Titre :

Midostaurin shapes macroclonal and microclonal evolution of FLT3-mutated acute myeloid leukemia

Auteur(s) :

Joudinaud, Romane [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Boudry, Augustin [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Fenwarth, Laurène [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Geffroy, Sandrine [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Salson, Mikaël [Auteur]
Bioinformatics and Sequence Analysis [BONSAI]
Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 [CRIStAL]
Dombret, Hervé [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex- Institut Universitaire Hématologie-IUH) [IRSL]
Berthon, Celine [Auteur]
Service des Maladies du Sang [CHU Lille] [SMS]
Hôpital Claude Huriez [Lille]
Pigneux, Arnaud [Auteur]
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Lebon, Delphine [Auteur]
HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 [HEMATIM]
CHU Amiens-Picardie
Peterlin, Pierre [Auteur]
Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers [CRCI2NA ]
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital [CHU Nantes]
Bouzy, Simon [Auteur]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Flandrin-Gresta, Pascale [Auteur]
Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] [CHU ST-E]
Tavernier, Emmanuelle [Auteur]
Institut de Cancérologie de la Loire Lucien Neuwirth
Carre, Martin [Auteur]
Centre Hospitalier Universitaire [CHU Grenoble] [CHUGA]
Tondeur, Sylvie [Auteur]
Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] [CHU ST-E]
Haddaoui, Lamya [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Itzykson, Raphaël [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Génomes, biologie cellulaire et thérapeutiques [GenCellDis (U944 / UMR7212)]
Bertoli, Sarah [Auteur]
Centre de Recherches en Cancérologie de Toulouse [CRCT]
Institut Universitaire du Cancer de Toulouse - Oncopole [IUCT Oncopole - UMR 1037]
Bidet, Audrey [Auteur]
Delabesse, Eric [Auteur]
Service Hématologie - IUCT-Oncopole [CHU Toulouse]
Hunault, Mathilde [Auteur]
Récher, Christan [Auteur]
Preudhomme, Claude [Auteur]
Duployez, Nicolas [Auteur]
Dumas, Pierre-Yves [Auteur]

Titre de la revue :

Blood advances

Éditeur :

The American Society of Hematology

Date de publication :

2024-10-17

ISSN :

2473-9529

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hématologie

Résumé en anglais : [en]

Despite the use of midostaurin (MIDO) with intensive chemotherapy (ICT) as the front-line treatment for FLT3-mutated acute myeloid leukemia (AML), complete remission rates are close to 60-70%, and relapses occur in over ...
Lire la suite >Despite the use of midostaurin (MIDO) with intensive chemotherapy (ICT) as the front-line treatment for FLT3-mutated acute myeloid leukemia (AML), complete remission rates are close to 60-70%, and relapses occur in over 40% of cases. Here we studied the molecular mechanisms underlying refractory/relapsed (R/R) situation in FLT3-mutated AML patients. We conducted a retrospective and multicenter study involving 150 patients with R/R AML harboring FLT3-ITD (n=130) and/or FLT3-TKD (n=26) at diagnosis assessed by standard methods. Patients were treated in front-line with ICT + MIDO (n=54) or ICT alone (n=96) according to the diagnosis date and label of MIDO. The evolution of FLT3 clones and co-mutations was analyzed in paired diagnosis-R/R samples by targeted high-throughput sequencing. Using a dedicated algorithm for FLT3-ITD detection, 189 FLT3-ITD microclones (allelic ratio [AR] < 0.05) and 225 macroclones (AR ≥ 0.05) were detected at both time points. At R/R disease, the rate of FLT3-ITD persistence was lower in patients treated with ICT + MIDO compared with patients not receiving MIDO (68% vs. 87.5%, P=0.011). In patients receiving ICT + MIDO, detection of multiple FLT3-ITD clones (referred to as "clonal interference") was associated with a higher FLT3-ITD persistence rate at R/R disease (multiple clones: 88% vs. single clones: 57%, P=0.049). Considering both treatment groups, if only 24% of FLT3-ITD microclones detected at diagnosis were retained at relapse, 43% of them became macroclones. Together, these results identify parameters influencing the fitness of FLT3-ITD clones and highlight the importance of using sensitive techniques for FLT3­-ITD screening in clinical practice.Lire moins >

Langue :

Anglais

Vulgarisation :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL