomes. For patients younger than 60‐year‐old, OS was similar in favorable and intermediate ELN risk category. However, KB algorithm failed to predict OS for younger patients in the adverse ELN risk category and for patients older than 60 years old in the favorable ELN risk category. These discrepancies may be explained by the emergence of several new therapeutic options as well as the improvement of allogeneic stem cell transplantation (aHSCT) outcomes and supportive cares. Personalized medicine is a major challenge and predictions models are powerful tools to predict patient's outcome. However, the addition of new therapeutic options in the field of AML requires a prospective validation of these scoring systems to include recent therapeutic innovations.

الإتاحة: https://doi.org/10.1002/cam4.5408Test

المؤلفون: Heiblig, Mael, Duployez, Nicolas, Marceau, Alice, Lebon, Delphine, Goursaud, Laure, Plantier, Isabelle, Stalnikiewich, Laure, Cambier, Nathalie, Balsat, Marie, Fossard, Gaelle, Labussiere, Helene, Barraco, Fiorenza, Ducastelle, Sophie, Sujobert, Pierre, Huet, Sarah, Hayette, Sandrine, Ghesquieres, Herve, Thomas, Xavier, Preudhomme, Claude

المساهمون: Centre Hospitalier Lyon Sud CHU - HCL (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), 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 CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), 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 d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre Hospitalier de Roubaix, Service d'hématologie clinique CH Lens, Centre Hospitalier de Lens, Centre hospitalier Valenciennes, Nord

المصدر: ISSN: 2072-6694.

مصطلحات موضوعية: DNMT3A, NPM1, acute myeloid leukemia, elderly, prognosis, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Simple Summary DNMT3A mutation has been associated with adverse outcomes. In this study, we aimed to investigate the impact of DNMT3A status on NPM1 MRD predictive value for survival in a retrospective cohort of acute myeloid leukemia (AML) patients aged over 60 years old treated intensively. A total of 138 patients treated for NPM1-mutated AML in two French institutions were analyzed retrospectively. A 4log reduction of NPM1 MRD was associated with a better outcome. DNMT3A negative patients who achieved a 4log reduction had a superior outcome to those who did not. However, postinduction NPM1 MRD1 reduction was not predictive of OS and LFS in DNMT3Amut patients. These results confirm that post-induction NPM1 MRD1 is a reliable tool to assess disease outcome in elderly AML patients. However, the presence of DNMT3A also identify a subgroup of patients at high risk of relapse. Minimal residual disease (MRD) is now a powerful surrogate marker to assess the response to chemotherapy in acute myeloid leukemia (AML). DNMT3A mutation has been associated with adverse outcomes. In this study, we aimed to investigate the impact of DNMT3A status on NPM1 MRD predictive value for survival in a retrospective cohort of AML patients aged over 60 years old treated intensively. A total of 138 patients treated for NPM1-mutated AML in two French institutions were analyzed retrospectively. DNMT3A status did not influence the probability of having a >= 4log MRD1 reduction after induction. Only 20.4% of FLT3-ITD patients reached >= 4log MRD1 reduction compared to 47.5% in FLT3wt cases. A 4log reduction of NPM1 MRD was associated with a better outcome, even in FLT3-ITD mutated patients, independent of the allelic ratio. DNMT3A negative patients who reached a 4log reduction had a superior outcome to those who did not (HR = 0.23; p < 0.001). However, postinduction NPM1 MRD1 reduction was not predictive of OS and LFS in DNMT3Amut patients. These results confirm that post-induction NPM1 MRD1 is a reliable ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33947035; hal-03606391; https://u-picardie.hal.science/hal-03606391Test; https://u-picardie.hal.science/hal-03606391/documentTest; https://u-picardie.hal.science/hal-03606391/file/cancers-13-02156-v3.pdfTest; PUBMED: 33947035; PUBMEDCENTRAL: PMC8124973

الإتاحة: https://doi.org/10.3390/cancers13092156Test
https://u-picardie.hal.science/hal-03606391Test
https://u-picardie.hal.science/hal-03606391/documentTest
https://u-picardie.hal.science/hal-03606391/file/cancers-13-02156-v3.pdfTest

المؤلفون: Marceau, Alice, Combrié, Sylvain, Ghorbel, Inès, Sagnes, Isabelle, De Rossi, Alfredo, Panzas, Konstantinos, Grisard, Arnaud

المصدر: 2023 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC)

الإتاحة: https://doi.org/10.1109/cleo/europe-eqec57999.2023.10231458Test
http://xplorestaging.ieee.org/ielx7/10231377/10231353/10231458.pdf?arnumber=10231458Test

المؤلفون: Heiblig, Maël, Duployez, Nicolas, Marceau, Alice, Lebon, Delphine, Goursaud, Laure, Plantier, Isabelle, Stalnikiewich, Laure, Cambier, Nathalie, Balsat, Marie, Fossard, Gaelle, Labussiere-Wallet, Helene, Barraco, Fiorenza, Ducastelle-Lepretre, Sophie, Sujobert, Pierre, Huet, Sarah, Hayette, Sandrine, Ghesquieres, Herve, Thomas, Xavier, Preudhomme, Claude

المساهمون: Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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 CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de 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), Etablissement français du sang Rennes (EFS Bretagne), Service d'hématologie, Centre Hospitalier de Roubaix, Centre hospitalier Valenciennes, Nord, Centre Hospitalier Lyon Sud CHU - HCL (CHLS), Service d’Hématologie Centre Hospitalier Lyon Sud - HCL, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)

المصدر: ISSN: 0006-4971.

