Antitumor effects of PRIMA-1 and PRIMA-1met (APR246) in hematological malignancies: Still a mutant p53-dependent affair?

P. Menichini, P. Monti, A. Speciale, G. Cutrona, S. Matis, F. Fais, E. Taiana, A. Neri, R. Bomben, M. Gentile, V. Gattei, M. Ferrarini, F. Morabito, G. Fronza

Research output: Contribution to journalArticlepeer-review


Because of its role in the regulation of the cell cycle, DNA damage response, apoptosis, DNA repair, cell migration, autophagy, and cell metabolism, the TP53 tumor suppressor gene is a key player for cellular homeostasis. TP53 gene is mutated in more than 50% of human cancers, although its overall dysfunction may be even more frequent. TP53 mutations are detected in a lower percentage of hematological malignancies compared to solid tumors, but their frequency generally increases with disease progression, generating adverse effects such as resistance to chemotherapy. Due to the crucial role of P53 in therapy response, several molecules have been developed to re-establish the wild-type P53 function to mutant P53. PRIMA-1 and its methylated form PRIMA-1Met (also named APR246) are capable of restoring the wild-type conformation to mutant P53 and inducing apoptosis in cancer cells; however, they also possess mutant P53-independent properties. This review presents the activities of PRIMA-1 and PRIMA-1Met/APR246 and describes their potential use in hematological malignancies. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Original languageEnglish
Pages (from-to)1-15
Number of pages15
Issue number1
Publication statusPublished - 2021


  • CLL
  • Hematological malignancies
  • Leukemia
  • Mutant P53
  • PRIMA-1/APR246
  • 2 hydroxymethyl 2 methoxymethyl 3 quinuclidinone
  • antineoplastic agent
  • ibrutinib
  • prima 1
  • protein p53
  • unclassified drug
  • venetoclax
  • 2,2-bis(hydroxymethyl)-1-azabicyclo(2,2,2,)octan-3-one
  • fused heterocyclic rings
  • heterocyclic compound
  • acute myeloid leukemia
  • antitumorigenic activity
  • apoptosis
  • cancer chemotherapy
  • cancer growth
  • cell metabolism
  • cell migration
  • chronic lymphatic leukemia
  • conformational transition
  • DNA methylation
  • DNA repair
  • gene expression
  • gene frequency
  • gene mutation
  • genetic transcription
  • hematologic malignancy
  • homeostasis
  • human
  • molecular mechanics
  • multiple myeloma
  • nonhuman
  • oxidative stress
  • phase 3 clinical trial (topic)
  • protein function
  • protein phosphorylation
  • protein structure
  • Review
  • signal transduction
  • animal
  • clinical trial (topic)
  • genetics
  • hematologic disease
  • methylation
  • mutation
  • Animals
  • Antineoplastic Agents
  • Aza Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Clinical Trials as Topic
  • Hematologic Neoplasms
  • Humans
  • Methylation
  • Mutation
  • Tumor Suppressor Protein p53


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