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Chlorinated adenosine analogue induces AMPK and autophagy in chronic lymphocytic leukaemia cells during therapy
Author(s) -
Stellrecht Christine M.,
Chen Lisa S.,
Ayres Mary L.,
Dennison Jennifer B.,
Shentu Shujun,
Chen Yuling,
Keating Michael J.,
Wierda William G.,
Gandhi Varsha
Publication year - 2017
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14859
Subject(s) - autophagy , ampk , adenosine , medicine , in vitro , cancer research , protein kinase a , in vivo , chronic lymphocytic leukemia , immunology , pharmacology , kinase , biology , leukemia , microbiology and biotechnology , biochemistry , apoptosis
Summary 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.