Article Dans Une Revue Briefings in Bioinformatics Année : 2024

Predictive modelling of acute Promyelocytic leukaemia resistance to retinoic acid therapy

Résumé

Acute Promyelocytic Leukaemia (APL) arises from an aberrant chromosomal translocation involving the Retinoic Acid Receptor Alpha (RARA) gene, predominantly with the Promyelocytic Leukaemia (PML) or Promyelocytic Leukaemia Zinc Finger (PLZF) genes. The resulting oncoproteins block the haematopoietic differentiation program promoting aberrant proliferative promyelocytes. Retinoic Acid (RA) therapy is successful in most of the PML::RARA patients, while PLZF::RARA patients frequently become resistant and relapse. Recent studies pointed to various underlying molecular components, but their precise contributions remain to be deciphered. We developed a logical network model integrating signalling, transcriptional, and epigenetic regulatory mechanisms, which captures key features of the APL cell responses to RA depending on the genetic background. The explicit inclusion of the histone methyltransferase EZH2 allowed the assessment of its role in the resistance mechanism, distinguishing between its canonical and non-canonical activities. The model dynamics was thoroughly analysed using tools integrated in the public software suite maintained by the CoLoMoTo consortium (https:// colomoto.github.io/). The model serves as a solid basis to assess the roles of novel regulatory mechanisms, as well as to explore novel therapeutical approaches in silico.

Fichier principal
Vignette du fichier
sanchez-villanueva25a.pdf (1.75 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte
licence

Dates et versions

hal-04905666 , version 1 (22-01-2025)

Licence

Identifiants

Citer

José A Sánchez-Villanueva, Lia N’guyen, Mathilde Poplineau, Estelle Duprez, Élisabeth Remy, et al.. Predictive modelling of acute Promyelocytic leukaemia resistance to retinoic acid therapy. Briefings in Bioinformatics, 2024, 26 (1), ⟨10.1093/bib/bbaf002⟩. ⟨hal-04905666⟩
0 Consultations
0 Téléchargements

Altmetric

Partager

More