مصطلحات موضوعية: DNMT3A, NPM1, acute myeloid leukemia, elderly, prognosis, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Minimal residual disease (MRD) is now a powerful surrogate marker to assess the response to chemotherapy in acute myeloid leukemia (AML). DNMT3A mutation has been associated with adverse outcomes. In this study, we aimed to investigate the impact of DNMT3A status on NPM1 MRD predictive value for survival in a retrospective cohort of AML patients aged over 60 years old treated intensively. A total of 138 patients treated for NPM1-mutated AML in two French institutions were analyzed retrospectively. DNMT3A status did not influence the probability of having a ≥ 4log MRD1 reduction after induction. Only 20.4% of FLT3-ITD patients reached ≥ 4log MRD1 reduction compared to 47.5% in FLT3wt cases. A 4log reduction of NPM1 MRD was associated with a better outcome, even in FLT3-ITD mutated patients, independent of the allelic ratio. DNMT3A negative patients who reached a 4log reduction had a superior outcome to those who did not (HR = 0.23; p < 0.001). However, postinduction NPM1 MRD1 reduction was not predictive of OS and LFS in DNMT3Amut patients. These results confirm that post-induction NPM1 MRD1 is a reliable tool to assess disease outcome in elderly AML patients. However, the presence of DNMT3A also identifies a subgroup of patients at high risk of relapse.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33947035; hal-03606389; https://u-picardie.hal.science/hal-03606389Test; https://u-picardie.hal.science/hal-03606389/documentTest; https://u-picardie.hal.science/hal-03606389/file/main.pdfTest; PUBMED: 33947035; PUBMEDCENTRAL: PMC8124973

الإتاحة: https://doi.org/10.1182/blood-2020-141890Test
https://u-picardie.hal.science/hal-03606389Test
https://u-picardie.hal.science/hal-03606389/documentTest
https://u-picardie.hal.science/hal-03606389/file/main.pdfTest

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

المصدر: Leukemia Research Reports ; volume 13, page 100202 ; ISSN 2213-0489

مصطلحات موضوعية: Oncology, Hematology

الإتاحة: https://doi.org/10.1016/j.lrr.2020.100202Test
https://api.elsevier.com/content/article/PII:S221304892030008X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S221304892030008X?httpAccept=text/plainTest

المؤلفون: Drevon, Louis, Marceau, Alice, Maarek, Odile, Cuccuini, Wendy, Clappier, Emmanuelle, Eclache, Virginie, Cluzeau, Thomas, Richez, Valentine, Berkaoui, Inès, Dimicoli‐Salazar, Sophie, Bidet, Audrey, Vial, Jean‐Philippe, Park, Sophie, Vieira Dos Santos, Christina, Kaphan, Eléonore, Berthon, Céline, Stamatoullas, Aspasia, Delhommeau, François, Abermil, Nassera, Braun, Thorsten, Sapena, Rosa, Lusina, Daniel, Renneville, Aline, Adès, Lionel, Raynaud, Sophie, Fenaux, Pierre

المصدر: British Journal of Haematology ; volume 182, issue 6, page 843-850 ; ISSN 0007-1048 1365-2141

الوصف: Summary Isolated trisomy 8 (+8) is a frequent cytogenetic abnormality in the myelodysplastic syndromes ( MDS ), but its characteristics are poorly reported. We performed a retrospective study of 138 MDS patients with isolated +8, classified or reclassified as MDS (excluding MDS /myeloproliferative neoplasm). Myeloproliferative ( MP ) features were defined by the repeated presence of one of the following: white blood cell count >10 × 10 9 /l, myelemia (presence of circulating immature granulocytes with a predominance of more mature forms) >2%, palpable splenomegaly. Fifty‐four patients (39·1%) had MP features: 28 at diagnosis, 26 were acquired during evolution. MP forms had more EZH 2 (33·3% vs. 12·0% in non‐ MP , P = 0·047), ASXL 1 (66·7% vs. 42·3%, P = 0·048) and STAG 2 mutations (77·8% vs. 21·7%, P = 0·006). Median event‐free survival (EFS) and overall survival ( OS ) were 25 and 27 months for patients with MP features at diagnosis, versus 28 ( P = 0·15) and 39 months ( P = 0·085) for those without MP features, respectively. Among the 57 patients who received hypomethylating agent ( HMA ), OS was lower in MP cases (13 months vs. 23 months in non‐ MP cases, P = 0.02). In conclusion, MP features are frequent in MDS with isolated +8. MP forms had more EZH 2 , ASXL 1 and STAG 2 mutations, responded poorly to HMA , and tended to have poorer survival than non‐ MP forms.

الإتاحة: https://doi.org/10.1111/bjh.15490Test