Équipe
Eric Delabesse

ALTFAL :

Altération des facteurs de transcription dans

les leucémies aigües

Les spécificités
de notre axe de recherche

 

Les leucémies aiguës sont des cancers de la moelle osseuse associés à un mauvais pronostic, principalement sporadiques, certaines ont une origine génétique. Le développement de ces cancers fait suite à l’acquisition successive de mutations, (généralement entre 1 à 5).

Nous analysons les mécanismes biologiques par lesquels les mutations des gènes centraux de l’hématopoïèse (principalement PAX5 dans la différenciation B, GATA2 dans la différenciation myéloïde et USP7 et CHK1 acteurs du cycle cellulaire) reprogramment les progéniteurs normaux pour établir un état pré-leucémique et initier cette transformation leucémique. Notre équipe utilise une approche multidisciplinaire sur des échantillons de patients et des modèles murins, utilisant de la mutagenèse par technologie CRISPR-Cas9, des tests fonctionnels ex vivo et in vivo, de la cytométrie en flux, des analyses du transcriptome et des mutations (par séquençage de nouvelle génération) et du criblage à haut débit de médicaments.

Cette approche combinée nous permet d’étudier le développement hématopoïétique normal et la biologie des cellules souches hématopoïétiques ainsi que la reprogrammation oncogénique et le processus oncogénique induits par ces mutants.

Ces travaux s’intègre ainsi dans une recherche fondamentale et translationnelle, ayant pour perspective l’identification de nouveaux agents thérapeutiques améliorant le traitement de la leucémie aiguë, en particulier le ciblage des cellules souches leucémiques.

