Venetoclax with azacitidine disrupts energy metabolism and targets leukemia stem cells in patients with acute myeloid leukemia

Menée auprès de 33 patients âgés de 65 à 89 ans et atteints d'une leucémie myéloïde aiguë (âge médian : 75 ans) puis menée in vitro, cette étude montre qu'un traitement combinant vénétoclax et azacitidine perturbe le métabolisme énergétique et cible les cellules souches cancéreuses

Résumé en anglais

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Leukemia stem cells (LSCs) drive the initiation and perpetuation of AML, are quantifiably associated with worse clinical outcomes, and often persist after conventional chemotherapy resulting in relapse1,2,3,4,5. In this report, we show that treatment of older patients with AML with the B cell lymphoma 2 (BCL-2) inhibitor venetoclax in combination with azacitidine results in deep and durable remissions and is superior to conventional treatments. We hypothesized that these promising clinical results were due to targeting LSCs. Analysis of LSCs from patients undergoing treatment with venetoclax + azacitidine showed disruption of the tricarboxylic acid (TCA) cycle manifested by decreased