Open AccessSignalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells
Author(s) -
Pereira Olga,
Teixeira Alexandra,
SampaioMarques Belém,
Castro Isabel,
Girão Henrique,
Ludovico Paula
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13737
Subject(s) - autophagy , pi3k/akt/mtor pathway , cancer research , protein kinase b , ampk , biology , myeloid , myeloid leukemia , oxidative phosphorylation , glycolysis , flux (metallurgy) , microbiology and biotechnology , signal transduction , phosphorylation , metabolism , apoptosis , chemistry , endocrinology , biochemistry , protein kinase a , organic chemistry
Acute myeloid leukaemia ( AML ) comprises a heterogeneous group of hematologic neoplasms characterized by diverse combinations of genetic, phenotypic and clinical features representing a major challenge for the development of targeted therapies. Metabolic reprogramming, mainly driven by deregulation of the nutrient‐sensing pathways as AMPK , mTOR and PI 3K/ AKT , has been associated with cancer cells, including AML cells, survival and proliferation. Nevertheless, the role of these metabolic adaptations on the AML pathogenesis is still controversial. In this work, the metabolic status and the respective metabolic networks operating in different AML cells ( NB ‐4, HL ‐60 and KG ‐1) and their impact on autophagy and survival was characterized. Data show that whereas KG ‐1 cells exhibited preferential mitochondrial oxidative phosphorylation metabolism with constitutive co‐activation of AMPK and mTORC 1 associated with increased autophagy, NB ‐4 and HL ‐60 cells displayed a dependent glycolytic profile mainly associated with AKT / mTORC 1 activation and low autophagy flux. Inhibition of AKT is disclosed as a promising therapeutical target in some scenarios while inhibition of AMPK and mTORC 1 has no major impact on KG ‐1 cells’ survival. The results highlight an exclusive metabolic profile for each tested AML cells and its impact on determination of the anti‐leukaemia efficacy and on personalized combinatory therapy with conventional and targeted agents.