Recherche clinique

Syndromes myélodysplasiques

Leucémies Aiguës Myéloïdes B

Facteur de transcription GATA2

mutations germinales

registre national

DES PROJETS
DE RECHERCHE

PRODUCTIONS SCIENTIFIQUES

PUBLICATIONS 2021
Singh, Preeti, Maninder Heer, Anastasia Resteu, Aneta Mikulasova, Mojgan Reza, Laetitia Largeaud, Stephanie Dufrechou, et al. “GATA2 Deficiency Phenotype Associated with Tandem Duplication GATA2 and Over-Expression of GATA2-AS1.” Blood Advances, October 12, 2021, bloodadvances.2021005217. https://doi.org/10.1182/bloodadvances.2021005217.
Lafage-Pochitaloff, Marina, Bastien Gerby, Véronique Baccini, Laetitia Largeaud, Vincent Fregona, Nais Prade, Pierre-Yves Juvin, et al. “The CADM1 Tumor Suppressor Gene Is a Major Candidate Gene in MDS with Deletion of the Long Arm of Chromosome 11.” Blood Advances, October 12, 2021, bloodadvances.2021005311. https://doi.org/10.1182/bloodadvances.2021005311.
Magnol, Marion, Loukianos Couvaras, Yannick Degboé, Eric Delabesse, Cristina Bulai-Livideanu, Adeline Ruyssen-Witrand, and Arnaud Constantin. “VEXAS Syndrome in a Patient with Previous Spondyloarthritis with a Favourable Response to Intravenous Immunoglobulin and Anti-IL17 Therapy.” Rheumatology (Oxford, England) 60, no. 9 (September 1, 2021): e314–15. https://doi.org/10.1093/rheumatology/keab211.
Bouvier, Anne, Jean-François Hamel, Jacques Delaunay, Eric Delabesse, Pierre-Yves Dumas, Marie-Pierre Ledoux, Pierre Peterlin, et al. “Molecular Classification and Prognosis in Younger Adults with Acute Myeloid Leukemia and Intermediate-Risk Cytogenetics Treated or Not by Gemtuzumab Ozogamycin: Final Results of the GOELAMS/FILO Acute Myeloid Leukemia 2006-Intermediate-Risk Trial.” European Journal of Haematology 107, no. 1 (July 2021): 111–21. https://doi.org/10.1111/ejh.13626.
Largeaud, Laetitia, Pascale Cornillet-Lefebvre, Jean-François Hamel, Pierre-Yves Dumas, Naïs Prade, Stéphanie Dufrechou, Julien Plenecassagnes, et al. “Lomustine Is Beneficial to Older AML with ELN2017 Adverse Risk Profile and Intermediate Karyotype: A FILO Study.” Leukemia 35, no. 5 (May 2021): 1291–1300. https://doi.org/10.1038/s41375-020-01031-1.
Duployez, Nicolas, Laura A. Jamrog, Vincent Fregona, Camille Hamelle, Laurène Fenwarth, Sophie Lejeune, Nathalie Helevaut, et al. “Germline PAX5 Mutation Predisposes to Familial B-Cell Precursor Acute Lymphoblastic Leukemia.” Blood 137, no. 10 (March 11, 2021): 1424–28. https://doi.org/10.1182/blood.2020005756.
Cartel, Maëlle, Pierre-Luc Mouchel, Mathilde Gotanègre, Laure David, Sarah Bertoli, Véronique Mansat-De Mas, Arnaud Besson, Jean-Emmanuel Sarry, Stéphane Manenti, and Christine Didier. “Inhibition of Ubiquitin-Specific Protease 7 Sensitizes Acute Myeloid Leukemia to Chemotherapy.” Leukemia 35, no. 2 (February 2021): 417–32. https://doi.org/10.1038/s41375-020-0878-x.
PUBLICATIONS 2020
Bories, Pierre, Naïs Prade, Stéphanie Lagarde, Bastien Cabarrou, Laetitia Largeaud, Julien Plenecassagnes, Isabelle Luquet, et al. “Impact of TP53 Mutations in Acute Myeloid Leukemia Patients Treated with Azacitidine.” Edited by Francesco Bertolini. PLOS ONE 15, no. 10 (October 1, 2020): e0238795. https://doi.org/10.1371/journal.pone.0238795.
Dumas, Pierre-Yves, Sarah Bertoli, Emilie Bérard, Thibaut Leguay, Suzanne Tavitian, Jean Galtier, Camille Alric, et al. “Delivering HDAC over 3 or 5 Days as Consolidation in AML Impacts Health Care Resource Consumption but Not Outcome.” Blood Advances 4, no. 16 (August 25, 2020): 3840–49. https://doi.org/10.1182/bloodadvances.2020002511.
