Ceramide nanoliposomes augment the efficacy of venetoclax and cytarabine in models of acute myeloid leukemia

Andrei V. Khokhlatchev, Arati Sharma, Tye G. Deering, Jeremy J.P. Shaw, Pedro Costa-Pinheiro, Upendarrao Golla, Charyguly Annageldiyev, Myles C. Cabot, Mark R. Conaway, Su Fern Tan, Johnson Ung, David J. Feith, Thomas P. Loughran, David F. Claxton, Todd E. Fox, Mark Kester

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Despite several new therapeutic options for acute myeloid leukemia (AML), disease relapse remains a significant challenge. We have previously demonstrated that augmenting ceramides can counter various drug-resistance mechanisms, leading to enhanced cell death in cancer cells and extended survival in animal models. Using a nanoscale delivery system for ceramide (ceramide nanoliposomes, CNL), we investigated the effect of CNL within a standard of care venetoclax/cytarabine (Ara-C) regimen. We demonstrate that CNL augmented the efficacy of venetoclax/cytarabine in in vitro, ex vivo, and in vivo models of AML. CNL treatment induced non-apoptotic cytotoxicity, and augmented cell death induced by Ara-C and venetoclax. Mechanistically, CNL reduced both venetoclax (Mcl-1) and cytarabine (Chk1) drug-resistant signaling pathways. Moreover, venetoclax and Ara-C augmented the generation of endogenous pro-death ceramide species, which was intensified with CNL. Taken together, CNL has the potential to be utilized as an adjuvant therapy to improve outcomes, potentially extending survival, in patients with AML.

Original languageEnglish (US)
Article numbere22514
JournalFASEB Journal
Issue number10
StatePublished - Oct 2022

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


Dive into the research topics of 'Ceramide nanoliposomes augment the efficacy of venetoclax and cytarabine in models of acute myeloid leukemia'. Together they form a unique fingerprint.

Cite this