LSC17 Score Is Complementary with Minimal Residual Disease to Stratify NPM1 -Mutated Acute Myeloid Leukemia: An ALFA Study - Université de Lille Accéder directement au contenu
Article Dans Une Revue Blood Année : 2022

LSC17 Score Is Complementary with Minimal Residual Disease to Stratify NPM1 -Mutated Acute Myeloid Leukemia: An ALFA Study

Loïc Vasseur
  • Fonction : Auteur
Laurène Fenwarth
  • Fonction : Auteur
Xavier Thomas
  • Fonction : Auteur
Jérôme Lambert
  • Fonction : Auteur
Stéphane de Botton
  • Fonction : Auteur
Céline Villenet
  • Fonction : Auteur
Pierre-Yves Dumas
  • Fonction : Auteur
Christian Recher
  • Fonction : Auteur
Céline Berthon
  • Fonction : Auteur
Emilie Lemasle
  • Fonction : Auteur
Delphine Lebon
Juliette Lambert
  • Fonction : Auteur
Christine Terré
  • Fonction : Auteur
Karine Celli-Lebras
  • Fonction : Auteur
Hervé Dombret
  • Fonction : Auteur
Claude Preudhomme
  • Fonction : Auteur
Meyling Cheok
  • Fonction : Auteur
Raphael Itzykson
  • Fonction : Auteur
Nicolas Duployez
  • Fonction : Auteur

Résumé

Abstract Background In the era of personalized medicine, the establishment of preclinical models of cancer that faithfully recapitulate original tumors is essential to potentially guide clinical decisions. Methods We established 7 models [4 cell lines, 2 Patient-Derived Tumor Organoids (PDTO) and 1 Patient-Derived Xenograft (PDX)], all derived from the same Ovarian Clear Cell Carcinoma (OCCC). To determine the relevance of each of these models, comprehensive characterization was performed based on morphological, histological, and transcriptomic analyses as well as on the evaluation of their response to the treatments received by the patient. These results were compared to the clinical data. Results Only the PDX and PDTO models derived from the patient tumor were able to recapitulate the patient tumor heterogeneity. The patient was refractory to carboplatin, doxorubicin and gemcitabine, while tumor cell lines were sensitive to these treatments. In contrast, PDX and PDTO models displayed resistance to the 3 drugs. The transcriptomic analysis was consistent with these results since the models recapitulating faithfully the clinical response grouped together away from the other classical 2D cell culture models. We next investigated the potential of drugs that have not been used in the patient clinical management and we identified the HDAC inhibitor belinostat as a potential effective treatment based on PDTO response. Conclusions PDX and PDTO appear to be the most relevant models, but only PDTO seem to present all the necessary prerequisites for predictive purposes and could constitute relevant tools for therapeutic decision support in the context of these particularly aggressive cancers refractory to conventional treatments.

Dates et versions

hal-04435064 , version 1 (02-02-2024)

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Citer

Loïc Vasseur, Laurène Fenwarth, Xavier Thomas, Jérôme Lambert, Stéphane de Botton, et al.. LSC17 Score Is Complementary with Minimal Residual Disease to Stratify NPM1 -Mutated Acute Myeloid Leukemia: An ALFA Study. Blood, 2022, 140 (Supplement 1), pp.6303-6305. ⟨10.1182/blood-2022-163348⟩. ⟨hal-04435064⟩
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