Fagnan, Alexandre, Frederik Otzen Bagger, Maria-Riera Piqué-Borràs, Cathy Ignacimouttou, Alexis Caulier, Cécile K. Lopez, Elie Robert, et al. “Human Erythroleukemia Genetics and Transcriptomes Identify Master Transcription Factors as Functional Disease Drivers.” Blood 136, no. 6 (August 6, 2020): 698–714. https://doi.org/10.1182/blood.2019003062.
Rohmer, Julien, Amélie Couteau‐Chardon, Julie Trichereau, Kewin Panel, Cyrielle Gesquiere, Raouf Ben Abdelali, Audrey Bidet, et al. “Epidemiology, Clinical Picture and Long‐term Outcomes of FIP1L1‐PDGFRA‐positive Myeloid Neoplasm with Eosinophilia: Data from 151 Patients.” American Journal of Hematology, July 28, 2020, ajh.25945. https://doi.org/10.1002/ajh.25945.
Dumas, Pierre-Yves, Sarah Bertoli, Emilie Bérard, Laetitia Largeaud, Audrey Bidet, Eric Delabesse, Thibaut Leguay, et al. “Real-World Outcomes of Patients with Refractory or Relapsed FLT3-ITD Acute Myeloid Leukemia: A Toulouse-Bordeaux DATAML Registry Study.” Cancers 12, no. 8 (July 24, 2020): 2044. https://doi.org/10.3390/cancers12082044.
Laurent, Anouchka P., Aurélie Siret, Cathy Ignacimouttou, Kunjal Panchal, M’Boyba Diop, Silvia Jenni, Yi-Chien Tsai, et al. “Constitutive Activation of RAS/MAPK Pathway Cooperates with Trisomy 21 and Is Therapeutically Exploitable in Down Syndrome B-Cell Leukemia.” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research 26, no. 13 (July 1, 2020): 3307–18. https://doi.org/10.1158/1078-0432.CCR-19-3519.
Gerby, Bastien, and Trang Hoang. “A Targetable Cue in T-Cell Malignancy.” Blood 135, no. 19 (May 7, 2020): 1616–17. https://doi.org/10.1182/blood.2020005142.
Vergez, François, Marie-Laure Nicolau-Travers, Sarah Bertoli, Jean-Baptiste Rieu, Suzanne Tavitian, Pierre Bories, Isabelle Luquet, et al. “CD34+CD38−CD123+ Leukemic Stem Cell Frequency Predicts Outcome in Older Acute Myeloid Leukemia Patients Treated by Intensive Chemotherapy but Not Hypomethylating Agents.” Cancers 12, no. 5 (May 6, 2020): 1174. https://doi.org/10.3390/cancers12051174.
Bertoli, Sarah, Pierre-Yves Dumas, Emilie Bérard, Laetitia Largeaud, Audrey Bidet, Eric Delabesse, Suzanne Tavitian, et al. “Outcome of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia before Second-Generation FLT3 Tyrosine Kinase Inhibitors: A Toulouse–Bordeaux DATAML Registry Study.” Cancers 12, no. 4 (March 25, 2020): 773. https://doi.org/10.3390/cancers12040773.
Bertoli, Sarah, Suzanne Tavitian, Emilie Bérard, Véronique Mansat-De Mas, Laetitia Largeaud, Noémie Gadaud, Jean-Baptiste Rieu, et al. “More than Ten Percent of Relapses Occur after Five Years in AML Patients with NPM1 Mutation.” Leukemia & Lymphoma, February 5, 2020, 1–4. https://doi.org/10.1080/10428194.2019.1706733.
Beziat, Guillaume, Suzanne Tavitian, Sarah Bertoli, Françoise Huguet, Laetitia Largeaud, Isabelle Luquet, François Vergez, et al. “Dactinomycin in Acute Myeloid Leukemia with NPM1 Mutations.” European Journal of Haematology 105, no. 3 (2020): 302–7. https://doi.org/10.1111/ejh.13438.
PUBLICATIONS 2019
Péricart, Sarah, Charlotte Waysse, Aurore Siegfried, Stephanie Struski, Eric Delabesse, Camille Laurent, and Solène Evrard. “Subsequent Development of Histiocytic Sarcoma and Follicular Lymphoma: Cytogenetics and next-Generation Sequencing Analyses Provide Evidence for Transdifferentiation of Early Common Lymphoid Precursor-a Case Report and Review of Literature.” Virchows Archiv: An International Journal of Pathology, December 5, 2019. https://doi.org/10.1007/s00428-019-02691-w.
Lopez, Cecile K., Esteve Noguera, Vaia Stavropoulou, Elie Robert, Zakia Aid, Paola Ballerini, Chrystele Bilhou-Nabera, et al. “Ontogenic Changes in Hematopoietic Hierarchy Determine Pediatric Specificity and Disease Phenotype in Fusion Oncogene-Driven Myeloid Leukemia.” Cancer Discovery, October 29, 2019. https://doi.org/10.1158/2159-8290.CD-18-1463.
