Chlorinated adenosine analogue induces AMPK and autophagy in chronic lymphocytic leukaemia cells during therapy

Christine M. Stellrecht, Lisa S. Chen, Mary L. Ayres, Jennifer B. Dennison, Shujun Shentu, Yuling Chen, Michael J. Keating, William G. Wierda, Varsha Gandhi

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

8-chloro-adenosine (8-Cl-Ado) is currently in phase-I clinical trials for acute myeloid leukaemia and chronic lymphocytic leukaemia (CLL). Previously, we demonstrated that treatment with 8-Cl-Ado leads to diminished ATP levels. We hypothesized that AMP-activated protein kinase (AMPK) signalling would be initiated in these cells, leading to induction of autophagy. AMPK activation and induction of autophagy were demonstrated during preclinical incubations in CLL cells with the analogues. Importantly, we extended similar observations in CLL lymphocytes during an 8-Cl-Ado phase-I trial. In conclusion, 8-Cl-Ado treatment induces autophagy in CLL lymphocytes in vitro as well as in vivo during clinical trial.

Original languageEnglish (US)
Pages (from-to)266-271
Number of pages6
JournalBritish Journal of Haematology
Volume179
Issue number2
DOIs
StatePublished - Oct 2017

Keywords

  • 8-chloro-adenosine
  • AMPK
  • CLL
  • autophagy
  • clinical trial

ASJC Scopus subject areas

  • Hematology

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