Kevetrin induces apoptosis in TP53 wild-type and mutant acute myeloid leukemia cells

Roberta Napolitano, Serena de Matteis, Silvia Carloni, Samantha Bruno, Giulia Abbati, Laura Capelli, Martina Ghetti, Maria Teresa Bochicchio, Chiara Liverani, Laura Mercatali, Daniele Calistri, Antonio Cuneo, Krishna Menon, Gerardo Musuraca, Giovanni Martinelli, Giorgia Simonetti

Research output: Contribution to journalArticlepeer-review


Tumor protein p53 is a key regulator of several cellular pathways, including DNA repair, cell cycle and angiogenesis. Kevetrin exhibits p53-dependent as well as-independent activity in solid tumors, while its effects on leukemic cells remain unknown. The aim of the present study was to analyze the response of acute myeloid leukemia (AML) cell lines (TP53 wild-type: OCI-AML3 and MOLM-13; and TP53-mutant: KASUMI-1 and NOMO-1) to kevetrin at a concentration range of 85-340 µM. The cellular and molecular effects of the treatment were analyzed in terms of cell growth, viability [Annexin V-propidium iodide (PI) staining] and cell cycle alterations (PI staining). Gene expression profiling, western blotting and immunofluorescence were performed to elucidate the pathways underlying kevetrin activity. Pulsed exposure exerted no effect on the wild-type cells, but was effective on mutant cells. After continuous treatment, significant cell growth arrest and apoptosis were observed in all cell lines, with TP53-mutant models displaying a higher sensitivity and p53 induction. Kevetrin also displayed efficacy against TP53 wild-type and mutant primary AML, with a preferential cytotoxic activity against blast cells. Gene expression profiling revealed a common core transcriptional program altered by drug exposure and the downregulation of glycolysis, DNA repair and unfolded protein response signatures. These findings suggest that kevetrin may be a promising therapeutic option for patients with both wild-type and TP53-mutant AML.

Original languageEnglish
Pages (from-to)1561-1573
Number of pages13
JournalOncology Reports
Issue number4
Publication statusPublished - Oct 2020


  • Acute myeloid leukemia
  • Apoptosis
  • Gene expression profiling
  • Kevetrin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Kevetrin induces apoptosis in TP53 wild-type and mutant acute myeloid leukemia cells'. Together they form a unique fingerprint.

Cite this