Largeaud, Laetitia, Sarah Bertoli, Emilie Bérard, Stéphanie Dufrechou, Naïs Prade, Noémie Gadaud, Suzanne Tavitian, et al. “Outcome of Relapsed/Refractory AML Patients with IDH1R132 Mutations in Real Life before the Era of IDH1 Inhibitors.” Leukemia & Lymphoma, September 30, 2019, 1–4. https://doi.org/10.1080/10428194.2019.1668937.
Bertoli, Sarah, Suzanne Tavitian, Pierre Bories, Isabelle Luquet, Eric Delabesse, Thibault Comont, Audrey Sarry, Françoise Huguet, Emilie Bérard, and Christian Récher. “Outcome of Patients Aged 60-75 Years with Newly Diagnosed Secondary Acute Myeloid Leukemia: A Single-Institution Experience.” Cancer Medicine, June 7, 2019. https://doi.org/10.1002/cam4.2020.
Comont, T., K. Delavigne, P. Cougoul, S. Bertoli, E. Delabesse, P. Fenaux, and O. Beyne-Rauzy. “[Management of myelodysplastic syndromes in 2019: An update].” La Revue De Medecine Interne, May 1, 2019. https://doi.org/10.1016/j.revmed.2019.04.001.
Largeaud, Laetitia, Emilie Bérard, Sarah Bertoli, Stéphanie Dufrechou, Naïs Prade, Noémie Gadaud, Suzanne Tavitian, et al. “Outcome of AML Patients with IDH2 Mutations in Real World before the Era of IDH2 Inhibitors.” Leukemia Research 81 (April 27, 2019): 82–87. https://doi.org/10.1016/j.leukres.2019.04.010.
De Barros, Sandra, Flora Vayr, Fabien Despas, Mathilde Strumia, Clémentine Podevin, Martin Gauthier, Eric Delabesse, et al. “The Impact of Chronic Myeloid Leukemia on Employment: The French Prospective Study.” Annals of Hematology 98, no. 3 (March 2019): 615–23. https://doi.org/10.1007/s00277-018-3549-5.
Bertoli, Sarah, Etienne Paubelle, Emilie Bérard, Estelle Saland, Xavier Thomas, Suzanne Tavitian, Marie-Virginie Larcher, et al. “Ferritin Heavy/Light Chain (FTH1/FTL) Expression, Serum Ferritin Levels, and Their Functional as Well as Prognostic Roles in Acute Myeloid Leukemia.” European Journal of Haematology 102, no. 2 (February 2019): 131–42. https://doi.org/10.1111/ejh.13183.
Passet, Marie, Nicolas Boissel, François Sigaux, Colombe Saillard, Mario Bargetzi, Ibrahima Ba, Xavier Thomas, et al. “PAX5 P80R Mutation Identifies a Novel Subtype of B-Cell Precursor Acute Lymphoblastic Leukemia with Favorable Outcome.” Blood 133, no. 3 (17 2019): 280–84. https://doi.org/10.1182/blood-2018-10-882142.
Fournier, Benjamin, Estelle Balducci, Nicolas Duployez, Emmanuelle Clappier, Wendy Cuccuini, Chloé Arfeuille, Aurélie Caye-Eude, et al. “B-ALL With t(5;14)(Q31;Q32); IGH-IL3 Rearrangement and Eosinophilia: A Comprehensive Analysis of a Peculiar IGH-Rearranged B-ALL.” Frontiers in Oncology 9 (2019): 1374. https://doi.org/10.3389/fonc.2019.01374.

LES MEMBRES DE L’ÉQUIPE

Stéphanie Dufréchou
Personnel hospitalier / Hospital Staff
Christine Didier
Chercheur / Researcher
Naïs Prade
Personnel hospitalier / Hospital Staff
Marlène Pasquet
Enseignant-chercheur / Teacher-researcher
Esmaa Sellam
Etudiant ou stagiaire / PhD student and Trainee
Stéphanie Struski
Personnel hospitalier / Hospital Staff
Mathieu Bouttier
Ingénieur ou technicien / Engineer and Technician
Eric Delabesse
Enseignant-chercheur / Teacher-researcher
Christel Lauer
Ingénieur ou technicien / Engineer and Technician
Cyril Broccardo
Chercheur / Researcher
Sylvie Hebrard
Ingénieur ou technicien / Engineer and Technician
Bastien Gerby
Chercheur / Researcher
Camille Hamelle
Ingénieur ou technicien / Engineer and Technician
Manon Bayet
Etudiant ou stagiaire / PhD student and Trainee

LES PARTENAIRES & FINANCIERS

Centre de Recherches en Cancérologie de Toulouse

Centre de Recherches en Cancérologie de Toulouse (Oncopole)

Toulouse - FR

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05 82 74 15 75

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